- Email: [email protected]
The Age-Dependent Neural Substrates of Blindsight
TINS 1577 No. of Pages 11
Trends in Neurosciences
Review
The Age-Dependent Neural Substrates of Blindsight Dylan M. Fox,1 Melvyn A. Goodale,2 and James A. Bourne
1,
*
Some patients who are considered cortically blind due to the loss of their primary visual cortex (V1) show a remarkable ability to act upon or discriminate between visual stimuli presented to their blind field, without any awareness of those stimuli. This phenomenon is often referred to as blindsight. Despite the range of spared visual abilities, the identification of the pathways mediating blindsight remains an active and contentious topic in the field. In this review, we discuss recent findings of the candidate pathways and their relative contributions to different forms of blindsight across the lifespan to illustrate the varied nature of unconscious visual processing.
Highlights
Blindsight and Its Origins
There is emerging evidence that the pulvinar is heavily involved in acquisition of early-life blindsight due to its crucial role in visual cortical development.
The relative contributions of retinorecipient nuclei in mediating blindsight-like behaviours is highly controversial. While several studies have elucidated the clear involvement of the lateral geniculate nucleus, others have also shown strong pulvinar influences through direct retinal pathways and through collicular projections.
Damage to the primary visual cortex (V1, striate cortex) in humans typically leads to discrete regions of ‘cortical’ blindness, scotoma (see Glossary), within which conscious visual awareness is abolished. Remarkably, however, a number of these patients show spared visually driven behaviour in their scotoma, despite the vigorous denial of any conscious visual experience [1,2]. The presence of unconscious vision in these otherwise ‘blind’ patients has been termed ‘blindsight’ [2]. The spared visual abilities observed in blindsight vary across a broad range of behaviours, including visually guided actions, such as: pointing towards or grasping an object and navigating obstacles; discriminating amongst emotional signals expressed on faces [3–5]; as well as a number of cognitive processes such as attention [6] and spatial memory [7]. Identifying the neural substrates supporting the array of residual abilities observed across blindsight patients continues to challenge the research community and there are divided opinions as to the pathways that might be involved. It is likely that blindsight is not a unitary phenomenon but instead reflects the engagement of multiple pathways from the eye to the brain, many of which do not project towards V1 [8,9]. Understanding the role of specific circuits that can contribute to blindsight, and what factors are crucial in determining the extent of visual preservation observed, is a critical question in visual neuroscience. Such information could not only provide valuable insights into how the visual system remodels itself following injury but could also provide a better understanding of how changes in neural activity can modulate our perceptual experience. Here we review how recent cases of blindsight in humans and experimental models in non-human primates have reshaped our understanding of the potential neural substrates mediating preserved visual function. We then examine the candidate pathways proposed for facilitating blindsight abilities and discuss how recent findings point towards the relative contribution of specific pathways being largely determined by the age at which the V1 lesion was acquired. Finally, we ask, to what extent these pathways are hardwired and how they can change across the lifespan.
The Spectrum of Blindsight An additional complication to blindsight cases is that it can present in various forms. This relates to both the reported phenomenology of the patient and the nature of the spared visual capacities. One of the earliest distinctions to be made was between spared visual abilities unaccompanied by any conscious experience (type I blindsight) and those in which the patient reports some form of Trends in Neurosciences, Month 2020, Vol. xx, No. xx
Due to the presence of a broad range of preserved behavioural capacities in blindsight patients, there has been a shift away from identifying a unitary neural substrate. Instead, blindsight is thought to operate through multiple functional groups, with each group preserving an element of unconscious visual function, such as the sensitivity to motion direction.
1
Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia 2 The Brain and Mind Institute, The University of Western Ontario, Western Interdisciplinary Research Building, London, Ontario, Canada
*Correspondence: [email protected] (J.A. Bourne).
https://doi.org/10.1016/j.tins.2020.01.007 © 2020 Elsevier Ltd. All rights reserved.
1
Trends in Neurosciences
awareness (a ‘feeling’ or an intuition), but an experience that is not visual in nature (type II blindsight) [10]. Whether these are distinct categories or simply the opposite ends of a continuous distribution of awareness remains a matter of some debate (Box 1). In any case, the presence of some nonvisual awareness in type II blindsight has challenged theories surrounding the role of V1 in conscious awareness [11]. The nature of the experience reported by patients with type II blindsight remains controversial: is it simply a form of degraded vision or a nonvisual form of conscious awareness? [12,13]. In both types of blindsight, measurements of sympathetic activation such as pupil dilation and skin conductance have been observed during passive viewing of particular kinds of visual stimuli (such as fearful or happy faces) presented in the patients’ blind field [14], indicating shared unconscious visual processing. Other distinctions have been made, not in terms of the nature of the phenomenology in blindsight, but rather in terms of the spared visual abilities. Thus, some patients, whether they have type I or type II blindsight, can preshape and orient their hand in flight to match the dimensions and orientation of a target object when they reach out to grasp it, even though they are unable to report the object’s shape, dimensions, or orientation [15,16]. This residual ability has been termed ‘action blindsight’ [17]. Other patients exhibit covert shifts of attention and aspects of spatial orienting in the absence of any visual experience. This particular sensitivity to unseen visual stimuli has been described as ‘attention blindsight’ [17]. It could be argued that action blindsight requires attention blindsight; that is, patients must attend to the objects they are grasping. Some patients with cortical blindness can discriminate between different visual stimuli based on their form, hue, or motion, again, without any visual awareness of those properties. A special category of residual visual discrimination ability, in which patients with damage to V1 can discriminate between fearful, happy, and neutral facial expressions, without visual awareness, has been termed ‘affective blindsight’ [5,18]. Table 1 describes three of the most well-studied patients exhibiting blindsight and highlights the significant overlap between each of the abilities preserved. This brief review of some of the spared visual abilities that have been identified in blindsight almost certainly does not capture all the residual visual behaviour that is present in patients who have lost conscious vision after damage to V1. Moreover, the distinctions that have been made amongst different kinds of spared visually driven behaviour are unlikely to be hard and fast [19,20]. There Box 1. Modelling Consciousness to Different Types of Blindsight The degree of conscious access to visual stimuli presented within the scotoma of type I and type II blindsight patients remains a deeply rooted question in the psychophysical and philosophical literature. Blindsight represents visually driven behaviour in the absence of visual awareness. The presence of type II blindsight in some patients indeed suggests that V1 may not be required for conscious awareness. The two main models of consciousness that have been applied to blindsight cases to explain their paradoxical abilities are the workspace model and the phenomenological model. In the neuronal workspace model [80], consciousness is characterised by global processing throughout the entire brain by a series of modular circuits running in parallel. For a stimulus to reach conscious awareness, it must first be processed by unique workspace neurons that broadcast stimulus-relevant information to subsystems such as the visual sensory modality for motion stimuli. Workspace neurons are regulated in the volume and bandwidth of the information they process, which governs vital aspects of consciousness; its transient nature as seen in visual attention and its seamless nature (i.e., we perceive sensory information from different modalities as a single bound event rather than isolated events of visual, olfactory, and auditory experiences). It is believed that these workspace neurons are a part of the fronto-parietal attention network and are involved in selecting information in the occipital-temporal systems. In blindsight patients without the V1 subsystem, their altered workspace could result in changes to the transmission of information, resulting in perception somewhere between full consciousness and complete absence. In the phenomenological model [81], phenomenal consciousness is supported by repeated activity between two regions. For example, it is possible to have a phenomenal sense of motion when motion-selective cortex (area MT) and primary visual cortex (V1) enter a feedforward and feedback relationship. With the loss of this local recurrent activity in blindsight patients, area MT enters a different activation state between subcortical afferents such as the pulvinar or LGN and this could explain the blindsight spectrum of phenomenal awareness.
2
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
Glossary Blindsight: the ability to respond to visual stimuli presented into a patient’s blind field without the patient consciously perceiving them. This is often observed following damage to the primary visual cortex (V1). Extrastriate cortex: multiple visual association areas that extend beyond V1, each of which process specific elements of visual input but are strongly driven by their input from V1 in the uninjured brain. This includes V2 and V3, which have also been classified as ‘early’ visual areas. Lateral geniculate nucleus (LGN): a small, highly laminated nucleus of the thalamus parcellating visual signals from both eyes into three types of distinctive layers. Magno- and parvocellular layers comprise the main layers, being interleaved with koniocellular layers (K layers). The information, transmitted through the optic tract to the different layers of the LGN, is parcellated based on specific retinal ganglion cell input and thus visual properties. The parvocellular layers of the LGN receive information about colour and form, whereas the magnocellular layers receive information about motion and contrast sensitivity. The koniocellular layers receive a diverse mix of retinal inputs that tend to reflect the properties of inputs to adjacent parvo- or magnocellular layers. Middle temporal area (area MT/V5): a region of extrastriate cortex containing direction-selective neurons. Area MT participates in motion perception and is flanked by several satellite regions that collectively integrate motion signals to generate a global motion percept. These signals can then be relayed to higherorder visual areas to help guide visual behaviour. Area MT is also believed to be an important component in the development and maturation of the visual cortex, acting in some ways akin to V1. Pulvinar nuclei: the largest collection of thalamic nuclei (in primates) occupying the posterior pole of the thalamus. The nuclei of the pulvinar involved in vision are the inferior (PI) and lateral (PL) aspects, each of which have further subnuclei. They play a role in relaying retinal information to the cortex during development, handling cognitive processes such as spatial attention, and integrating cortical and subcortical visual signals. Saccade: a rapid, simultaneous movement of both eyes towards a particular region in the visual field.
Trends in Neurosciences
is the added difficulty of generalising findings from the observed behaviour in blindsight patients to related behaviour in the neurologically healthy individuals due to the genuine possibility of altered connectivity after brain damage. Indeed, since blindsight is not observed in all patients with V1 damage, it may be the case that blindsight is the result of modified neuronal connections rather than reflecting the inherent function of an intact brain. What is clear is that the pathways that have been implicated in blindsight are far less prominent than the geniculo-striate pathway in the neurologically intact visual system and the role of these pathways in mediating the range of residual visual abilities described above remains contentious. In the following section, we review the evidence for the putative pathways that have been proposed.
Candidate Substrates of Blindsight The pathways that have been proposed to support blindsight have included entirely subcortical routes from the eye to effectors, as well as pathways to extrastriate visual areas in the cerebral cortex that bypass the main geniculo-striate pathway. Also, it has been argued that some of these pathways, particularly those engaging the cerebral cortex, may have been rewired after damage to V1, mainly in cases where the damage occurred early in life. The presence of alternative pathways to the extrastriate cortex and their putative role in supporting blindsight have been extensively studied. Connectional and behavioural findings in non-human primates and imaging studies in patients with V1 damage have revealed a number of pathways (Figure 1A) that could support spared visual behaviour thought to be mediated by extrastriate areas [9,21,22]. Two pathways, one involving the koniocellular layers (K layers) of the lateral geniculate nucleus (LGN) and the other the pulvinar nuclei, have traditionally been identified as the most likely candidates [23–26]. Here, we summarise the evidence for each of these pathways from studies in non-human primates and consider to what extent these pathways can facilitate blindsight and what abilities are likely to be preserved. An anatomical feature the two pathways share is that both project to the visual middle temporal (MT) cortical area and its satellites, key cortical areas associated with the dorsal stream. Finally, we will consider other retinorecipient nuclei that have not been examined in recent years (Figure 2). If blindsight is indeed a modular phenomenon, we believe that the study of these areas could provide valuable insights into some aspects of the unconscious processing of visual information.
