Distinct neural processes in grapheme-colour synaesthetes and semantic controls.

In synaesthetes, stimulation of one sensory pathway provokes a sensory experience (e.g. a colour concurrent) in a different sensory modality or sub-modality. Results of synaesthetic Stroop and priming tests indicate that the perception of a colour concurrent interferes with the processing of a veridical colour in synaesthetes. We here examined the congruency between a stimulus' colour and the colour concurrent both in grapheme-colour synaesthetes and in non-synaesthetes trained on grapheme-colour associations. Electrophysiological (electroencephalogram) and behavioural measurements were collected during a priming task that included grapheme-grapheme and grapheme-colour patch pairs. To investigate covert bidirectional synaesthesia, an additional inverted colour patch-grapheme condition was included. Both groups of participants showed longer reaction time and more negative-going N300 and N400 event-related potential (ERP) components on incongruent trials. Whereas ERP effects in the non-synaesthetes were largely confined to the late cognitive components N300, P300 and N400, the synaesthetes also showed congruency-dependent modulation of the early sensory component N170. Our results suggest that early cognitive processes distinguish cross-modal synaesthetic perceptions from acquired associations. The involvement of both early- and late-stage cognitive components in bidirectional synaesthesia possibly indicates similar feature-binding mechanisms during processing of opposite flow directions of information, namely grapheme-colour and colour-grapheme.

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.

Synaesthetic perception of colour and visual space in a blind subject: an fMRI case study.

In spatial sequence synaesthesia (SSS) ordinal stimuli are perceived as arranged in peripersonal space. Using fMRI, we examined the neural bases of SSS and colour synaesthesia for spoken words in a late-blind synaesthete, JF. He reported days of the week and months of the year as both coloured and spatially ordered in peripersonal space; parts of the days and festivities of the year were spatially ordered but uncoloured. Words that denote time-units and triggered no concurrents were used in a control condition. Both conditions inducing SSS activated the occipito-parietal, infero-frontal and insular cortex. The colour area hOC4v was engaged when the synaesthetic experience included colour. These results confirm the continued recruitment of visual colour cortex in this late-blind synaesthetes. Synaesthesia also involved activation in inferior frontal cortex, which may be related to spatial memory and detection, and in the insula, which might contribute to audiovisual integration related to the processing of inducers and concurrents.

Modality and variability of synesthetic experience.

In synesthesia, stimulation of one sensory or cognitive pathway leads to additional, involuntary experiences in a second sensory or cognitive pathway. We here review previous surveys on this neurologically based phenomenon and report the results of 63 synesthetes who completed our Internet and paper questionnaire on synesthesia. In addition to asking for personal data and information on the participant's synesthesia, the questionnaire focused on the components of the inducer that elicit or modulate synesthesia. Synesthesia was most often developmental (92%) and of the grapheme-color type (86%). Sixty-two percent of the participants perceived time-related words in a spatial configuration. Music-color synesthesia was common (41%), and synesthesia for natural and artificial sounds (33%) was higher than in previous estimates. Eighty-one percent of participants experienced more than one form of synesthesia. Multimodal synesthesia, in which inducer and concurrent belong to 2 different sensory modalities, occurred in 92% of the participants. Overall, auditory stimuli were most often reported as inducers, and visual concurrents were most common. Modulations of the synesthetic experiences such as changes of the concurrent color, expansion within the same or to a different sensory modality, or reduction of the number of inducers over time were reported by 17% of participants. This challenges the presumed consistency of synesthesia and the adequacy of the test-retest consistency score still most commonly used to assess the veracity of reported synesthesia. Implications of the high prevalence of cross-modal synesthesia and the variability of synesthesia are discussed.

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.

Functional rehabilitation of partial cortical blindness?

The current doctrine regards fields of partial cortical blindness as permanent once a temporally restricted window for spontaneous recovery has passed. Accordingly, neuropsychological rehabilitation mainly applies compensatory procedures that train patients to make better use of their sighted field. The more ambitious goal of functional recovery depends on the survival of pathways that continue to transmit retinal information from the blind field. Although wide-spread antero- and retrograde degeneration follows lesions that destroy or denervate the primary visual cortex and cause partial cortical blindness, several retinofugal pathways survive in cats, monkeys, and humans. In all three species, they subserve a variety of visual functions which develop and improve with practice. Post lesion plasticity is greater when the lesion occurs early in life, but changes in behavioural performance and brain responses have also been demonstrated in late lesion subjects. Although the extent of functional improvement is variable, and the most effective approaches still need to be established across cohorts, the evidence for perceptual learning in fields of cortical blindness indicates that the visual processes mediated by the surviving parts of the visual system can be harnessed to improve functional outcome.

ERP--correlates of response selection in a response conflict paradigm.

