Sound suppresses earliest visual cortical processing after sight recovery in congenitally blind humans.

Neuroscientific research has consistently shown more extensive non-visual activity in the visual cortex of congenitally blind humans compared to sighted controls; a phenomenon known as crossmodal plasticity. Whether or not crossmodal activation of the visual cortex retracts if sight can be restored is still unknown. The present study, involving a rare group of sight-recovery individuals who were born pattern vision blind, employed visual event-related potentials to investigate persisting crossmodal modulation of the initial visual cortical processing stages. Here we report that the earliest, stimulus-driven retinotopic visual cortical activity (<100 ms) was suppressed in a spatially specific manner in sight-recovery individuals when concomitant sounds accompanied visual stimulation. In contrast, sounds did not modulate the earliest visual cortical response in two groups of typically sighted controls, nor in a third control group of sight-recovery individuals who had suffered a transient phase of later (rather than congenital) visual impairment. These results provide strong evidence for persisting crossmodal activity in the visual cortex after sight recovery following a period of congenital visual deprivation. Based on the time course of this modulation, we speculate on a role of exuberant crossmodal thalamic input which may arise during a sensitive phase of brain development.

Frequency of adapting events affects face aftereffects but not blur aftereffects.

The dynamics of visual adaptation remain poorly understood. Recent studies have found that the strength of adaptation aftereffects in the perception of numerosity depends more strongly on the number of adaptation events than on the duration of the adaptation. We investigated whether such effects can be observed for other visual attributes. We measured blur (perceived focus-sharp vs blurred adapt) and face (perceived race- Asian vs. White adapt) aftereffects by varying the number of adaptation events (4 or 16) and the duration of each adaptation event (0.25 s or 1 s). We found evidence for an effect of event number on face but not on blur adaptation, though the effect for faces was significant for only one of the two face adapt conditions (Asian). Our results suggest that different perceptual dimensions may vary in how adaptation effects accrue, potentially because of differences in factors such as the sites (early or late) of the sensitivity changes or nature of the stimulus. These differences may impact how and how rapidly the visual system can adjust to different visual properties.

Stimulus-evoked and resting-state alpha oscillations show a linked dependence on patterned visual experience for development.

Persistent visual impairments after congenital blindness due to dense bilateral cataracts have been attributed to altered visual cortex development within a sensitive period. Occipital alpha (8-14 Hz) oscillations were found to be reduced after congenital cataract reversal, while participants performed visual motion tasks. However, it has been unclear whether reduced alpha oscillations were task-specific, or linked to impaired visual behavior in cataract-reversed individuals. Here, we compared resting-state and stimulus-evoked alpha activity between individuals who had been treated for dense bilateral congenital cataracts (CC, n = 13, mean duration of blindness = 11.0 years) and age-matched, normally sighted individuals (SC, n = 13). We employed the visual impulse response function, adapted from VanRullen and MacDonald (2012), to test for the characteristic alpha response to visual white noise. Participants observed white noise stimuli changing in luminance with equal power at frequencies between 0 and 30 Hz. Compared to SC individuals, CC individuals demonstrated a reduced likelihood of exhibiting an evoked alpha response. Moreover, stimulus-evoked alpha power was reduced and correlated with a corresponding reduction of resting-state alpha power in the same CC individuals. Finally, CC individuals with an above-threshold evoked alpha peak had better visual acuity than CC individual without an evoked alpha peak. Since alpha oscillations have been linked to feedback communication, we suggest that the concurrent impairment in resting-state and stimulus-evoked alpha oscillations indicates an altered interaction of top-down and bottom-up processing in the visual hierarchy, which likely contributes to incomplete behavioral recovery in individuals who experienced transient congenital blindness.

Active vision in sight recovery individuals with a history of long-lasting congenital blindness.

What we see is intimately linked to how we actively and systematically explore the world through eye movements. However, it is unknown to what degree visual experience during early development is necessary for such systematic visual exploration to emerge. The present study investigated visual exploration behavior in ten human participants whose sight had been restored only in childhood or adulthood, after a period of congenital blindness due to dense bilateral congenital cataracts. Participants freely explored real-world images while their eye movements were recorded. Despite severe residual visual impairments and gaze instability (nystagmus), visual exploration patterns were preserved in individuals with reversed congenital cataract. Modelling analyses indicated that similar to healthy controls, visual exploration in individuals with reversed congenital cataract was based on the low-level (luminance contrast) and high-level (object components) visual content of the images. Moreover, participants used visual short-term memory representations for narrowing down the exploration space. More systematic visual exploration in individuals with reversed congenital cataract was associated with better object recognition, suggesting that active vision might be a driving force for visual system development and recovery. The present results argue against a sensitive period for the development of neural mechanisms associated with visual exploration.SIGNIFICANCE STATEMENTHumans explore the visual world with systematic patterns of eye movements, but it is unknown whether early visual experience is necessary for the acquisition of visual exploration. Here, we show that sight recovery individuals who had been born blind demonstrate highly systematic eye movements while exploring real-world images, despite visual impairments and pervasive gaze instability. In fact, their eye movement patterns were predicted by those of normally sighted controls and models calculating eye movements based on low- and high-level visual features, and they moreover took memory information into account. Since object recognition performance was associated with systematic visual exploration it was concluded that eye movements might be a driving factor for the development of the visual system.

Audiovisual spatial recalibration but not integration is shaped by early sensory experience.