Saccades are believed to be controlled both cortically, by the frontal eye fields as well as areas in the posterior parietal cortex, and subcortically by the superior colliculus. Saccades are essential for changing fixation and attending to a stimulus. Scotoma: a localised region of blindness, or blind spot in the visual field. Specifically, it is an area of diminished/ absent visual acuity, which generally juxtaposes a region of normal vision. Although each mammalian eye has a scotoma due to the optic nerve head, the term is generally used in cases of altered vision. A scotoma typically arises from damage to the retina, V1, or the pathways from the retina to V1. Superior colliculus (SC): a laminated midbrain structure comprising (in primates) seven layers subdivided into three functional zones. The three superficial layers are retinorecipient; the two intermediate layers represent the integration of multiple sensory modalities, whereas the final two deep layers are motor-related, involved in the initiation of eye movements. Overall, the SC receives direct retinal information to guide saccades towards salient regions.
The Central Role of Area MT Specific retinorecipient subcortical pathways project directly to the middle temporal area (area MT/V5). This includes the LGN, via the K layers [21,27,28], the medial portion of the inferior pulvinar (PIm) [28,29], or indirectly via the superior colliculus (SC) to the remaining divisions of the inferior Table 1. List of Well-Studied Patients for Various Abilities Observed in Blindsight Patient
Nature and timing of injury
Action blindsight tested
Affective blindsight tested
Other abilities tested
T.N.
Adult-acquired (aged 52 years); bilateral V1 loss resulting from two consecutive strokes with a 36-day interval
Locomotion/navigation [83]
Emotional facial expression discrimination [84] at low spatial frequencies [3]
Visual mental imagery [86]
D.B.
Adult acquired; surgical ablation of right medial occipital lobe due to an arterious venus malformation
Pointing, spatial localization [2]
Emotional valence discrimination [14]
Detection and discrimination (orientation, motion direction, and form) [88]
G.Y.
Early-life acquired (aged ~7–8 years); traumatic brain injury damaged the left medial occipital lobe
Control of hand action [89]
Facial expression discrimination [18] with strengthened pathways between the pulvinar and amygdala [45]
Colour and motion discrimination, but not brightness [91]
Spatial orienting [90]
Emotional valence discrimination [14]
Amygdala response patterns to eye contact [85]
Categorical processing of visual stimuli [87]
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
3
Trends in Neurosciences
Trends in Neurosciences
Figure 1. Putative Subcortical Pathways Facilitating Blindsight. (A) Medial view schematic showing feedforward pathways travelling from the retina to extrastriate cortex in the PPC. Opaque pathways indicate neuronal degeneration as a result of V1 injury. (B,C) Proposed subcortical pathways for facilitating blindsight capacity following V1 injury in the developing brain (B) and the adult brain (C). Line thickness indicates the strength or relative density of the projection. Brain schematic in (A) generated using BioRender. Abbreviations: Amg, Amygdala; LGN, lateral geniculate nucleus; MT, middle temporal area; PI, inferior pulvinar; PIcl, caudolateral division of inferior pulvinar; PIcm, centromedial division of inferior pulvinar; PIm, medial division of inferior pulvinar; PIp, posterior division of inferior pulvinar; PPC, posterior parietal cortex; Pul, pulvinar; SC, superior colliculus.
pulvinar (PI) [30–32]. Although these pathways are well-mapped in the adult brain and convincingly reveal the central involvement of area MT, there remains controversy concerning which pathway plays the most prominent role in blindsight. Furthermore, the role of these pathways during development both in the intact brain and following V1 injury requires further investigation to elucidate their involvement in driving area MT activity. Finally, it is worth noting that it is likely that the projections from the K layers mediate spared visual abilities that are distinct from those mediated by projections from the pulvinar. Area MT in the developing brain shares many properties with V1 with respect to its cellular maturation patterns and dense myelination at birth, suggesting that it should be considered a 4
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
Trends in Neurosciences
Trends in Neurosciences
Figure 2. Retinorecipient Nuclei. Schematic showing all known retinal projections (in primates) grouped by region or functional system. Their broad functions are listed for each group. Subsequent feedforward and feedback projections are not shown. Abbreviations: AOS, Accessory optic system; LGN, lateral geniculate nucleus; M/D/LTN, medial/dorsal/lateral terminal nuclei; NOT, nucleus of the optic tract; OPN, olivary pretectal nucleus; PI, inferior pulvinar; PN, pretectal nuclei (including anterior, medial, and dorsal); PrG, pregeniculate nucleus; SC, superior colliculus; SCN, suprachiasmatic nucleus.
‘primary-like’ area [33,34]. Indeed, the strong presence of area MT within the developing brain makes it a prime candidate for facilitating visual input in the absence of V1 (see Box 2 for theories surrounding its early development). Despite the presence of robust V1 inputs to area MT in the adult brain [35], this connection is not fully established early in life [33,34], suggesting that the timing of a lesion to V1 could be a contributing factor to the degree of preserved residual vision. This conclusion has been supported by the fact that MT neurons continue to show vigorous activity after lesions of V1 in the developing brain [36–38]. Conversely, if the V1 injury occurs later in life, the typical responses of MT neurons are mostly attenuated [36] and instead their activity for motion [39] and contrast [40] sensitivity resembles the response patterns observed in V1 of neurologically intact individuals. Although these findings show that normal area MT activity relies on V1 input, they also illustrate how area MT can be reshaped during adulthood by putative subcortical pathways to mimic V1 activity at the expense of its normal functioning. Pulvinar Nuclei In recent years, a greater appreciation has emerged for the involvement of pulvinar nuclei in driving the development of area MT [29,41,42], specifically the PIm, and this thalamic nucleus is now a leading candidate for mediating the residual visual abilities in blindsight (Figure 1B). Pulvinar involvement in blindsight was traditionally thought to operate in conjunction with the collicular pathways, mediating visual attention by integrating eye movements with salient stimuli. PIm receives direct retinal input [28,29,43], expanding its possible role in mediating a range of
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
5
Trends in Neurosciences
Box 2. Hierarchical and Mosaic Patterns of Visual Development While the shared activity of the visual cortex enables our visual experience, it is comprised of multiple areas, each with their own unique connectivity and function. Understanding the mode of development can lead to inferences on which visual abilities would be likely to appear first. It was traditionally believed that the visual cortex develops in a hierarchical pattern, emanating from the early developed primary visual area (V1) to higher-order areas in a wave-like pattern. From V1, the wave bifurcated down two ‘streams’: a dorsal stream, handling spatial awareness and visually guided actions in the posterior parietal cortex, and a ventral stream, processing declarative information such as facial discrimination in the inferior temporal areas [82]. New lines of evidence have suggested that this proposed model of hierarchical development from the V1 hub may not progress in a strictly linear manner. Area MT, an extrastriate region involved in global motion processing, has been shown to develop and mature in parallel to V1 and other primary sensory modalities as evidenced by its dense myelination at birth and presence of mature pyramidal cells early in life [33,41]. Instead, it has been proposed that development may occur in a mosaic pattern, with large hubs such as V1 and area MT serving as developmental drivers of extrastriate cortex [34]. While the two streams are also present in the mosaic model of visual development, they develop asynchronously, which is likely due to the substantial driver input from area MT primarily to the dorsal-stream network. The afferent pathways providing visual input to area MT early in life are likely sourced from transient retino-pulvino projections that peak during development.
blindsight abilities (Figure 1). Specifically, it explains how area MT could receive instructive subcortical input during development, thereby strengthening dorsal-stream activity to visual stimuli before V1 input to MT is fully established. This has been supported by observations that the pulvinar is necessary for maintaining area MT activation by motion stimuli [44]. Furthermore, pulvinar afferents to MT outnumber V1 afferents early in life [29]. With the widespread connectivity of the pulvinar with both subcortical and cortical areas, it is ideally positioned to be involved in several abilities that can be preserved in blindsight patients. In an exclusively subcortical route, the interactions between the SC, pulvinar, and the amygdala have been considered essential for the mediation of affective blindsight in both humans [45] and monkeys [46]. Such cases involve individuals being able to correctly discriminate emotional stimuli presented within their blind field, for example, distinguishing between happy and fearful faces that are presented in a forced-choice manner [47]. These findings support the notion of an unconscious visual pathway that can extract affective features from facial expressions without input from higher-order areas of the ventral visual stream, involved in face and object recognition, in addition to the absence of V1 input [3–5]. Lateral Geniculate Nucleus Of interest, the interleaving K layers of the LGN [47] represent the V1-independent pathway to extrastriate cortex displaying sparse projections to area MT [27,48]. These K layers also receive visual information from the superficial visual layers of the SC [49]. This geniculo-extrastriate pathway has been widely studied, with substantial evidence demonstrating its involvement in adult blindsight patients (Figure 1C). Injuries to V1 trigger substantial retrograde degeneration of the optic radiations and, ultimately, the corresponding retinotopic region of the LGN [50,51]. The loss of LGN after V1 damage therefore appeared to favour the route from the SC to the pulvinar as the pathway responsible for blindsight abilities. Recently, however, the examination of LGN neurons in the putative K layers that survived V1 lesions at the site of degeneration revealed a viable pathway that remained visually responsive [52]. Although there was clearly degeneration of the main pathways from LGN and V1, projections from the K layers in LGN to area MT [53–55] are capable of contributing to blindsight abilities [56]. Although these tracts are not necessarily strengthened [57], they typically match those of healthy controls, suggesting their importance in maintaining the activation and function of area MT. There is also evidence to suggest that surviving LGN neurons can maintain connections with the extrastriate cortex, including V2, V3, and V4. In the absence of 6
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
Trends in Neurosciences
V1 input in macaques, neuronal responses that were motion-sensitive were found in V4, which could depend on input from K layers in LGN and/or MT [58]. Most of these findings have been explored in adult-acquired injuries of V1 and it remains unclear whether it is a viable pathway for blindsight cases sustained earlier in life. To put it in perspective, however, this pathway is much smaller than the one projecting from the pulvinar (PIm) to MT [59]. Superior Colliculus Although the SC has received less attention in the context of blindsight in recent years, it must not be overlooked. There is mounting evidence indicating its involvement in several cases of blindsight, or at the very least suggesting that its role cannot be categorically ruled out. Retinocollicular information can reach extrastriate cortex by relaying through both the PI [32,60] and the LGN [61], which then relay to MT and/or its satellites. These di-synaptic pathways may provide an extra level of information for extrastriate cortex interfacing sensorimotor input from the SC with the early-level detection of contrast and orientation from the LGN or pulvinar. In unilateral V1-lesioned macaque monkeys, reversible inactivation of the SC to pulvinar pathway resulted in the impairment of visually guided saccades to the blind field [62]. Furthermore, case studies demonstrated that an unconscious response could be induced through the presentation of achromatic stimuli in the blind field, with the response being attenuated if shortwavelength colour stimuli were used (such as purple) [63,64]. It was concluded that these cases likely had involvement of the SC-extrastriate cortex pathway, due to the lack of colour information the SC receives. In adults, the SC may also mediate perceptual organisation in the absence of V1, with one study revealing an increased sensitivity to structured stimuli rather than abstract stimuli presented in the blind field [65]. In addition, because the SC projects directly to premotor neurons in the brainstem, which mediate the control of visually guided saccades, it is highly capable of driving residual function, particularly eye movements, exclusively through subcortical routes. Rehabilitative investigations revealed that targeting multisensory neurons of the SC with audiovisual stimuli could improve visual responsiveness in the blind field across age groups [66]. By sharing connections with both the LGN and pulvinar, the SC may be a likely candidate for supporting blindsight for V1 damage that occurs throughout the lifespan; future studies are required to establish its contributions to blindsight following V1 damage early in life. Other Retinorecipient Nuclei Although the candidate pathways discussed above reflect the primary current viewpoints in the field, other retinorecipient nuclei could be involved (Figure 2). So far, we have discussed pathways that can reach higher-order cortices to mediate complex visually driven responses. In fact, the role of subcortical pathways in mediating reflexive responses to light and corrective postural functions in blindsight are largely uninvestigated. There is scant evidence linking the retinohypothalamic tract, the accessory optic system, or the pregeniculate nucleus of the thalamus (PrG) [67] to blindsight function. Notably, all these nuclei send projections to the SC, and some to the PI, which in turn can project to the extrastriate cortex. Of note, the primate PrG has been shown to modulate the activity of the suprachiasmatic nucleus (SCN) in entraining appropriate circadian rhythms [68], which raises the question of whether circadian-related changes exist in blindsight patients. There has been no investigation to our knowledge of possible disturbances in melatonin levels, sleep, or the response activities of SCN or PrG nuclei in patients with V1 lesions, but it is likely that such changes, if any, will be observed only in patients with bilateral V1 lesions who are completely cortically blind.
