Phenotypic divergence in sleep and circadian cycles linked by affective state and environmental risk related to psychosis.

STUDY OBJECTIVES: Environmental cues influence circadian rhythm timing and neurochemicals involved in the regulation of affective behavior. How this interplay makes them a probable nonspecific risk factor for psychosis is unclear. We aimed to identify the relationship between environmental risk for psychosis and circadian timing phenotypes sampled from the general population. METHODS: Using an online survey, we devised a cumulative risk exposure score for each of the 1898 survey respondents based on 23 empirically verified transdiagnostic risks for psychosis, three dimensions of affect severity, psychotic-like experiences, and help-seeking behavior. Quantitative phenotyping of sleep and circadian rhythms was undertaken using at-home polysomnography, melatonin and cortisol profiles, and 3-week rest-activity behavior in individuals with a high-risk exposure load (top 15% of survey respondents, n = 22) and low-risk exposure load (bottom 15% of respondents, n = 22). RESULTS: Psychiatric symptoms were present in 100% of the high-load participants and 14% of the low-load participants. Compared to those with a low-load, high-load participants showed a later melatonin phase which was reflected by a greater degree of dispersion in circadian timing. Phase relationships between later circadian melatonin phase and later actigraphic sleep onsets were maintained and these were strongly correlated with self-reported sleep mid-points. No differences were identified from polysomnography during sleep between groups. CONCLUSION: Distinguishing circadian timing from other sleep phenotypes will allow adaptation for dosage of time-directed intervention, useful in stabilizing circadian timekeeping physiology and potentially reducing the multisystemic disruption in mental health disorders.

Do environmental risk factors for the development of psychosis distribute differently across dimensionally assessed psychotic experiences?

Psychotic experiences (PE) are associated with poorer functioning, higher distress and the onset of serious mental illness. Environmental exposures (e.g. childhood abuse) are associated with the development of PE. However, which specific exposures convey risk for each type or dimension of PE has rarely been explored. The Oxford Wellbeing Life and Sleep (OWLS) survey includes 22 environmental risk factors for psychosis and was designed to examine how environmental risks are associated with specific dimensions of PE. Multivariate logistic regression models were fit using these risk factors to predict six dimensions of PE (perceptual abnormalities, persecutory ideation, bizarre ideas, cognitive disorganisation, delusional mood and negative symptoms). Models were built using only 70% of the data, and then fit to the remaining data to assess their generalisability and quality. 1789 (27.2% men; mean age = 27.6; SD = 10.9) survey responses were analysed. The risk factors predictive of the most PE were anxiety, social withdrawal during childhood and trauma. Cannabis and depression predicted three dimensions with both predicting bizarre ideas and persecutory ideation. Psychological abuse and sleep quality each predicted two dimensions (persecutory ideation and delusional mood). Risk factors predicting one PE dimension were age (predicting cognitive disorganisation), physical abuse (bizarre ideas), bullying and gender (persecutory ideation); and circadian phase (delusional mood). These results lend support for a continuum of psychosis, suggesting environmental risks for psychotic disorders also increase the risk of assorted dimensions of PE. Furthermore, it advocates the use of dimensional approaches when examining environmental exposures for PE given that environmental risks distribute differently across dimensions.

Sleep-Wake Disturbance Related to Ocular Disease: A Systematic Review of Phase-Shifting Pharmaceutical Therapies.

PURPOSE: Light input, via the eyes, is essential for regulating circadian rhythms. Eye diseases can cause disruption of vital biological rhythms. Of totally blind people, 87% report sleep problems. There are no UK guidelines for visual disturbance-related circadian rhythm disruption. Our objective was to systematically review the literature to determine the effectiveness of pharmacological agents on the sleep quality of patients with sleep disturbance related to ocular disease. METHODS: We searched CENTRAL, MEDLINE, EMBASE, PsycINFO, and CINAHL alongside protocol registries and citation searches. We assessed the risk of bias using the Cochrane Risk of Bias Assessment Tool and assessed the strength of overall evidence using GRADE criteria. RESULTS: Four studies (n=116) met the inclusion criteria. Low-quality evidence showed that melatonin can cause entrainment (1 study), increases in total sleep time (all 3 studies), and reduction in sleep latency (1 study). Low-to-moderate quality evidence showed tasimelteon causes a significant improvement in entrainment, midpoint of sleep timing, lower-quartile of night-time sleep, and upper-quartile of daytime sleep. CONCLUSIONS: Results should be treated with caution as the melatonin studies had risks of bias due to inadequate reporting of randomization and masking procedures. The tasimelteon trial had a risk of reporting bias due to changing the outcomes after enrolling participants. Despite the paucity of trials, melatonin and tasimelteon may cause entrainment and improve subjective sleep measures with limited side effects. TRANSLATIONAL RELEVANCE: Given the relative cost melatonin may be a viable choice for treatment of circadian rhythm sleep disorders in the blind and warrants further research.