Neuroimaging and electrophysiological studies suggest that the anterior cingulate cortex (ACC) is involved in the cognitive control of response related action. A frontocentral negative ERP-component, the N2, which probably originates from the ACC, is usually enhanced in conflict-trials that demand an unexpected response. We here used stepped adjustment of response expectation in a response-cueing task, and measured how the N2 varied with global and local cue validity. Results showed that, irrespective of the current cue validity, response times, error rates, and the frontocentral components P2, N2 and P3 increased in unexpected trials. Nevertheless, a N2 was also seen in expected trials, and its latency correlated positively with reaction times, indicating that this potential does not express response conflict only. In line with roles suggested for the ACC, we here propose that the N2 is related to the process of response selection which influences subsequent processing stages reflected in the P3. Unexpected revisions of response programs enhance and delay the N2.

Blindsight, conscious vision, and the role of primary visual cortex.

What is the role the primary visual cortex (V1) in vision? Is it necessary for conscious sight, as indicated by the cortical blindness that results from V1 destruction? Is it even necessary for blindsight, the nonreflexive visual functions that can be evoked with stimuli presented to cortically blind fields? In the context of this controversial issue, I present evidence indicating that not only is blindsight possible, but that conscious vision may, to a varying degree, return to formerly blind fields with time and practice even in cases where functional neuroimaging reveals no V1 activation.

Stimulus cueing in blindsight.

When visual stimuli are presented in the cortically blind visual field of patients or monkeys with verified destruction of striate cortex, many subjects can voluntarily respond to them. In studies of this blindsight, the on- and/or offset of the visual stimulus is usually known to the subject, either because it is signaled in some way or because the subject can present the stimulus himself. To study the effect of stimulus uncertainty on the responses of four hemianopic monkeys and one human hemianope, we compared trials on which the subjects themselves could instantly trigger the stimulus with trials on which the same stimulus appeared 1-7 s after the start-light that normally served as the trigger was first touched. The latter manipulation diminished both the percentage of trials on which the subjects responded and the percentage correct when they did respond. As the start-light disappeared when touched in the first but not second condition, we interpret our results as indicating an influential role for attention in blindsight. Although keeping attention focused on the start-light and delaying the target impaired performance especially in the monkeys, localization was still significant in three and hardly affected in GY.

Task-irrelevant blindsight and the impact of invisible stimuli.

Despite their subjective invisibility, stimuli presented within regions of absolute cortical blindness can both guide forced-choice behavior when they are task-relevant and modulate responses to visible targets when they are task-irrelevant. We here tested three hemianopic patients to learn whether their performance in an attention-demanding rapid serial visual presentation task would be affected by task-irrelevant stimuli. Per trial, nine black letters and one white target letter appeared briefly at fixation; the white letter was to be named at the end of each trial. On 50% of trials, a task-irrelevant disk (-0.6 log contrast) was presented to the blind field; in separate blocks, the same or a very low negative contrast distractor was presented to the sighted field. Mean error rates were high and independent of distractor condition, although the high-contrast sighted-field disk impaired performance significantly in one participant. However, when trials with and without distractors were considered separately, performance was most impaired by the high-contrast disk in the blind field, whereas the same disk in the sighted field had no effect. As this disk was least visible in the blind and most visible in the sighted field, attentional suppression was inversely related to visibility. We suggest that visual awareness, or the processes that generate it and are compromised in the blind hemisphere, enhances or enables effective attentional suppression.

Cueless blindsight.

The term blindsight describes the non-reflexive visual functions that remain or recover in fields of absolute cortical blindness. As visual stimuli confined to such fields are subjectively invisible, they are customarily announced by visible or audible cues that inform the patients when to respond. The pervasive use of cueing has spawned the widely held assumption that sight and blindsight differ in that only blindsight requires cueing. To test this assumption, we measured detection of auditorily cued and un-cued stimuli in three hemianopic patients. Stimuli fell onto the photosensitive retina of the subjectively blind field, onto the objectively blind optic disc, and, in one patient, into a region where they evoked impoverished conscious sight. Regardless of whether cues were given, performance was highly significant in the latter region of poor sight, clearly above chance in the subjectively blind field, and random in the optic disc control condition. Moreover, cues enhanced detection only in the relatively blind field. Showing that blindsight performance persists when cues are omitted, the results imply that non-reflexive responses can be initiated in the absence of both stimulus awareness and perceptible cues.

Seeing 'where' through the ears: effects of learning-by-doing and long-term sensory deprivation on localization based on image-to-sound substitution.