Blindsight as a Function of Age Early-Life V1 Injuries Monkeys and humans that receive damage to V1 earlier in life typically exhibit higher levels of residual vision [54,69–71], highlighting the role of the developing brain in the extent of blindsight Trends in Neurosciences, Month 2020, Vol. xx, No. xx
7
Trends in Neurosciences
acquisition. As a recent example, patient B.I., who presented with extensive bilateral V1 damage 2 weeks postnatally due to a rare metabolic disease, displayed exceptional residual visual abilities, many of which were quite conscious, and an increased PI-MT pathway in the left hemisphere [72]. Additionally, there was a recent finding in the marmoset monkey of a prominent early-life pulvino-MT connection [41], and while usually reduced by adulthood, it remains functional following V1 injury. Taken together, these findings highlight the role of the pulvinar in the preserved visual capacity observed in blindsight, but they do not categorically eliminate the contribution of geniculo-extrastriate pathways. The potential of the LGN to facilitate residual information during early life is diminished due to significant transneuronal degeneration of the retinogeniculostriate pathway occurring more rapidly in early life V1 lesions when compared with similar insults acquired during adulthood [50,51,73]. Indeed, repeated exposure to visual stimuli within the blind field of V1 lesioned patients can yield to the rescuing of residual function, presumably through geniculo-extrastriate projections [74]. In a recent functional magnetic resonance imaging study investigating the functional connections projecting to area MT, the LGN-MT pathway in the injured hemisphere exclusively determined whether patients with an adult-acquired V1 lesion would exhibit blindsight abilities, while the evidence for the role of the pulvinar-MT pathway was mixed [75]. Therefore, the putative roles of the LGN and pulvinar projections to area MT appear to be subject to the timing of the V1 lesion, each contributing at different stages of life. One study to date has challenged this hypothesis, finding that the activity of LGN neurons projecting to extrastriate cortex could be sufficiently viable for the preservation of visual function following V1 injury sustained at any age. This study highlights the fact that, despite degeneration in the LGN, the surviving neurons in this area maintain relatively normal properties and may be enough to support some visual information in blindsight patients [52]. There is strong interest in this conjecture, with new studies continuously adding more pieces to the puzzle. Given the rising interest and the emergence of new techniques, questions surrounding the relative involvement of the pulvinar and the LGN during visual cortical injury can potentially be resolved. V1 Injuries in the Mature Brain While the developing brain has a higher capacity to reorganise and restore function after injury when compared with the adult brain, maturation does not abolish the brain’s potential to recover visual function. In adult patients with unilateral V1 damage, one prominent hypothesis is that the processing of information by the intact hemisphere is sufficient for the maintenance of some blindsight capacities. The presence of blindsight in patients with bilateral V1 damage [55,72], however, conflicts with the notion that residual visual function is mediated by the unaffected hemisphere. These opposing findings may represent the fact that separate parallel pathways contribute to the plastic restoration of visual function. For example, if an intact V1 is present in the other hemisphere, it can assume a key role in stimulating extrastriate activity; otherwise subcortical pathways through either the LGN, PI, and SC can facilitate this instead. It has been suggested that one method of investigating the mechanisms of adult blindsight is to create a reversible ‘lesion’ in V1 via transcranial magnetic stimulation (TMS) [76]. In neurologically healthy individuals who received TMS, however, V1 was shown to be necessary for the unconscious (as well as conscious) perception of motion stimuli [77], with feedback from extrastriate regions such as area MT being required for both conscious [78] and unconscious awareness [79]. These findings suggest that the mechanisms of blindsight in patients who suffered V1 lesions as adults might be different from those supporting unconscious motion processing in neurologically intact individuals.
Concluding Remarks and Future Perspectives Advances in functional and connectivity imaging have revealed significant insights into the networks facilitating the preserved visual abilities seen in blindsight patients. As evidence from 8
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
Outstanding Questions What are the relative influences of the LGN, pulvinar, and SC in facilitating blindsight-like behaviours following early- or adult-life V1 injury? Are different residual abilities mediated by different spared visual pathways? To what extent are V1 pathways to extrastriate cortex hardwired to mediate conscious and unconscious visual awareness? What are the functions of the subcortical projections to extrastriate cortex? Can they permit the unconscious processing of visual stimuli such as motion and contrast in the neurologically intact population when V1 input is disrupted via TMS induction? Are specific residual functions such as ‘affective blindsight’ or ‘action blindsight’ mediated by different pathways, or can the visual system remodel existing and residual intact pathways to carry out all these functions? Does the extrastriate cortex respond to unilateral and bilateral V1 injuries similarly? Does the type of injury (e.g., stroke, blunt trauma) dictate the type or level of response? How do V1 lesions acquired during adulthood differ from those acquired in early life, when the brain is maturing? Which pathways are more likely to respond at different injury timings? Can we recapitulate the reorganisation of visual networks observed in early-life injuries in the adult network to facilitate greater preservation of visual function? Can we improve the blindsight capacities of patients over time using rehabilitative methods? Which methods are better suited at recovering the abilities to detect, localise, and discriminate stimuli in complex scenes?
Trends in Neurosciences
case studies and animal models accumulate, we are gaining a better understanding of the critical factors leading to spared visual abilities and how the impact of these factors can change over the lifespan. The future directions central to this field are outlined in the Outstanding Questions, which address the issues surrounding the contribution of different spared pathways to preserved visual abilities at a given time point in the lifespan. Addressing these questions will have significant implications not only for our understanding of the neural underpinnings of blindsight but also for our understanding of the constraints on visual plasticity following an injury at a network level. Once it is better understood how the visual system responds to primary visual cortical injury, one could employ rehabilitative strategies to enhance (or even direct) this process with the ultimate aim of improving residual visual capacity. Acknowledgements D.M.F. is supported by an Australian Government Research Training Program (RTP) Scholarship. J.A.B. is supported by a Senior Research Fellowship support (APP1077677) from the National Health and Medical Research Council (NHMRC). This work was supported by Project Grants from the National Health and Medical Research Council (APP1042893 & APP1138038). The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government. M.A.G.’s research is supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (RGPIN-2017-04-88) and a grant from the Canadian Institute for Advanced Research.
References 1.
2. 3. 4. 5.
6.
7.
8. 9.
10. 11. 12. 13. 14.
15.
16.
17.
Pöppel, E. et al. (1973) Residual visual function after brain wounds involving the central visual pathways in man. Nature 243, 295–296 Weiskrantz, L. et al. (1974) Visual capacity in the hemianopic field following a restricted occipital ablation. Brain 97, 709–728 Burra, N. et al. (2017) Affective blindsight relies on low spatial frequencies. Neuropsychologia 128, 44–49 Celeghin, A. et al. (2015) From affective blindsight to emotional consciousness. Conscious. Cogn. 36, 414–425 Striemer, C.L. et al. (2017) Affective blindsight in the absence of input from face processing regions in occipital-temporal cortex. Neuropsychologia 128, 50–57 Yoshida, M. et al. (2012) Residual attention guidance in blindsight monkeys watching complex natural scenes. Curr. Biol. 22, 1429–1434 Takaura, K. et al. (2011) Neural substrate of spatial memory in the superior colliculus after damage to the primary visual cortex. J. Neurosci. 31, 4233–4241 Danckert, J. and Goodale, M.A. (2000) Blindsight: a conscious route to unconscious vision. Curr. Biol. 10, R64–R67 Tamietto, M. and Morrone, M.C. (2016) Visual plasticity: blindsight bridges anatomy and function in the visual system. Curr. Biol. 26, R70–R73 Weiskrantz, L. (1997) Consciousness lost and found: a neuropsychological exploration, Oxford University Press Leopold, D.A. (2012) Primary visual cortex: awareness and blindsight. Annu. Rev. Neurosci. 35, 91–109 Mazzi, C. et al. (2016) Blind-sight vs. degraded-sight: different measures tell a different story. Front. Psychol. 7 Weiskrantz, L. (2009) Is blindsight just degraded normal vision? Exp. Brain Res. 192, 413–416 Tamietto, M. et al. (2009) Unseen facial and bodily expressions trigger fast emotional reactions. Proc. Natl. Acad. Sci. U. S. A. 106, 17661 Whitwell, R.L. et al. (2011) Grasping the non-conscious: preserved grip scaling to unseen objects for immediate but not delayed grasping following a unilateral lesion to primary visual cortex. Vis. Res. 51, 908–924 Prentiss, E.K. et al. (2018) Spontaneous in-flight accommodation of hand orientation to unseen grasp targets: a case of action blindsight. Cogn. Neuropsychol. 35, 343–351 Danckert, J. and Rossetti, Y. (2005) Blindsight in action: what can the different sub-types of blindsight tell us about the control of visually guided actions? Neurosci. Biobehav. Rev. 29, 1035–1046