Impact of Diabetic Retinopathy on Sleep, Mood, and Quality of Life.

Purpose: Diabetic retinopathy (DR) is associated with retinal neuronal and vascular damage. DR has previously been shown to affect the photosensitive retinal ganglion cells (pRGCs). PRGCs are essential for the entrainment of circadian rhythms; thus, DR progression could lead to worsening sleep quality and mood. We investigate the relationship between increasing DR severity, and its impact on sleep quality and mood. Methods: A total of 430 participants with DR, and 303 healthy controls with no ocular disease or preexisting sleep disorders were recruited. DR severity was grouped as follows: 1, mild nonproliferative (NPDR); 2, moderate/severe NPDR; and 3, proliferative diabetic retinopathy (PDR). Sleep, mood, and quality of life were assessed using the Pittsburgh Sleep Quality Index (PSQI), quality of life (SF-36), and Hospital Anxiety and Depression Score (HADS) questionnaires. Data were analyzed by severity of DR, and correlated with sleep, QOL, and mood and compared to controls. Results: No significant difference between PSQI scores in the DR group or the control group was identified despite severity of DR. Mean anxiety and depression scores were within the normal range for both groups. Despite a lower general health and physical function, the DR group had lower anxiety scores than controls. Conclusions: These data show that even in severe DR, sleep quality is similar to controls. However, this could be explained by the majority of individuals in this study having good visual acuities in the better eye with a residual population of pRGCs remaining unaffected by DR.

Chromatic Perceptual Learning but No Category Effects without Linguistic Input.

Perceptual learning involves an improvement in perceptual judgment with practice, which is often specific to stimulus or task factors. Perceptual learning has been shown on a range of visual tasks but very little research has explored chromatic perceptual learning. Here, we use two low level perceptual threshold tasks and a supra-threshold target detection task to assess chromatic perceptual learning and category effects. Experiment 1 investigates whether chromatic thresholds reduce as a result of training and at what level of analysis learning effects occur. Experiment 2 explores the effect of category training on chromatic thresholds, whether training of this nature is category specific and whether it can induce categorical responding. Experiment 3 investigates the effect of category training on a higher level, lateralized target detection task, previously found to be sensitive to category effects. The findings indicate that performance on a perceptual threshold task improves following training but improvements do not transfer across retinal location or hue. Therefore, chromatic perceptual learning is category specific and can occur at relatively early stages of visual analysis. Additionally, category training does not induce category effects on a low level perceptual threshold task, as indicated by comparable discrimination thresholds at the newly learned hue boundary and adjacent test points. However, category training does induce emerging category effects on a supra-threshold target detection task. Whilst chromatic perceptual learning is possible, learnt category effects appear to be a product of left hemisphere processing, and may require the input of higher level linguistic coding processes in order to manifest.

Impact of cataract surgery on sleep in patients receiving either ultraviolet-blocking or blue-filtering intraocular lens implants.