BACKGROUND: Sensory substitution devices for the blind translate inaccessible visual information into a format that intact sensory pathways can process. We here tested image-to-sound conversion-based localization of visual stimuli (LEDs and objects) in 13 blindfolded participants. METHODS AND FINDINGS: Subjects were assigned to different roles as a function of two variables: visual deprivation (blindfolded continuously (Bc) for 24 hours per day for 21 days; blindfolded for the tests only (Bt)) and system use (system not used (Sn); system used for tests only (St); system used continuously for 21 days (Sc)). The effect of learning-by-doing was assessed by comparing the performance of eight subjects (BtSt) who only used the mobile substitution device for the tests, to that of three subjects who, in addition, practiced with it for four hours daily in their normal life (BtSc and BcSc); two subjects who did not use the device at all (BtSn and BcSn) allowed assessment of its use in the tasks we employed. The impact of long-term sensory deprivation was investigated by blindfolding three of those participants throughout the three week-long experiment (BcSn, BcSn/c, and BcSc); the other ten subjects were only blindfolded during the tests (BtSn, BtSc, and the eight BtSt subjects). Expectedly, the two subjects who never used the substitution device, while fast in finding the targets, had chance accuracy, whereas subjects who used the device were markedly slower, but showed much better accuracy which improved significantly across our four testing sessions. The three subjects who freely used the device daily as well as during tests were faster and more accurate than those who used it during tests only; however, long-term blindfolding did not notably influence performance. CONCLUSIONS: Together, the results demonstrate that the device allowed blindfolded subjects to increasingly know where something was by listening, and indicate that practice in naturalistic conditions effectively improved "visual" localization performance.

Image-to-sound conversion: experience-induced plasticity in auditory cortex of blindfolded adults.

The ability to adapt to environmental changes is based on the impressive capacity of the central nervous system for plasticity changes. A better understanding of the requirements of neuroplasticity will help to apprehend and predict the success of sensory prostheses. To investigate neuroplastic changes associated with (1) blindfolding and (2) the use of a mobile visual-auditory substitution system, five normally sighted adults underwent weekly measurements of neuromagnetic activity using a 122-channel whole head neuromagnetometer. The substitution device converted visual images into sound patterns. During measurements subjects listened to "geometric sounds" converted from images of geometric shapes, "natural sounds" representing photographs of everyday objects, as well as to original "environmental sounds". To assess the role of visual deprivation, three individuals were blindfolded throughout a 3-week testing period. To assess the effect of extended exposure to "visual sounds", three subjects-two blindfolded, one sighted-had free use of the substitution device. Neuromagnetic responses were restricted to the auditory cortex across all measurements. Activity at 100 ms after presentation of "natural sounds", but not other auditory stimuli, showed a significant enhancement over time only in blindfolded subjects using the substitution system, indicating that the combination of visual deprivation and practice facilitated intra-modal plasticity. The fact that changes occurred only in response to "natural sounds" probably reflects the increased behavioural relevance of this category evident only for blindfolded subjects using the substitution device.

Aware or unaware: assessment of cortical blindness in four men and a monkey.

In four patients and one monkey with unilateral visual field defects caused by retro-geniculate lesions we measured forced-choice localization of square-wave gratings as a function of contrast, and compared results from the patients' absolutely and relatively blind fields. In addition, the patients indicated verbally whether they were aware of the stimuli. We then switched to a signal detection task in which the subjects had to signal a stimulus as in the localization task, by touching it, no matter whether it appeared in the good or bad hemifield, and in addition to signal a blank trial by touching an outlined square now constantly present on the monitor, and designated the no-stimulus response area. In this way, we could compare a non-verbal procedure that we had previously used in hemianopic monkeys with a verbal one commonly used to assess visual awareness. The results showed a close correspondence between the two measures of awareness in the human subjects who signalled 'stimulus' only for targets that also evoked verbal aware responses, validating the non-verbal approach. The hemianopic monkey behaved more like a patient with an absolute rather than a relative defect, and perfectly localized high-contrast stimuli which she nevertheless treated as blanks in the vast majority of presentations in the signal detection task.

Chromatic priming in hemianopic visual fields.

In three monkeys made hemianopic by unilateral striate cortical ablation, in one normal monkey and in a human hemianope (GY), we measured reaction times to chromatic targets presented in the normal hemifield as a function of prior chromatic primes in the blind field. The first of our three tasks showed an unspecific priming effect in that the colour of the here unpredictive prime was irrelevant. However, when contingencies were changed in the second task so that the prime was usually valid, its colour did significantly influence reaction times in two of the hemianopic monkeys as well as in the human subject. Even when the primes lost their predictive value again in the third task, this chromatically specific effect persisted. We conclude that chromatic processing in the cortically blind field can be revealed with indirect approaches that measure residual processing by its influence on the reaction to stimuli in the normal field, and that the validity of the prime (whether it predicts the colour of the target) is especially important.