18. De Gelder, B. et al. (1999) Non-conscious recognition of affect in the absence of striate cortex. Neuroreport 10, 3759–3763 19. Sahraie, A. et al. (1997) Pattern of neuronal activity associated with conscious and unconscious processing of visual signals. Proc. Natl. Acad. Sci. U. S. A. 94, 9406–9411 20. Weiskrantz, L. et al. (1995) Parameters affecting conscious versus unconscious visual discrimination with damage to the visual cortex (V1). Proc. Natl. Acad. Sci. U. S. A. 92, 6122–6126 21. Bridge, H. et al. (2008) Changes in connectivity after visual cortical brain damage underlie altered visual function. Brain 131, 1433–1444 22. Pavan, A. et al. (2011) Detection of first- and second-order coherent motion in blindsight. Exp. Brain Res. 214, 261–271 23. Cowey, A. (2010) Visual system: how does blindsight arise? Curr. Biol. 20, R702–R704 24. Yoshida, M. (2013) Neural mechanism of blindsight. Brain Nerve 65, 671–677 25. Schmid, M.C. and Maier, A. (2015) To see or not to see thalamo-cortical networks during blindsight and perceptual suppression. Prog. Neurobiol. 126, 36–48 26. Kaas, J. and Baldwin, M. (2019) The evolution of the pulvinar complex in primates and its role in the dorsal and ventral streams of cortical processing. Vision 4, 3 27. Sincich, L.C. et al. (2004) Bypassing V1: a direct geniculate input to area MT. Nat. Neurosci. 7, 1123–1128 28. Warner, C.E. et al. (2010) Retinal afferents synapse with relay cells targeting the middle temporal area in the pulvinar and lateral geniculate nuclei. Front. Neuroanat. 4, 8 29. Kwan, W.C. et al. (2018) Unravelling the subcortical and retinal circuitry of the primate inferior pulvinar. J. Comp. Neurol. 527, 558–576 30. Berman, R.A. and Wurtz, R.H. (2010) Functional identification of a pulvinar path from superior colliculus to cortical area MT. J. Neurosci. 30, 6342–6354 31. Berman, R.A. and Wurtz, R.H. (2008) Exploring the pulvinar path to visual cortex. Prog. Brain Res. 171, 467–473 32. Stepniewska, I. et al. (2000) Projections of the superior colliculus to subdivisions of the inferior pulvinar in New World and Old World monkeys. Vis. Neurosci. 17, 529–549 33. Bourne, J.A. and Rosa, M.G.P. (2006) Hierarchical development of the primate visual cortex, as revealed by neurofilament immunoreactivity: early maturation of the middle temporal area (MT). Cereb. Cortex 16, 405–414 34. Mundinano, I.C. et al. (2015) Mapping the mosaic sequence of primate visual cortical development. Front. Neuroanat. 9, 1–17
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
9
Trends in Neurosciences
35. Nassi, J.J. et al. (2006) The parvocellular LGN provides a robust disynaptic input to the visual motion area MT. Neuron 50, 319–327 36. Girard, P. et al. (1992) Response selectivity of neurons in area MT of the macaque monkey during reversible inactivation of area V1. J. Neurophysiol. 67, 1437–1446 37. Rosa, M.G.P. et al. (2000) Visual responses of neurons in the middle temporal area of New World monkeys after lesions of striate cortex. J. Neurosci. 20, 5552 38. Yu, H.H. et al. (2013) Visually evoked responses in extrastriate area MT after lesions of striate cortex in early life. J. Neurosci. 33, 12479–12489 39. Ajina, S. et al. (2015) Motion area V5/MT+ response to global motion in the absence of V1 resembles early visual cortex. Brain 138, 164–178 40. Ajina, S. et al. (2015) Abnormal contrast responses in the extrastriate cortex of blindsight patients. J. Neurosci. 35, 8201–8213 41. Warner, C.E. et al. (2012) The early maturation of visual cortical area MT is dependent on input from the retinorecipient medial portion of the inferior pulvinar. J. Neurosci. 32, 17073–17085 42. Mundinano, I-C. et al. (2018) Transient visual pathway critical for normal development of primate grasping behavior. Proc. Natl. Acad. Sci. U. S. A. 115, 1364–1369 43. Cowey, A. et al. (1994) Retinal ganglion cells labelled from the pulvinar nucleus in macaque monkeys. Neuroscience 61, 691–705 44. Barleben, M. et al. (2015) Neural correlates of visual motion processing without awareness in patients with striate cortex and pulvinar lesions. Hum. Brain Mapp. 36, 1585–1594 45. Tamietto, M. et al. (2012) Subcortical connections to human amygdala and changes following destruction of the visual cortex. Curr. Biol. 22, 1449–1455 46. Rafal, R.D. et al. (2015) Connectivity between the superior colliculus and the amygdala in humans and macaque monkeys: virtual dissection with probabilistic DTI tractography. J. Neurophysiol. 114, 1947–1962 47. Gerbella, M. et al. (2017) Pathways for smiling, disgust and fear recognition in blindsight patients. Neuropsychologia 128, 6–13 48. Hendry, S.H.C. and Clay Reid, R. (2000) The koniocellular pathway in primate vision. Annu. Rev. Neurosci. 23, 127–153 49. Zeater, N. et al. (2018) Projections of three subcortical visual centers to marmoset lateral geniculate nucleus. J. Comp. Neurol. 527, 535–545 50. Hendrickson, A. et al. (2015) Retrograde transneuronal degeneration in the retina and lateral geniculate nucleus of the V1lesioned marmoset monkey. Brain Struct. Funct. 220, 351–360 51. Atapour, N. et al. (2017) Neuronal degeneration in the dorsal lateral geniculate nucleus following lesions of primary visual cortex: comparison of young adult and geriatric marmoset monkeys. Brain Struct. Funct. 222, 3283–3293 52. Yu, H-H. et al. (2018) Robust visual responses and normal retinotopy in primate lateral geniculate nucleus following longterm lesions of striate cortex. J. Neurosci. 38, 3955–3970 53. Bridge, H. et al. (2010) Visual activation of extra-striate cortex in the absence of V1 activation. Neuropsychologia 48, 4148–4154 54. Ajina, S. et al. (2015) Human blindsight is mediated by an intact geniculo-extrastriate pathway. Elife 4, e08935 55. Ajina, S. and Bridge, H. (2019) Subcortical pathways to extrastriate visual cortex underlie residual vision following bilateral damage to V1. Neuropsychologia 128, 140–149 56. Schmid, M. et al. (2010) Blindsight depends on the lateral geniculate nucleus. Nature 466, 373–377 57. Bridge, H. et al. (2018) Intact extrastriate visual network without primary visual cortex in a rhesus macaque with naturally occurring blindsight. bioRxiv Published online October 18, 2018. https://doi.org/10.1101/447482 58. Schmid, M.C. et al. (2013) Motion-sensitive responses in visual area V4 in the absence of primary visual cortex. J. Neurosci. 33, 18740–18745 59. Mundinano, I-C. et al. (2019) Retinotopic specializations of cortical and thalamic inputs to area MT. Proc. Natl. Acad. Sci. U. S. A. 116, 201909799 60. Baldwin, M.K.L. et al. (2013) Projections of the superior colliculus to the pulvinar in prosimian galagos (Otolemur garnettii) and
10
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
61.
62.
63. 64.
65.
66.
67.
68.
69.
70.
71.
72.
73.
74.
75.
76.
77.
78.
79.
80.
81. 82. 83. 84.
85.
VGLUT2 staining of the visual pulvinar. J. Comp. Neurol. 521, 1664–1682 Harting, J.K. et al. (1991) Projection of the mammalian superior colliculus upon the dorsal lateral geniculate nucleus: organization of tectogeniculate pathways in nineteen species. J. Comp. Neurol. 304, 275–306 Kinoshita, M. et al. (2019) Dissecting the circuit for blindsight to reveal the critical role of pulvinar and superior colliculus. Nat. Commun. 10, 135 Tamietto, M. et al. (2010) Collicular vision guides nonconscious behavior. J. Cogn. Neurosci. 22, 888–902 Leh, S.E. et al. (2010) Blindsight mediated by an S-cone-independent collicular pathway: an fMRI study in hemispherectomized subjects. J. Cogn. Neurosci. 22, 670–682 Georgy, L. et al. (2016) The superior colliculus is sensitive to gestalt-like stimulus configuration in hemispherectomy patients. Cortex 81, 151–161 Tinelli, F. et al. (2015) Audio-visual stimulation improves visual search abilities in hemianopia due to childhood acquired brain lesions. Multisens. Res. 28, 153–171 Cowey, A. et al. (2001) The retinal projection to the pregeniculate nucleus in normal and destriate monkeys. Eur. J. Neurosci. 13, 279–290 Lima, R.R. et al. (2012) Retinal projections and neurochemical characterization of the pregeniculate nucleus of the common marmoset (Callithrix jacchus). J. Chem. Neuroanat. 44, 34–44 Gross, C.G. et al. (2004) Visually guided behavior after V1 lesions in young and adult monkeys and its relation to blindsight in humans. Prog. Brain Res. 144, 279–294 Moore, T. et al. (1996) Greater residual vision in monkeys after striate cortex damage in infancy. J. Neurophysiol. 76, 3928–3933 Werth, R. (2006) Visual functions without the occipital lobe or after cerebral hemispherectomy in infancy. Eur. J. Neurosci. 24, 2932–2944 Mundinano, I-C. et al. (2017) More than blindsight: case report of a child with extraordinary visual capacity following perinatal bilateral occipital lobe injury. Neuropsychologia 128, 178–186 Cowey, A. et al. (2011) Transneuronal retrograde degeneration of retinal ganglion cells and optic tract in hemianopic monkeys and humans. Brain 134, 2149–2157 Sahraie, A. et al. (2013) The continuum of detection and awareness of visual stimuli within the blindfield: from blindsight to the sighted-sight. Invest. Ophthalmol. Vis. Sci. 54, 3579–3585 Ajina, S. and Bridge, H. (2018) Blindsight relies on a functional connection between hMT+ and the lateral geniculate nucleus, not the pulvinar. PLoS Biol. 16, e2005769 Ro, T. and Rafal, R. (2006) Visual restoration in cortical blindness: insights from natural and TMS-induced blindsight. Neuropsychol. Rehabil. 16, 377–396 Hurme, M. et al. (2019) V1 activity during feedforward and early feedback processing is necessary for both conscious and unconscious motion perception. NeuroImage 185, 313–321 Hurme, M. et al. (2017) Early processing in primary visual cortex is necessary for conscious and unconscious vision while late processing is necessary only for conscious vision in neurologically healthy humans. NeuroImage 150, 230–238 Koivisto, M. et al. (2010) The role of early visual cortex (V1/V2) in conscious and unconscious visual perception. NeuroImage 51, 828–834 Dehaene, S. and Naccache, L. (2001) Towards a cognitive neuroscience of consciousness: basic evidence and a workspace framework. Cognition 79, 1–37 Block, N. (1995) On a confusion about a function of consciousness. Behav. Brain Sci. 18, 227–247 Goodale, M.A. and Milner, A.D. (1992) Separate visual pathways for perception and action. Trends Neurosci. 15, 20–25 de Gelder, B. et al. (2008) Intact navigation skills after bilateral loss of striate cortex. Curr. Biol. 18, R1128–R1129 Pegna, A.J. et al. (2005) Discriminating emotional faces without primary visual cortices involves the right amygdala. Nat. Neurosci. 8, 24–25 Burra, N. et al. (2013) Amygdala activation for eye contact despite complete cortical blindness. J. Neurosci. 33, 10483
Trends in Neurosciences
86. de Gelder, B. et al. (2015) Visual imagery influences brain responses to visual stimulation in bilateral cortical blindness. Cortex 72, 15–26 87. Van den Stock, J. et al. (2014) Neural correlates of body and face perception following bilateral destruction of the primary visual cortices. Front. Behav. Neurosci. 8 88. Trevethan, C.T. et al. (2007) Form discrimination in a case of blindsight. Neuropsychologia 45, 2092–2103
89. Jackson, S.R. (1999) Pathological perceptual completion in hemianopia extends to the control of reach-to-grasp movements. Neuroreport 10, 2461–2466 90. Kentridge, R.W. et al. (1999) Attention without awareness in blindsight. Proc. R. Soc. B Biol. Sci. 266, 1805–1811 91. Morland, A.B. et al. (1999) Visual perception of motion, luminance and colour in a human hemianope. Brain 122, 1183–1198
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
11
Trends in Neurosciences
Review
The Age-Dependent Neural Substrates of Blindsight Dylan M. Fox,1 Melvyn A. Goodale,2 and James A. Bourne
1,
*
Some patients who are considered cortically blind due to the loss of their primary visual cortex (V1) show a remarkable ability to act upon or discriminate between visual stimuli presented to their blind field, without any awareness of those stimuli. This phenomenon is often referred to as blindsight. Despite the range of spared visual abilities, the identification of the pathways mediating blindsight remains an active and contentious topic in the field. In this review, we discuss recent findings of the candidate pathways and their relative contributions to different forms of blindsight across the lifespan to illustrate the varied nature of unconscious visual processing.