PURPOSE: Although visual impairment is a well-recognized consequence of cataract development, little is known about the ability of the melanopsin-based photosensitive retinal ganglion cells (pRGCs) to regulate sleep-wake timing in the presence of cataract. In this study, we replaced a cataractous natural crystalline lens with two different types of artificial intraocular lenses, a UV-blocking lens or a blue-filtering lens. We investigated the level of sleep disturbance before cataract surgery and any change in sleep due to improved light transmission following surgery and compared this in both types of intraocular lens. METHODS: Quality of sleep in 961 patients undergoing cataract surgery was assessed by administering the validated self-reported Pittsburgh Sleep Quality Index (PSQI) questionnaire. The PSQI distinguishes good sleepers from poor sleepers by scoring seven different sleep components over the last month, which are combined to produce an overall score for sleep quality. Patients received either an ultraviolet-blocking (UVB) clear intraocular lens (IOL) or a blue-filtering (BF) IOL. Questionnaires were completed four times: 1 month preoperatively and again 1, 6 (UVB-IOL only), and 12 months postoperatively. RESULTS: Half of the patients reported poor sleep in the presence of cataract in both the UVB-IOL (mean PSQI = 6.35; SD = 3.82) and BF-IOL (mean PSQI = 6.39; SD = 4.04) groups. Cataract removal improved overall sleep quality significantly 1 month postoperatively in the UVB-IOL (mean PSQI = 5.89; SD = 3.71) and BF-IOL (mean PSQI = 6.08; SD = 3.88) groups. Sleep latency also improved for the UVB-IOL (preoperative mean = 1.16; SD = 1.003) and BF-IOL (preoperative mean = 1.17; SD = 1.03) groups at 1 month (UVB-IOL group mean = 1.01; SD = 0.923 and BF-IOL group mean = 1.00; SD = 0.95), which was sustained at 6 months for the UVB-IOL group (mean = 1.02; SD = 0.93) and 12 months for both the UVB-IOL and BF-IOL groups (6 months: UVB-IOL group mean = 0.96; SD = 0.92 and for the BF-IOL group mean = 0.99; SD = 0.96). CONCLUSIONS: Overall sleep quality and sleep latency improves after removal of cataract irrespective of the type of IOL implanted. These data show that implantation of BF-IOL does not have a negative impact on the sleep-wake cycle.

Early auditory processing in area V5/MT+ of the congenitally blind brain.

Previous imaging studies of congenital blindness have studied individuals with heterogeneous causes of blindness, which may influence the nature and extent of cross-modal plasticity. Here, we scanned a homogeneous group of blind people with bilateral congenital anophthalmia, a condition in which both eyes fail to develop, and, as a result, the visual pathway is not stimulated by either light or retinal waves. This model of congenital blindness presents an opportunity to investigate the effects of very early visual deafferentation on the functional organization of the brain. In anophthalmic animals, the occipital cortex receives direct subcortical auditory input. We hypothesized that this pattern of subcortical reorganization ought to result in a topographic mapping of auditory frequency information in the occipital cortex of anophthalmic people. Using functional MRI, we examined auditory-evoked activity to pure tones of high, medium, and low frequencies. Activity in the superior temporal cortex was significantly reduced in anophthalmic compared with sighted participants. In the occipital cortex, a region corresponding to the cytoarchitectural area V5/MT+ was activated in the anophthalmic participants but not in sighted controls. Whereas previous studies in the blind indicate that this cortical area is activated to auditory motion, our data show it is also active for trains of pure tone stimuli and in some anophthalmic participants shows a topographic mapping (tonotopy). Therefore, this region appears to be performing early sensory processing, possibly served by direct subcortical input from the pulvinar to V5/MT+.

Isoluminant coloured stimuli are undetectable in blindsight even when they move.

Moving stimuli are the most effective of all in eliciting blindsight. The detection of static luminance-matched coloured stimuli is negligible or even impossible in blindsight. However, moving coloured stimuli on an achromatic background have not been tested. We therefore tested two blindsighted hemianopes, one of them highly experienced and the other much less so, to determine whether they could perform what should be one of the simplest of all motion tasks: detecting when an array of coloured stimuli moves. On each trial, they were presented in the hemianopic field with an array of spots, all red or green or blue or achromatic, in a circular window and on a white surround. The spots moved coherently in the first or second of two short intervals. The subject had to indicate the interval in which the motion had occurred. The luminance of the spots was varied across different blocks of trials, but the background luminance remained the same throughout. For each colour, there was a ratio of luminance between the spots and the white surround at which performance was not significantly better than chance, although at other ratios, performance was good to excellent, with the exception of blue spots in one subject. We conclude that detecting global coherent motion in blindsight is impossible when it is based on chromatic contrast alone.

Modulation of cortical excitability can speed up blindsight but not improve it.

Blindsight has been widely investigated and its properties documented. One property still debated and contested is the puzzling absence of phenomenal visual percepts of visual stimuli that can be detected with perfect accuracy. We investigated the possibility that phenomenal visual percepts of exogenous visual stimuli in patient GY might be induced by using transcranial direct current stimulation. High contrast and low contrast stimuli were presented as a moving grating in his blind hemifield. When left area MT/V5 was anodally stimulated during the presentation of high-contrast gratings, he never reported a phenomenal percept of a moving grating but showed perfect blindsight performance. When applied along with low contrast gratings, for which accuracy was titrated to 60-70 %, performance did not improve but responses were significantly faster. Cathodal stimulation had no effect. Results are explained in the framework of GY's reorganized cortical connexions and oscillatory patterns known to be involved in awareness in GY. The apparent presence of phenomenal visual percepts in earlier studies is shown to be a semantic confusion about what he means when he says that he sees in his blind field.