Highlights
Blindsight and Its Origins
There is emerging evidence that the pulvinar is heavily involved in acquisition of early-life blindsight due to its crucial role in visual cortical development.
The relative contributions of retinorecipient nuclei in mediating blindsight-like behaviours is highly controversial. While several studies have elucidated the clear involvement of the lateral geniculate nucleus, others have also shown strong pulvinar influences through direct retinal pathways and through collicular projections.
Damage to the primary visual cortex (V1, striate cortex) in humans typically leads to discrete regions of ‘cortical’ blindness, scotoma (see Glossary), within which conscious visual awareness is abolished. Remarkably, however, a number of these patients show spared visually driven behaviour in their scotoma, despite the vigorous denial of any conscious visual experience [1,2]. The presence of unconscious vision in these otherwise ‘blind’ patients has been termed ‘blindsight’ [2]. The spared visual abilities observed in blindsight vary across a broad range of behaviours, including visually guided actions, such as: pointing towards or grasping an object and navigating obstacles; discriminating amongst emotional signals expressed on faces [3–5]; as well as a number of cognitive processes such as attention [6] and spatial memory [7]. Identifying the neural substrates supporting the array of residual abilities observed across blindsight patients continues to challenge the research community and there are divided opinions as to the pathways that might be involved. It is likely that blindsight is not a unitary phenomenon but instead reflects the engagement of multiple pathways from the eye to the brain, many of which do not project towards V1 [8,9]. Understanding the role of specific circuits that can contribute to blindsight, and what factors are crucial in determining the extent of visual preservation observed, is a critical question in visual neuroscience. Such information could not only provide valuable insights into how the visual system remodels itself following injury but could also provide a better understanding of how changes in neural activity can modulate our perceptual experience. Here we review how recent cases of blindsight in humans and experimental models in non-human primates have reshaped our understanding of the potential neural substrates mediating preserved visual function. We then examine the candidate pathways proposed for facilitating blindsight abilities and discuss how recent findings point towards the relative contribution of specific pathways being largely determined by the age at which the V1 lesion was acquired. Finally, we ask, to what extent these pathways are hardwired and how they can change across the lifespan.
The Spectrum of Blindsight An additional complication to blindsight cases is that it can present in various forms. This relates to both the reported phenomenology of the patient and the nature of the spared visual capacities. One of the earliest distinctions to be made was between spared visual abilities unaccompanied by any conscious experience (type I blindsight) and those in which the patient reports some form of Trends in Neurosciences, Month 2020, Vol. xx, No. xx
Due to the presence of a broad range of preserved behavioural capacities in blindsight patients, there has been a shift away from identifying a unitary neural substrate. Instead, blindsight is thought to operate through multiple functional groups, with each group preserving an element of unconscious visual function, such as the sensitivity to motion direction.
1
Australian Regenerative Medicine Institute, Monash University, Clayton, Victoria, Australia 2 The Brain and Mind Institute, The University of Western Ontario, Western Interdisciplinary Research Building, London, Ontario, Canada
*Correspondence: [email protected] (J.A. Bourne).
https://doi.org/10.1016/j.tins.2020.01.007 © 2020 Elsevier Ltd. All rights reserved.
1
Trends in Neurosciences
awareness (a ‘feeling’ or an intuition), but an experience that is not visual in nature (type II blindsight) [10]. Whether these are distinct categories or simply the opposite ends of a continuous distribution of awareness remains a matter of some debate (Box 1). In any case, the presence of some nonvisual awareness in type II blindsight has challenged theories surrounding the role of V1 in conscious awareness [11]. The nature of the experience reported by patients with type II blindsight remains controversial: is it simply a form of degraded vision or a nonvisual form of conscious awareness? [12,13]. In both types of blindsight, measurements of sympathetic activation such as pupil dilation and skin conductance have been observed during passive viewing of particular kinds of visual stimuli (such as fearful or happy faces) presented in the patients’ blind field [14], indicating shared unconscious visual processing. Other distinctions have been made, not in terms of the nature of the phenomenology in blindsight, but rather in terms of the spared visual abilities. Thus, some patients, whether they have type I or type II blindsight, can preshape and orient their hand in flight to match the dimensions and orientation of a target object when they reach out to grasp it, even though they are unable to report the object’s shape, dimensions, or orientation [15,16]. This residual ability has been termed ‘action blindsight’ [17]. Other patients exhibit covert shifts of attention and aspects of spatial orienting in the absence of any visual experience. This particular sensitivity to unseen visual stimuli has been described as ‘attention blindsight’ [17]. It could be argued that action blindsight requires attention blindsight; that is, patients must attend to the objects they are grasping. Some patients with cortical blindness can discriminate between different visual stimuli based on their form, hue, or motion, again, without any visual awareness of those properties. A special category of residual visual discrimination ability, in which patients with damage to V1 can discriminate between fearful, happy, and neutral facial expressions, without visual awareness, has been termed ‘affective blindsight’ [5,18]. Table 1 describes three of the most well-studied patients exhibiting blindsight and highlights the significant overlap between each of the abilities preserved. This brief review of some of the spared visual abilities that have been identified in blindsight almost certainly does not capture all the residual visual behaviour that is present in patients who have lost conscious vision after damage to V1. Moreover, the distinctions that have been made amongst different kinds of spared visually driven behaviour are unlikely to be hard and fast [19,20]. There Box 1. Modelling Consciousness to Different Types of Blindsight The degree of conscious access to visual stimuli presented within the scotoma of type I and type II blindsight patients remains a deeply rooted question in the psychophysical and philosophical literature. Blindsight represents visually driven behaviour in the absence of visual awareness. The presence of type II blindsight in some patients indeed suggests that V1 may not be required for conscious awareness. The two main models of consciousness that have been applied to blindsight cases to explain their paradoxical abilities are the workspace model and the phenomenological model. In the neuronal workspace model [80], consciousness is characterised by global processing throughout the entire brain by a series of modular circuits running in parallel. For a stimulus to reach conscious awareness, it must first be processed by unique workspace neurons that broadcast stimulus-relevant information to subsystems such as the visual sensory modality for motion stimuli. Workspace neurons are regulated in the volume and bandwidth of the information they process, which governs vital aspects of consciousness; its transient nature as seen in visual attention and its seamless nature (i.e., we perceive sensory information from different modalities as a single bound event rather than isolated events of visual, olfactory, and auditory experiences). It is believed that these workspace neurons are a part of the fronto-parietal attention network and are involved in selecting information in the occipital-temporal systems. In blindsight patients without the V1 subsystem, their altered workspace could result in changes to the transmission of information, resulting in perception somewhere between full consciousness and complete absence. In the phenomenological model [81], phenomenal consciousness is supported by repeated activity between two regions. For example, it is possible to have a phenomenal sense of motion when motion-selective cortex (area MT) and primary visual cortex (V1) enter a feedforward and feedback relationship. With the loss of this local recurrent activity in blindsight patients, area MT enters a different activation state between subcortical afferents such as the pulvinar or LGN and this could explain the blindsight spectrum of phenomenal awareness.
2
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
Glossary Blindsight: the ability to respond to visual stimuli presented into a patient’s blind field without the patient consciously perceiving them. This is often observed following damage to the primary visual cortex (V1). Extrastriate cortex: multiple visual association areas that extend beyond V1, each of which process specific elements of visual input but are strongly driven by their input from V1 in the uninjured brain. This includes V2 and V3, which have also been classified as ‘early’ visual areas. Lateral geniculate nucleus (LGN): a small, highly laminated nucleus of the thalamus parcellating visual signals from both eyes into three types of distinctive layers. Magno- and parvocellular layers comprise the main layers, being interleaved with koniocellular layers (K layers). The information, transmitted through the optic tract to the different layers of the LGN, is parcellated based on specific retinal ganglion cell input and thus visual properties. The parvocellular layers of the LGN receive information about colour and form, whereas the magnocellular layers receive information about motion and contrast sensitivity. The koniocellular layers receive a diverse mix of retinal inputs that tend to reflect the properties of inputs to adjacent parvo- or magnocellular layers. Middle temporal area (area MT/V5): a region of extrastriate cortex containing direction-selective neurons. Area MT participates in motion perception and is flanked by several satellite regions that collectively integrate motion signals to generate a global motion percept. These signals can then be relayed to higherorder visual areas to help guide visual behaviour. Area MT is also believed to be an important component in the development and maturation of the visual cortex, acting in some ways akin to V1. Pulvinar nuclei: the largest collection of thalamic nuclei (in primates) occupying the posterior pole of the thalamus. The nuclei of the pulvinar involved in vision are the inferior (PI) and lateral (PL) aspects, each of which have further subnuclei. They play a role in relaying retinal information to the cortex during development, handling cognitive processes such as spatial attention, and integrating cortical and subcortical visual signals. Saccade: a rapid, simultaneous movement of both eyes towards a particular region in the visual field.
Trends in Neurosciences
is the added difficulty of generalising findings from the observed behaviour in blindsight patients to related behaviour in the neurologically healthy individuals due to the genuine possibility of altered connectivity after brain damage. Indeed, since blindsight is not observed in all patients with V1 damage, it may be the case that blindsight is the result of modified neuronal connections rather than reflecting the inherent function of an intact brain. What is clear is that the pathways that have been implicated in blindsight are far less prominent than the geniculo-striate pathway in the neurologically intact visual system and the role of these pathways in mediating the range of residual visual abilities described above remains contentious. In the following section, we review the evidence for the putative pathways that have been proposed.
Candidate Substrates of Blindsight The pathways that have been proposed to support blindsight have included entirely subcortical routes from the eye to effectors, as well as pathways to extrastriate visual areas in the cerebral cortex that bypass the main geniculo-striate pathway. Also, it has been argued that some of these pathways, particularly those engaging the cerebral cortex, may have been rewired after damage to V1, mainly in cases where the damage occurred early in life. The presence of alternative pathways to the extrastriate cortex and their putative role in supporting blindsight have been extensively studied. Connectional and behavioural findings in non-human primates and imaging studies in patients with V1 damage have revealed a number of pathways (Figure 1A) that could support spared visual behaviour thought to be mediated by extrastriate areas [9,21,22]. Two pathways, one involving the koniocellular layers (K layers) of the lateral geniculate nucleus (LGN) and the other the pulvinar nuclei, have traditionally been identified as the most likely candidates [23–26]. Here, we summarise the evidence for each of these pathways from studies in non-human primates and consider to what extent these pathways can facilitate blindsight and what abilities are likely to be preserved. An anatomical feature the two pathways share is that both project to the visual middle temporal (MT) cortical area and its satellites, key cortical areas associated with the dorsal stream. Finally, we will consider other retinorecipient nuclei that have not been examined in recent years (Figure 2). If blindsight is indeed a modular phenomenon, we believe that the study of these areas could provide valuable insights into some aspects of the unconscious processing of visual information.