Are hemianopic monkeys and a human hemianope aware of visual events in the blind field?

In three hemianopic monkeys and one normal monkey who subsequently became hemianopic and in one human hemianope we measured reaction times to touch the remembered position of a brief visual target presented in the normal hemifield or in the blind hemifield, or on the blank trials where no visual target occurred and the correct response was to touch a separate and permanently outlined part of the display. This is the same procedure as first used to demonstrate blindsight in these hemianopic monkeys. In the present experiment physically salient high-contrast (0.95) grating stimuli, which we have previously shown are easily detected and localized in the blind field, were used, and the monkeys' reaction times were also measured. With rare exceptions the monkeys indicated that the visual targets in the blind field were blanks, but their otherwise identical motor responses to targets and blanks had significantly different latencies, which were longer for real targets than for blanks. The results indicate that when the monkeys detect that the stimulus has occurred but do not perceive it as a light, or are just guessing, reaction times are longer. Even when the target in the blind field was moving, it was categorized as a blank. In the human hemianope both high- and low-contrast stimuli were used, and the subject had to indicate whether he had been 'aware' or 'unaware' of the target, after making the reaching response. The latencies when he was correct and aware were significantly shorter than when he was unaware and 'just guessing'. However, he was also significantly faster to respond correctly to the blind-field target when he was unaware and correct than when he was unaware and incorrect, a difference reflected in his percentage correct scores even when totally unaware. Collectively, the results support the notion that the hemianopic monkeys, like the human hemianope, know that something has happened in the blind field as long as the stimuli are physically salient even though the stimuli are categorized as blanks, presumably because, like the human hemianope, there was no phenomenal visual percept.

Language networks in anophthalmia: maintained hierarchy of processing in 'visual' cortex.

Imaging studies in blind subjects have consistently shown that sensory and cognitive tasks evoke activity in the occipital cortex, which is normally visual. The precise areas involved and degree of activation are dependent upon the cause and age of onset of blindness. Here, we investigated the cortical language network at rest and during an auditory covert naming task in five bilaterally anophthalmic subjects, who have never received visual input. When listening to auditory definitions and covertly retrieving words, these subjects activated lateral occipital cortex bilaterally in addition to the language areas activated in sighted controls. This activity was significantly greater than that present in a control condition of listening to reversed speech. The lateral occipital cortex was also recruited into a left-lateralized resting-state network that usually comprises anterior and posterior language areas. Levels of activation to the auditory naming and reversed speech conditions did not differ in the calcarine (striate) cortex. This primary 'visual' cortex was not recruited to the left-lateralized resting-state network and showed high interhemispheric correlation of activity at rest, as is typically seen in unimodal cortical areas. In contrast, the interhemispheric correlation of resting activity in extrastriate areas was reduced in anophthalmia to the level of cortical areas that are heteromodal, such as the inferior frontal gyrus. Previous imaging studies in the congenitally blind show that primary visual cortex is activated in higher-order tasks, such as language and memory to a greater extent than during more basic sensory processing, resulting in a reversal of the normal hierarchy of functional organization across 'visual' areas. Our data do not support such a pattern of organization in anophthalmia. Instead, the patterns of activity during task and the functional connectivity at rest are consistent with the known hierarchy of processing in these areas normally seen for vision. The differences in cortical organization between bilateral anophthalmia and other forms of congenital blindness are considered to be due to the total absence of stimulation in 'visual' cortex by light or retinal activity in the former condition, and suggests development of subcortical auditory input to the geniculo-striate pathway.

Detection of first- and second-order coherent motion in blindsight.

Blindsight patients can detect fast moving stimuli presented within their blind field even when they deny any phenomenal visual experience. Although mounting evidence suggests the presence of different mechanisms and separate neural substrates underlying the processing of first-order (luminance-defined) and second-order (contrast-defined) motion, the perception of second-order motion in blindsight has scarcely been explored. In the present study, we investigated whether two blindsighted patients (GY and MS) can detect a variety of first- and second-order moving stimuli, and by using repetitive transcranial magnetic stimulation (rTMS), we assessed the role of V5/MT(+) and V3(+) in coherent motion processing. The hemianopes and four control subjects performed a two-interval forced-choice task in which they judged whether a pattern of coherently moving first-order or second-order textured squares moved in the first or second interval. They were not asked to report the direction of motion because neither of them could do so better than expected by chance. The results showed that MS, who has extensive destruction of the ventral cortical visual pathway as well as his V1 lesion, could not process second-order motion at all, whereas GY could perform second-order tasks but only at high-contrast modulation. This may have introduced first-order components in second-order moving stimuli and provided artifactual cues to motion. Moreover, rTMS delivered over area V5/MT(+) impaired detection of both first- and second-order motion in undamaged control subjects, whereas rTMS over V3(+) did not impair their performance in any of the stimuli employed. On the other hand, rTMS over V3(+) did impair GY's detection of first-order motion and high-contrast second-order moving textured squares that are likely to contain artifactual luminance cues. rTMS over V5/MT(+) impaired first-order motion detection in MS. Overall, the results suggest that neither of the blindsight patients can detect artifact-free second-order motion.

Transneuronal retrograde degeneration of retinal ganglion cells and optic tract in hemianopic monkeys and humans.

Transneuronal retrograde degeneration of retinal ganglion cells after removal of primary visual cortex (area V1) is well established by quantitative neurohistological analysis of the ganglion cell layer in monkeys, but remains controversial in human patients. Therefore, we first histologically examined retinal degeneration in sectioned archived retinae of 26 macaque monkeys with unilateral V1 ablation and post-surgical survival times ranging from 3 months to 14.3 years. In addition, the cross-sectional area of the optic tract was measured in archived coronal histological sections of the brain of every hemianopic monkey and in sections from 10 control monkeys with non-visual bilateral cortical lesions. The ratios of nasal and temporal retinal ganglion cell counts in the contralesional eye and ipsi/contralateral optic tract areas were calculated and compared. They show that the decline was initially more pronounced for the optic tract, slackened after 3 years post-lesion and was steeper for the ganglion cells thereafter. Nevertheless, both measures were highly correlated. Second, we calculated ratios from structural magnetic resonance images to see whether the optic tracts of four human hemianopes would show similar evidence of transneuronal degeneration of their ipsilesional optic tract. The results were consistent with extensive and time-dependent degeneration of the retinal ganglion cell layer. The measures of the optic tracts provide evidence for comparable transneuronal retinal ganglion cell degeneration in both primate species and show that structural magnetic resonance image can both reveal and assess it.

Visual activation of extra-striate cortex in the absence of V1 activation.

When the primary visual cortex (V1) is damaged, there are a number of alternative pathways that can carry visual information from the eyes to extrastriate visual areas. Damage to the visual cortex from trauma or infarct is often unilateral, extensive and includes gray matter and white matter tracts, which can disrupt other routes to residual visual function. We report an unusual young patient, SBR, who has bilateral damage to the gray matter of V1, sparing the adjacent white matter and surrounding visual areas. Using functional magnetic resonance imaging (fMRI), we show that area MT+/V5 is activated bilaterally to visual stimulation, while no significant activity could be measured in V1. Additionally, the white matter tracts between the lateral geniculate nucleus (LGN) and V1 appear to show some degeneration, while the tracts between LGN and MT+/V5 do not differ from controls. Furthermore, the bilateral nature of the damage suggests that residual visual capacity does not result from strengthened interhemispheric connections. The very specific lesion in SBR suggests that the ipsilateral connection between LGN and MT+/V5 may be important for residual visual function in the presence of damage to V1.

Reduced chromatic discrimination in children with autism spectrum disorders.

Atypical perception in Autism Spectrum Disorders (ASD) is well documented (Dakin & Frith, 2005). However, relatively little is known about colour perception in ASD. Less accurate performance on certain colour tasks has led some to argue that chromatic discrimination is reduced in ASD relative to typical development (Franklin, Sowden, Burley, Notman & Alder, 2008). The current investigation assessed chromatic discrimination in children with high-functioning autism (HFA) and typically developing (TD) children matched on age and non-verbal cognitive ability, using the Farnsworth-Munsell 100 hue test (Experiment 1) and a threshold discrimination task (Experiment 2). In Experiment 1, more errors on the chromatic discrimination task were made by the HFA than the TD group. Comparison with test norms revealed that performance for the HFA group was at a similar level to typically developing children around 3 years younger. In Experiment 2, chromatic thresholds were elevated for the HFA group relative to the TD group. For both experiments, reduced chromatic discrimination in ASD was due to a general reduction in chromatic sensitivity rather than a specific difficulty with either red-green or blue-yellow subsystems of colour vision. The absence of group differences on control tasks ruled out an explanation in terms of general task ability rather than chromatic sensitivity. Theories to account for the reduction in chromatic discrimination in HFA are discussed, and findings are related to cortical models of perceptual processing in ASD.