Saccades are believed to be controlled both cortically, by the frontal eye fields as well as areas in the posterior parietal cortex, and subcortically by the superior colliculus. Saccades are essential for changing fixation and attending to a stimulus. Scotoma: a localised region of blindness, or blind spot in the visual field. Specifically, it is an area of diminished/ absent visual acuity, which generally juxtaposes a region of normal vision. Although each mammalian eye has a scotoma due to the optic nerve head, the term is generally used in cases of altered vision. A scotoma typically arises from damage to the retina, V1, or the pathways from the retina to V1. Superior colliculus (SC): a laminated midbrain structure comprising (in primates) seven layers subdivided into three functional zones. The three superficial layers are retinorecipient; the two intermediate layers represent the integration of multiple sensory modalities, whereas the final two deep layers are motor-related, involved in the initiation of eye movements. Overall, the SC receives direct retinal information to guide saccades towards salient regions.
The Central Role of Area MT Specific retinorecipient subcortical pathways project directly to the middle temporal area (area MT/V5). This includes the LGN, via the K layers [21,27,28], the medial portion of the inferior pulvinar (PIm) [28,29], or indirectly via the superior colliculus (SC) to the remaining divisions of the inferior Table 1. List of Well-Studied Patients for Various Abilities Observed in Blindsight Patient
Nature and timing of injury
Action blindsight tested
Affective blindsight tested
Other abilities tested
T.N.
Adult-acquired (aged 52 years); bilateral V1 loss resulting from two consecutive strokes with a 36-day interval
Locomotion/navigation [83]
Emotional facial expression discrimination [84] at low spatial frequencies [3]
Visual mental imagery [86]
D.B.
Adult acquired; surgical ablation of right medial occipital lobe due to an arterious venus malformation
Pointing, spatial localization [2]
Emotional valence discrimination [14]
Detection and discrimination (orientation, motion direction, and form) [88]
G.Y.
Early-life acquired (aged ~7–8 years); traumatic brain injury damaged the left medial occipital lobe
Control of hand action [89]
Facial expression discrimination [18] with strengthened pathways between the pulvinar and amygdala [45]
Colour and motion discrimination, but not brightness [91]
Spatial orienting [90]
Emotional valence discrimination [14]
Amygdala response patterns to eye contact [85]
Categorical processing of visual stimuli [87]
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
3
Trends in Neurosciences
Trends in Neurosciences
Figure 1. Putative Subcortical Pathways Facilitating Blindsight. (A) Medial view schematic showing feedforward pathways travelling from the retina to extrastriate cortex in the PPC. Opaque pathways indicate neuronal degeneration as a result of V1 injury. (B,C) Proposed subcortical pathways for facilitating blindsight capacity following V1 injury in the developing brain (B) and the adult brain (C). Line thickness indicates the strength or relative density of the projection. Brain schematic in (A) generated using BioRender. Abbreviations: Amg, Amygdala; LGN, lateral geniculate nucleus; MT, middle temporal area; PI, inferior pulvinar; PIcl, caudolateral division of inferior pulvinar; PIcm, centromedial division of inferior pulvinar; PIm, medial division of inferior pulvinar; PIp, posterior division of inferior pulvinar; PPC, posterior parietal cortex; Pul, pulvinar; SC, superior colliculus.
pulvinar (PI) [30–32]. Although these pathways are well-mapped in the adult brain and convincingly reveal the central involvement of area MT, there remains controversy concerning which pathway plays the most prominent role in blindsight. Furthermore, the role of these pathways during development both in the intact brain and following V1 injury requires further investigation to elucidate their involvement in driving area MT activity. Finally, it is worth noting that it is likely that the projections from the K layers mediate spared visual abilities that are distinct from those mediated by projections from the pulvinar. Area MT in the developing brain shares many properties with V1 with respect to its cellular maturation patterns and dense myelination at birth, suggesting that it should be considered a 4
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
Trends in Neurosciences
Trends in Neurosciences
Figure 2. Retinorecipient Nuclei. Schematic showing all known retinal projections (in primates) grouped by region or functional system. Their broad functions are listed for each group. Subsequent feedforward and feedback projections are not shown. Abbreviations: AOS, Accessory optic system; LGN, lateral geniculate nucleus; M/D/LTN, medial/dorsal/lateral terminal nuclei; NOT, nucleus of the optic tract; OPN, olivary pretectal nucleus; PI, inferior pulvinar; PN, pretectal nuclei (including anterior, medial, and dorsal); PrG, pregeniculate nucleus; SC, superior colliculus; SCN, suprachiasmatic nucleus.
‘primary-like’ area [33,34]. Indeed, the strong presence of area MT within the developing brain makes it a prime candidate for facilitating visual input in the absence of V1 (see Box 2 for theories surrounding its early development). Despite the presence of robust V1 inputs to area MT in the adult brain [35], this connection is not fully established early in life [33,34], suggesting that the timing of a lesion to V1 could be a contributing factor to the degree of preserved residual vision. This conclusion has been supported by the fact that MT neurons continue to show vigorous activity after lesions of V1 in the developing brain [36–38]. Conversely, if the V1 injury occurs later in life, the typical responses of MT neurons are mostly attenuated [36] and instead their activity for motion [39] and contrast [40] sensitivity resembles the response patterns observed in V1 of neurologically intact individuals. Although these findings show that normal area MT activity relies on V1 input, they also illustrate how area MT can be reshaped during adulthood by putative subcortical pathways to mimic V1 activity at the expense of its normal functioning. Pulvinar Nuclei In recent years, a greater appreciation has emerged for the involvement of pulvinar nuclei in driving the development of area MT [29,41,42], specifically the PIm, and this thalamic nucleus is now a leading candidate for mediating the residual visual abilities in blindsight (Figure 1B). Pulvinar involvement in blindsight was traditionally thought to operate in conjunction with the collicular pathways, mediating visual attention by integrating eye movements with salient stimuli. PIm receives direct retinal input [28,29,43], expanding its possible role in mediating a range of
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
5
Trends in Neurosciences
Box 2. Hierarchical and Mosaic Patterns of Visual Development While the shared activity of the visual cortex enables our visual experience, it is comprised of multiple areas, each with their own unique connectivity and function. Understanding the mode of development can lead to inferences on which visual abilities would be likely to appear first. It was traditionally believed that the visual cortex develops in a hierarchical pattern, emanating from the early developed primary visual area (V1) to higher-order areas in a wave-like pattern. From V1, the wave bifurcated down two ‘streams’: a dorsal stream, handling spatial awareness and visually guided actions in the posterior parietal cortex, and a ventral stream, processing declarative information such as facial discrimination in the inferior temporal areas [82]. New lines of evidence have suggested that this proposed model of hierarchical development from the V1 hub may not progress in a strictly linear manner. Area MT, an extrastriate region involved in global motion processing, has been shown to develop and mature in parallel to V1 and other primary sensory modalities as evidenced by its dense myelination at birth and presence of mature pyramidal cells early in life [33,41]. Instead, it has been proposed that development may occur in a mosaic pattern, with large hubs such as V1 and area MT serving as developmental drivers of extrastriate cortex [34]. While the two streams are also present in the mosaic model of visual development, they develop asynchronously, which is likely due to the substantial driver input from area MT primarily to the dorsal-stream network. The afferent pathways providing visual input to area MT early in life are likely sourced from transient retino-pulvino projections that peak during development.
blindsight abilities (Figure 1). Specifically, it explains how area MT could receive instructive subcortical input during development, thereby strengthening dorsal-stream activity to visual stimuli before V1 input to MT is fully established. This has been supported by observations that the pulvinar is necessary for maintaining area MT activation by motion stimuli [44]. Furthermore, pulvinar afferents to MT outnumber V1 afferents early in life [29]. With the widespread connectivity of the pulvinar with both subcortical and cortical areas, it is ideally positioned to be involved in several abilities that can be preserved in blindsight patients. In an exclusively subcortical route, the interactions between the SC, pulvinar, and the amygdala have been considered essential for the mediation of affective blindsight in both humans [45] and monkeys [46]. Such cases involve individuals being able to correctly discriminate emotional stimuli presented within their blind field, for example, distinguishing between happy and fearful faces that are presented in a forced-choice manner [47]. These findings support the notion of an unconscious visual pathway that can extract affective features from facial expressions without input from higher-order areas of the ventral visual stream, involved in face and object recognition, in addition to the absence of V1 input [3–5]. Lateral Geniculate Nucleus Of interest, the interleaving K layers of the LGN [47] represent the V1-independent pathway to extrastriate cortex displaying sparse projections to area MT [27,48]. These K layers also receive visual information from the superficial visual layers of the SC [49]. This geniculo-extrastriate pathway has been widely studied, with substantial evidence demonstrating its involvement in adult blindsight patients (Figure 1C). Injuries to V1 trigger substantial retrograde degeneration of the optic radiations and, ultimately, the corresponding retinotopic region of the LGN [50,51]. The loss of LGN after V1 damage therefore appeared to favour the route from the SC to the pulvinar as the pathway responsible for blindsight abilities. Recently, however, the examination of LGN neurons in the putative K layers that survived V1 lesions at the site of degeneration revealed a viable pathway that remained visually responsive [52]. Although there was clearly degeneration of the main pathways from LGN and V1, projections from the K layers in LGN to area MT [53–55] are capable of contributing to blindsight abilities [56]. Although these tracts are not necessarily strengthened [57], they typically match those of healthy controls, suggesting their importance in maintaining the activation and function of area MT. There is also evidence to suggest that surviving LGN neurons can maintain connections with the extrastriate cortex, including V2, V3, and V4. In the absence of 6
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
Trends in Neurosciences
V1 input in macaques, neuronal responses that were motion-sensitive were found in V4, which could depend on input from K layers in LGN and/or MT [58]. Most of these findings have been explored in adult-acquired injuries of V1 and it remains unclear whether it is a viable pathway for blindsight cases sustained earlier in life. To put it in perspective, however, this pathway is much smaller than the one projecting from the pulvinar (PIm) to MT [59]. Superior Colliculus Although the SC has received less attention in the context of blindsight in recent years, it must not be overlooked. There is mounting evidence indicating its involvement in several cases of blindsight, or at the very least suggesting that its role cannot be categorically ruled out. Retinocollicular information can reach extrastriate cortex by relaying through both the PI [32,60] and the LGN [61], which then relay to MT and/or its satellites. These di-synaptic pathways may provide an extra level of information for extrastriate cortex interfacing sensorimotor input from the SC with the early-level detection of contrast and orientation from the LGN or pulvinar. In unilateral V1-lesioned macaque monkeys, reversible inactivation of the SC to pulvinar pathway resulted in the impairment of visually guided saccades to the blind field [62]. Furthermore, case studies demonstrated that an unconscious response could be induced through the presentation of achromatic stimuli in the blind field, with the response being attenuated if shortwavelength colour stimuli were used (such as purple) [63,64]. It was concluded that these cases likely had involvement of the SC-extrastriate cortex pathway, due to the lack of colour information the SC receives. In adults, the SC may also mediate perceptual organisation in the absence of V1, with one study revealing an increased sensitivity to structured stimuli rather than abstract stimuli presented in the blind field [65]. In addition, because the SC projects directly to premotor neurons in the brainstem, which mediate the control of visually guided saccades, it is highly capable of driving residual function, particularly eye movements, exclusively through subcortical routes. Rehabilitative investigations revealed that targeting multisensory neurons of the SC with audiovisual stimuli could improve visual responsiveness in the blind field across age groups [66]. By sharing connections with both the LGN and pulvinar, the SC may be a likely candidate for supporting blindsight for V1 damage that occurs throughout the lifespan; future studies are required to establish its contributions to blindsight following V1 damage early in life. Other Retinorecipient Nuclei Although the candidate pathways discussed above reflect the primary current viewpoints in the field, other retinorecipient nuclei could be involved (Figure 2). So far, we have discussed pathways that can reach higher-order cortices to mediate complex visually driven responses. In fact, the role of subcortical pathways in mediating reflexive responses to light and corrective postural functions in blindsight are largely uninvestigated. There is scant evidence linking the retinohypothalamic tract, the accessory optic system, or the pregeniculate nucleus of the thalamus (PrG) [67] to blindsight function. Notably, all these nuclei send projections to the SC, and some to the PI, which in turn can project to the extrastriate cortex. Of note, the primate PrG has been shown to modulate the activity of the suprachiasmatic nucleus (SCN) in entraining appropriate circadian rhythms [68], which raises the question of whether circadian-related changes exist in blindsight patients. There has been no investigation to our knowledge of possible disturbances in melatonin levels, sleep, or the response activities of SCN or PrG nuclei in patients with V1 lesions, but it is likely that such changes, if any, will be observed only in patients with bilateral V1 lesions who are completely cortically blind.