Edges, colour and awareness in blindsight.

It remains unclear what is being processed in blindsight in response to faces, colours, shapes, and patterns. This was investigated in two hemianopes with chromatic and achromatic stimuli with sharp or shallow luminance or chromatic contrast boundaries or temporal onsets. Performance was excellent only when stimuli had sharp spatial boundaries. When discrimination between isoluminant coloured Gaussians was good it declined to chance levels if stimulus onset was slow. The ability to discriminate between instantaneously presented colours in the hemianopic field depended on their luminance, indicating that wavelength discrimination totally independent of other stimulus qualities is absent. When presented with narrow-band colours the hemianopes detected a stimulus maximally effective for S-cones but invisible to M- and L-cones, indicating that blindsight is mediated not just by the mid-brain, which receives no S-cone input, or that the rods contribute to blindsight. The results show that only simple stimulus features are processed in blindsight.

The cortical basis of global motion detection in blindsight.

The importance of stimulus qualities such as orientation, motion and luminance in blindsight are well known but their cortical basis has been much less explored. We therefore studied the performance of two blindsighted hemianopic subjects (GY and MS), in a task in which the subject had to decide in which of two adjunctive intervals a pattern of global spots moved coherently, at a variety of speeds, in the hemianopic field. Their ability was compared with that of two control subjects with normal vision. Both hemianopes performed this simple discrimination well in their blind fields but their performance was impaired by repetitive transcranial magnetic stimulation (rTMS) applied over cortical area hV5/MT(+) although not, or only slightly, by stimulation over the region of V3 or the vertex. The result is a direct demonstration that area hV5/MT(+) is necessary for global motion detection in blindsight.

Pupillary responses to coloured and contourless displays in total cerebral achromatopsia.

In two patients with total acquired cortical colour blindness and in six control subjects we studied the binocular pupillary response to a variety of sharply defined coloured and grey displays that either had the same mean luminance as the background (isoluminant) or were of greater mean luminance. Despite their complete inability to identify or to discriminate between colours the patients, like the control subjects, showed a pupillary response to the structured coloured displays, even when they were masked by dynamic luminance changes. However, and unlike the control subjects, the patients showed no pupillary response when the coloured displays lacked sharp chromatic borders, as in Gabors or Gaussians. The results indicate that although chromatic processing still occurs in cortical colour blindness its function is solely to give rise to the detection of sharp boundaries which, in their case, can provide the perception of shape but not hue. In accordance with this, the patients could no longer describe the isoluminant borderless figures, which were often totally invisible to them despite their strong chromatic contrast with the background.

A blindsight conundrum: how to respond when there is no correct response.

Whereas research on blindsight customarily defines the correct responses to all visual stimuli presented to the cortically blind field, we here introduced a small number of unexpected 'no stimulus' trials in a localization task, to discover whether they would elicit the same responses as blind field targets. As no correct responses existed for the blank stimuli, our subjects, three hemianopic and one normal monkey, and one human hemianope who was aware of many blind-field targets, could either respond to these catch trials as to a target or refrain from responding. Visual stimuli were presented singly at four possible positions, two in the blind field of the hemianopes, and all subjects correctly localized the vast majority of targets in either hemifield. On blank trials, the monkeys, but not the human, often failed to respond, and when they did respond, all hemianopes almost invariably touched a target position in the blind field. Analysis of reaction times showed that necessarily false responses to blank stimuli took longer than responses to blind field targets. However, apart from one hemianopic monkey, incorrect target responses took as long as responses to blank stimuli. The human hemianope showed the same pattern of reaction times as the hemianopic monkeys unless he had to report on stimulus awareness and confidence. Then, his confidence reports and response times mirrored his awareness of the stimuli, but neither differed for correct versus false responses once these were separated for 'aware' versus 'unaware' trials. The hemianopic monkeys' response probability and reaction time data indicate that they, implicitly or explicitly, registered differences between target and blank stimuli and, in one case, even between false responses to blind-field and blank stimuli.