Blindsight as a Function of Age Early-Life V1 Injuries Monkeys and humans that receive damage to V1 earlier in life typically exhibit higher levels of residual vision [54,69–71], highlighting the role of the developing brain in the extent of blindsight Trends in Neurosciences, Month 2020, Vol. xx, No. xx
7
Trends in Neurosciences
acquisition. As a recent example, patient B.I., who presented with extensive bilateral V1 damage 2 weeks postnatally due to a rare metabolic disease, displayed exceptional residual visual abilities, many of which were quite conscious, and an increased PI-MT pathway in the left hemisphere [72]. Additionally, there was a recent finding in the marmoset monkey of a prominent early-life pulvino-MT connection [41], and while usually reduced by adulthood, it remains functional following V1 injury. Taken together, these findings highlight the role of the pulvinar in the preserved visual capacity observed in blindsight, but they do not categorically eliminate the contribution of geniculo-extrastriate pathways. The potential of the LGN to facilitate residual information during early life is diminished due to significant transneuronal degeneration of the retinogeniculostriate pathway occurring more rapidly in early life V1 lesions when compared with similar insults acquired during adulthood [50,51,73]. Indeed, repeated exposure to visual stimuli within the blind field of V1 lesioned patients can yield to the rescuing of residual function, presumably through geniculo-extrastriate projections [74]. In a recent functional magnetic resonance imaging study investigating the functional connections projecting to area MT, the LGN-MT pathway in the injured hemisphere exclusively determined whether patients with an adult-acquired V1 lesion would exhibit blindsight abilities, while the evidence for the role of the pulvinar-MT pathway was mixed [75]. Therefore, the putative roles of the LGN and pulvinar projections to area MT appear to be subject to the timing of the V1 lesion, each contributing at different stages of life. One study to date has challenged this hypothesis, finding that the activity of LGN neurons projecting to extrastriate cortex could be sufficiently viable for the preservation of visual function following V1 injury sustained at any age. This study highlights the fact that, despite degeneration in the LGN, the surviving neurons in this area maintain relatively normal properties and may be enough to support some visual information in blindsight patients [52]. There is strong interest in this conjecture, with new studies continuously adding more pieces to the puzzle. Given the rising interest and the emergence of new techniques, questions surrounding the relative involvement of the pulvinar and the LGN during visual cortical injury can potentially be resolved. V1 Injuries in the Mature Brain While the developing brain has a higher capacity to reorganise and restore function after injury when compared with the adult brain, maturation does not abolish the brain’s potential to recover visual function. In adult patients with unilateral V1 damage, one prominent hypothesis is that the processing of information by the intact hemisphere is sufficient for the maintenance of some blindsight capacities. The presence of blindsight in patients with bilateral V1 damage [55,72], however, conflicts with the notion that residual visual function is mediated by the unaffected hemisphere. These opposing findings may represent the fact that separate parallel pathways contribute to the plastic restoration of visual function. For example, if an intact V1 is present in the other hemisphere, it can assume a key role in stimulating extrastriate activity; otherwise subcortical pathways through either the LGN, PI, and SC can facilitate this instead. It has been suggested that one method of investigating the mechanisms of adult blindsight is to create a reversible ‘lesion’ in V1 via transcranial magnetic stimulation (TMS) [76]. In neurologically healthy individuals who received TMS, however, V1 was shown to be necessary for the unconscious (as well as conscious) perception of motion stimuli [77], with feedback from extrastriate regions such as area MT being required for both conscious [78] and unconscious awareness [79]. These findings suggest that the mechanisms of blindsight in patients who suffered V1 lesions as adults might be different from those supporting unconscious motion processing in neurologically intact individuals.
Concluding Remarks and Future Perspectives Advances in functional and connectivity imaging have revealed significant insights into the networks facilitating the preserved visual abilities seen in blindsight patients. As evidence from 8
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
Outstanding Questions What are the relative influences of the LGN, pulvinar, and SC in facilitating blindsight-like behaviours following early- or adult-life V1 injury? Are different residual abilities mediated by different spared visual pathways? To what extent are V1 pathways to extrastriate cortex hardwired to mediate conscious and unconscious visual awareness? What are the functions of the subcortical projections to extrastriate cortex? Can they permit the unconscious processing of visual stimuli such as motion and contrast in the neurologically intact population when V1 input is disrupted via TMS induction? Are specific residual functions such as ‘affective blindsight’ or ‘action blindsight’ mediated by different pathways, or can the visual system remodel existing and residual intact pathways to carry out all these functions? Does the extrastriate cortex respond to unilateral and bilateral V1 injuries similarly? Does the type of injury (e.g., stroke, blunt trauma) dictate the type or level of response? How do V1 lesions acquired during adulthood differ from those acquired in early life, when the brain is maturing? Which pathways are more likely to respond at different injury timings? Can we recapitulate the reorganisation of visual networks observed in early-life injuries in the adult network to facilitate greater preservation of visual function? Can we improve the blindsight capacities of patients over time using rehabilitative methods? Which methods are better suited at recovering the abilities to detect, localise, and discriminate stimuli in complex scenes?
Trends in Neurosciences
case studies and animal models accumulate, we are gaining a better understanding of the critical factors leading to spared visual abilities and how the impact of these factors can change over the lifespan. The future directions central to this field are outlined in the Outstanding Questions, which address the issues surrounding the contribution of different spared pathways to preserved visual abilities at a given time point in the lifespan. Addressing these questions will have significant implications not only for our understanding of the neural underpinnings of blindsight but also for our understanding of the constraints on visual plasticity following an injury at a network level. Once it is better understood how the visual system responds to primary visual cortical injury, one could employ rehabilitative strategies to enhance (or even direct) this process with the ultimate aim of improving residual visual capacity. Acknowledgements D.M.F. is supported by an Australian Government Research Training Program (RTP) Scholarship. J.A.B. is supported by a Senior Research Fellowship support (APP1077677) from the National Health and Medical Research Council (NHMRC). This work was supported by Project Grants from the National Health and Medical Research Council (APP1042893 & APP1138038). The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government. M.A.G.’s research is supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (RGPIN-2017-04-88) and a grant from the Canadian Institute for Advanced Research.
References 1.
2. 3. 4. 5.
6.
7.
8. 9.
10. 11. 12. 13. 14.
15.
16.
17.
Pöppel, E. et al. (1973) Residual visual function after brain wounds involving the central visual pathways in man. Nature 243, 295–296 Weiskrantz, L. et al. (1974) Visual capacity in the hemianopic field following a restricted occipital ablation. Brain 97, 709–728 Burra, N. et al. (2017) Affective blindsight relies on low spatial frequencies. Neuropsychologia 128, 44–49 Celeghin, A. et al. (2015) From affective blindsight to emotional consciousness. Conscious. Cogn. 36, 414–425 Striemer, C.L. et al. (2017) Affective blindsight in the absence of input from face processing regions in occipital-temporal cortex. Neuropsychologia 128, 50–57 Yoshida, M. et al. (2012) Residual attention guidance in blindsight monkeys watching complex natural scenes. Curr. Biol. 22, 1429–1434 Takaura, K. et al. (2011) Neural substrate of spatial memory in the superior colliculus after damage to the primary visual cortex. J. Neurosci. 31, 4233–4241 Danckert, J. and Goodale, M.A. (2000) Blindsight: a conscious route to unconscious vision. Curr. Biol. 10, R64–R67 Tamietto, M. and Morrone, M.C. (2016) Visual plasticity: blindsight bridges anatomy and function in the visual system. Curr. Biol. 26, R70–R73 Weiskrantz, L. (1997) Consciousness lost and found: a neuropsychological exploration, Oxford University Press Leopold, D.A. (2012) Primary visual cortex: awareness and blindsight. Annu. Rev. Neurosci. 35, 91–109 Mazzi, C. et al. (2016) Blind-sight vs. degraded-sight: different measures tell a different story. Front. Psychol. 7 Weiskrantz, L. (2009) Is blindsight just degraded normal vision? Exp. Brain Res. 192, 413–416 Tamietto, M. et al. (2009) Unseen facial and bodily expressions trigger fast emotional reactions. Proc. Natl. Acad. Sci. U. S. A. 106, 17661 Whitwell, R.L. et al. (2011) Grasping the non-conscious: preserved grip scaling to unseen objects for immediate but not delayed grasping following a unilateral lesion to primary visual cortex. Vis. Res. 51, 908–924 Prentiss, E.K. et al. (2018) Spontaneous in-flight accommodation of hand orientation to unseen grasp targets: a case of action blindsight. Cogn. Neuropsychol. 35, 343–351 Danckert, J. and Rossetti, Y. (2005) Blindsight in action: what can the different sub-types of blindsight tell us about the control of visually guided actions? Neurosci. Biobehav. Rev. 29, 1035–1046
18. De Gelder, B. et al. (1999) Non-conscious recognition of affect in the absence of striate cortex. Neuroreport 10, 3759–3763 19. Sahraie, A. et al. (1997) Pattern of neuronal activity associated with conscious and unconscious processing of visual signals. Proc. Natl. Acad. Sci. U. S. A. 94, 9406–9411 20. Weiskrantz, L. et al. (1995) Parameters affecting conscious versus unconscious visual discrimination with damage to the visual cortex (V1). Proc. Natl. Acad. Sci. U. S. A. 92, 6122–6126 21. Bridge, H. et al. (2008) Changes in connectivity after visual cortical brain damage underlie altered visual function. Brain 131, 1433–1444 22. Pavan, A. et al. (2011) Detection of first- and second-order coherent motion in blindsight. Exp. Brain Res. 214, 261–271 23. Cowey, A. (2010) Visual system: how does blindsight arise? Curr. Biol. 20, R702–R704 24. Yoshida, M. (2013) Neural mechanism of blindsight. Brain Nerve 65, 671–677 25. Schmid, M.C. and Maier, A. (2015) To see or not to see thalamo-cortical networks during blindsight and perceptual suppression. Prog. Neurobiol. 126, 36–48 26. Kaas, J. and Baldwin, M. (2019) The evolution of the pulvinar complex in primates and its role in the dorsal and ventral streams of cortical processing. Vision 4, 3 27. Sincich, L.C. et al. (2004) Bypassing V1: a direct geniculate input to area MT. Nat. Neurosci. 7, 1123–1128 28. Warner, C.E. et al. (2010) Retinal afferents synapse with relay cells targeting the middle temporal area in the pulvinar and lateral geniculate nuclei. Front. Neuroanat. 4, 8 29. Kwan, W.C. et al. (2018) Unravelling the subcortical and retinal circuitry of the primate inferior pulvinar. J. Comp. Neurol. 527, 558–576 30. Berman, R.A. and Wurtz, R.H. (2010) Functional identification of a pulvinar path from superior colliculus to cortical area MT. J. Neurosci. 30, 6342–6354 31. Berman, R.A. and Wurtz, R.H. (2008) Exploring the pulvinar path to visual cortex. Prog. Brain Res. 171, 467–473 32. Stepniewska, I. et al. (2000) Projections of the superior colliculus to subdivisions of the inferior pulvinar in New World and Old World monkeys. Vis. Neurosci. 17, 529–549 33. Bourne, J.A. and Rosa, M.G.P. (2006) Hierarchical development of the primate visual cortex, as revealed by neurofilament immunoreactivity: early maturation of the middle temporal area (MT). Cereb. Cortex 16, 405–414 34. Mundinano, I.C. et al. (2015) Mapping the mosaic sequence of primate visual cortical development. Front. Neuroanat. 9, 1–17
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
9
Trends in Neurosciences
35. Nassi, J.J. et al. (2006) The parvocellular LGN provides a robust disynaptic input to the visual motion area MT. Neuron 50, 319–327 36. Girard, P. et al. (1992) Response selectivity of neurons in area MT of the macaque monkey during reversible inactivation of area V1. J. Neurophysiol. 67, 1437–1446 37. Rosa, M.G.P. et al. (2000) Visual responses of neurons in the middle temporal area of New World monkeys after lesions of striate cortex. J. Neurosci. 20, 5552 38. Yu, H.H. et al. (2013) Visually evoked responses in extrastriate area MT after lesions of striate cortex in early life. J. Neurosci. 33, 12479–12489 39. Ajina, S. et al. (2015) Motion area V5/MT+ response to global motion in the absence of V1 resembles early visual cortex. Brain 138, 164–178 40. Ajina, S. et al. (2015) Abnormal contrast responses in the extrastriate cortex of blindsight patients. J. Neurosci. 35, 8201–8213 41. Warner, C.E. et al. (2012) The early maturation of visual cortical area MT is dependent on input from the retinorecipient medial portion of the inferior pulvinar. J. Neurosci. 32, 17073–17085 42. Mundinano, I-C. et al. (2018) Transient visual pathway critical for normal development of primate grasping behavior. Proc. Natl. Acad. Sci. U. S. A. 115, 1364–1369 43. Cowey, A. et al. (1994) Retinal ganglion cells labelled from the pulvinar nucleus in macaque monkeys. Neuroscience 61, 691–705 44. Barleben, M. et al. (2015) Neural correlates of visual motion processing without awareness in patients with striate cortex and pulvinar lesions. Hum. Brain Mapp. 36, 1585–1594 45. Tamietto, M. et al. (2012) Subcortical connections to human amygdala and changes following destruction of the visual cortex. Curr. Biol. 22, 1449–1455 46. Rafal, R.D. et al. (2015) Connectivity between the superior colliculus and the amygdala in humans and macaque monkeys: virtual dissection with probabilistic DTI tractography. J. Neurophysiol. 114, 1947–1962 47. Gerbella, M. et al. (2017) Pathways for smiling, disgust and fear recognition in blindsight patients. Neuropsychologia 128, 6–13 48. Hendry, S.H.C. and Clay Reid, R. (2000) The koniocellular pathway in primate vision. Annu. Rev. Neurosci. 23, 127–153 49. Zeater, N. et al. (2018) Projections of three subcortical visual centers to marmoset lateral geniculate nucleus. J. Comp. Neurol. 527, 535–545 50. Hendrickson, A. et al. (2015) Retrograde transneuronal degeneration in the retina and lateral geniculate nucleus of the V1lesioned marmoset monkey. Brain Struct. Funct. 220, 351–360 51. Atapour, N. et al. (2017) Neuronal degeneration in the dorsal lateral geniculate nucleus following lesions of primary visual cortex: comparison of young adult and geriatric marmoset monkeys. Brain Struct. Funct. 222, 3283–3293 52. Yu, H-H. et al. (2018) Robust visual responses and normal retinotopy in primate lateral geniculate nucleus following longterm lesions of striate cortex. J. Neurosci. 38, 3955–3970 53. Bridge, H. et al. (2010) Visual activation of extra-striate cortex in the absence of V1 activation. Neuropsychologia 48, 4148–4154 54. Ajina, S. et al. (2015) Human blindsight is mediated by an intact geniculo-extrastriate pathway. Elife 4, e08935 55. Ajina, S. and Bridge, H. (2019) Subcortical pathways to extrastriate visual cortex underlie residual vision following bilateral damage to V1. Neuropsychologia 128, 140–149 56. Schmid, M. et al. (2010) Blindsight depends on the lateral geniculate nucleus. Nature 466, 373–377 57. Bridge, H. et al. (2018) Intact extrastriate visual network without primary visual cortex in a rhesus macaque with naturally occurring blindsight. bioRxiv Published online October 18, 2018. https://doi.org/10.1101/447482 58. Schmid, M.C. et al. (2013) Motion-sensitive responses in visual area V4 in the absence of primary visual cortex. J. Neurosci. 33, 18740–18745 59. Mundinano, I-C. et al. (2019) Retinotopic specializations of cortical and thalamic inputs to area MT. Proc. Natl. Acad. Sci. U. S. A. 116, 201909799 60. Baldwin, M.K.L. et al. (2013) Projections of the superior colliculus to the pulvinar in prosimian galagos (Otolemur garnettii) and
10
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
61.
62.
63. 64.
65.
66.
67.
68.
69.
70.
71.
72.
73.
74.
75.
76.
77.
78.
79.
80.
81. 82. 83. 84.
85.
VGLUT2 staining of the visual pulvinar. J. Comp. Neurol. 521, 1664–1682 Harting, J.K. et al. (1991) Projection of the mammalian superior colliculus upon the dorsal lateral geniculate nucleus: organization of tectogeniculate pathways in nineteen species. J. Comp. Neurol. 304, 275–306 Kinoshita, M. et al. (2019) Dissecting the circuit for blindsight to reveal the critical role of pulvinar and superior colliculus. Nat. Commun. 10, 135 Tamietto, M. et al. (2010) Collicular vision guides nonconscious behavior. J. Cogn. Neurosci. 22, 888–902 Leh, S.E. et al. (2010) Blindsight mediated by an S-cone-independent collicular pathway: an fMRI study in hemispherectomized subjects. J. Cogn. Neurosci. 22, 670–682 Georgy, L. et al. (2016) The superior colliculus is sensitive to gestalt-like stimulus configuration in hemispherectomy patients. Cortex 81, 151–161 Tinelli, F. et al. (2015) Audio-visual stimulation improves visual search abilities in hemianopia due to childhood acquired brain lesions. Multisens. Res. 28, 153–171 Cowey, A. et al. (2001) The retinal projection to the pregeniculate nucleus in normal and destriate monkeys. Eur. J. Neurosci. 13, 279–290 Lima, R.R. et al. (2012) Retinal projections and neurochemical characterization of the pregeniculate nucleus of the common marmoset (Callithrix jacchus). J. Chem. Neuroanat. 44, 34–44 Gross, C.G. et al. (2004) Visually guided behavior after V1 lesions in young and adult monkeys and its relation to blindsight in humans. Prog. Brain Res. 144, 279–294 Moore, T. et al. (1996) Greater residual vision in monkeys after striate cortex damage in infancy. J. Neurophysiol. 76, 3928–3933 Werth, R. (2006) Visual functions without the occipital lobe or after cerebral hemispherectomy in infancy. Eur. J. Neurosci. 24, 2932–2944 Mundinano, I-C. et al. (2017) More than blindsight: case report of a child with extraordinary visual capacity following perinatal bilateral occipital lobe injury. Neuropsychologia 128, 178–186 Cowey, A. et al. (2011) Transneuronal retrograde degeneration of retinal ganglion cells and optic tract in hemianopic monkeys and humans. Brain 134, 2149–2157 Sahraie, A. et al. (2013) The continuum of detection and awareness of visual stimuli within the blindfield: from blindsight to the sighted-sight. Invest. Ophthalmol. Vis. Sci. 54, 3579–3585 Ajina, S. and Bridge, H. (2018) Blindsight relies on a functional connection between hMT+ and the lateral geniculate nucleus, not the pulvinar. PLoS Biol. 16, e2005769 Ro, T. and Rafal, R. (2006) Visual restoration in cortical blindness: insights from natural and TMS-induced blindsight. Neuropsychol. Rehabil. 16, 377–396 Hurme, M. et al. (2019) V1 activity during feedforward and early feedback processing is necessary for both conscious and unconscious motion perception. NeuroImage 185, 313–321 Hurme, M. et al. (2017) Early processing in primary visual cortex is necessary for conscious and unconscious vision while late processing is necessary only for conscious vision in neurologically healthy humans. NeuroImage 150, 230–238 Koivisto, M. et al. (2010) The role of early visual cortex (V1/V2) in conscious and unconscious visual perception. NeuroImage 51, 828–834 Dehaene, S. and Naccache, L. (2001) Towards a cognitive neuroscience of consciousness: basic evidence and a workspace framework. Cognition 79, 1–37 Block, N. (1995) On a confusion about a function of consciousness. Behav. Brain Sci. 18, 227–247 Goodale, M.A. and Milner, A.D. (1992) Separate visual pathways for perception and action. Trends Neurosci. 15, 20–25 de Gelder, B. et al. (2008) Intact navigation skills after bilateral loss of striate cortex. Curr. Biol. 18, R1128–R1129 Pegna, A.J. et al. (2005) Discriminating emotional faces without primary visual cortices involves the right amygdala. Nat. Neurosci. 8, 24–25 Burra, N. et al. (2013) Amygdala activation for eye contact despite complete cortical blindness. J. Neurosci. 33, 10483
Trends in Neurosciences
86. de Gelder, B. et al. (2015) Visual imagery influences brain responses to visual stimulation in bilateral cortical blindness. Cortex 72, 15–26 87. Van den Stock, J. et al. (2014) Neural correlates of body and face perception following bilateral destruction of the primary visual cortices. Front. Behav. Neurosci. 8 88. Trevethan, C.T. et al. (2007) Form discrimination in a case of blindsight. Neuropsychologia 45, 2092–2103
89. Jackson, S.R. (1999) Pathological perceptual completion in hemianopia extends to the control of reach-to-grasp movements. Neuroreport 10, 2461–2466 90. Kentridge, R.W. et al. (1999) Attention without awareness in blindsight. Proc. R. Soc. B Biol. Sci. 266, 1805–1811 91. Morland, A.B. et al. (1999) Visual perception of motion, luminance and colour in a human hemianope. Brain 122, 1183–1198
Trends in Neurosciences, Month 2020, Vol. xx, No. xx
11