To clarify the role of sensory experience during early development for adult multisensory learning capabilities, we probed audiovisual spatial processing in human individuals who had been born blind because of dense congenital cataracts (CCs) and who subsequently had received cataract removal surgery, some not before adolescence or adulthood. Their ability to integrate audio-visual input and to recalibrate multisensory spatial representations was compared to normally sighted control participants and individuals with a history of developmental (later onset) cataracts. Results in CC individuals revealed both normal multisensory integration in audiovisual trials (ventriloquism effect) and normal recalibration of unimodal auditory localization following audiovisual discrepant exposure (ventriloquism aftereffect) as observed in the control groups. In addition, only the CC group recalibrated unimodal visual localization after audiovisual exposure. Thus, in parallel to typical multisensory integration and learning, atypical crossmodal mechanisms coexisted in CC individuals, suggesting that multisensory recalibration capabilities are defined during a sensitive period in development.

Steady state evoked potentials indicate changes in nonlinear neural mechanisms of vision in sight recovery individuals.

Humans with a transient phase of congenital pattern vision deprivation have been observed to feature prevailing deficits, particularly in higher order visual functions. However, the neural correlates of these prevalent visual impairments remain unclear. To probe different visual processing stages, we measured steady state visual evoked potentials (SSVEPs) generated by luminance flicker stimuli at 6.1 Hz, with superimposed horizontal periodic motion at 2.1 Hz or 2.4 Hz. SSVEP responses at the fundamental and second harmonic of luminance flicker frequency, and at their intermodulation frequencies with motion information, were analyzed. Three groups were tested: (1) 15 individuals who had suffered a lack of pattern vision from birth due to the presence of bilateral total congenital cataracts (CC group), which were surgically removed between 4 months and 22 years of age, (2) 13 individuals with reversed developmental i.e., later developing cataracts (DC group), and (3) normally sighted control participants (SC group; n = 13) matched in age and sex to the CC individuals. SSVEPs at the second harmonic frequency (i.e., 12.2 Hz) and at the intermodulation frequencies (8.2 Hz, and 8.5 Hz) were attenuated in the CC group. In contrast, fundamental frequency responses (i.e., at 6.1 Hz) were not significantly altered in the CC group compared to the control groups (SC and DC groups). Based on previous evidence on the role of striate vs. extrastriate generators of fundamental vs. second harmonics of SSVEPs, these results provide evidence for a stronger experience dependence of extrastriate than striate cortical processing, and furthermore, suggest a sensitive period for the development of putative nonlinear neural mechanisms hypothesized to mediate visual feature binding.

The size-weight illusion is unimpaired in individuals with a history of congenital visual deprivation.

Visual deprivation in childhood can lead to lifelong impairments in multisensory processing. Here, the Size-Weight Illusion (SWI) was used to test whether visuo-haptic integration recovers after early visual deprivation. Normally sighted individuals perceive larger objects to be lighter than smaller objects of the same weight. In Experiment 1, individuals treated for dense bilateral congenital cataracts (who had no patterned visual experience at birth), individuals treated for developmental cataracts (who had patterned visual experience at birth, but were visually impaired), congenitally blind individuals and normally sighted individuals had to rate the weight of manually explored cubes that differed in size (Small, Medium, Large) across two possible weights (350 g, 700 g). In Experiment 2, individuals treated for dense bilateral congenital cataracts were compared to sighted individuals in a similar task using a string set-up, which removed haptic size cues. In both experiments, indistinguishable SWI effects were observed across all groups. These results provide evidence that early aberrant vision does not interfere with the development of the SWI, and suggest a recovery of the integration of size and weight cues provided by the visual and haptic modality.

An electrophysiological biomarker for the classification of cataract-reversal patients: A case-control study.

BACKGROUND: Untreated congenital blindness through cataracts leads to lasting visual brain system changes, including substantial alterations of extrastriate visual areas. Consequently, late-treated individuals (> 5 months of age) with dense congenital bilateral cataracts (CC) exhibit poorer visual function recovery compared to individuals with bilateral developmental cataracts (DC). Reliable methods to differentiate between patients with congenital and developmental cataracts are often lacking, impeding efficient rehabilitation management and introducing confounds in clinical and basic research on recovery prognosis and optimal timing of surgery. A persistent reduction of the P1 wave of visual event-related potentials (VERPs), associated with extrastriate visual cortical activity, has been reported in CC but not in DC individuals. Using two experiments, this study developed and validated P1-based biomarkers for diagnosing a history of congenital blindness in cataract-reversal individuals. METHODS: Congenital and developmental cataract-reversal individuals as well as typically sighted matched controls took part in a first experiment used for exploring an electrophysiological biomarker (N CC = 13, N DC = 13, N Control = 26). Circular stimuli containing gratings were presented in one of the visual field quadrants while visual event-related potentials (VERPs) were recorded. Two biomarkers were derived from the P1 wave of the VERP: (1) The mean of the normalized P1 amplitude at posterior electrodes, and (2) a classifier obtained from a linear support vector machine (SVM). A second experiment with partially new CC/DC individuals and their matched controls (N CC = 14, N DC = 15, N Control = 29) was consecutively used to validate the classification based on both biomarkers. Performance of the classifiers were evaluated using receiver operating characteristic (ROC) curve analyses. All cataract-reversal individuals were tested after at least one year of vision recovery. FINDINGS: The normalized P1 amplitude over posterior electrodes allowed a successful classification of the CC from the DC individuals and typically sighted controls (area under ROC curve, AUC = 0.803 and 0.929 for the normalized P1 amplitude and the SVM-based biomarker, respectively). The validation for both biomarkers in experiment 2 again resulted in a high classification success (AUC = 0.800 and 0.883, respectively for the normalized P1 amplitude and the SVM-based biomarker). In the most conservative scenario involving classification of CC from DC individuals in a group of only cataract-reversal individuals, excluding typically sighted controls, the SVM-based biomarker was found to be superior to the mean P1 amplitude based biomarker (AUC = 0.852 compared to 0.757 for the mean P1 based biomarker in validation). Minimum specificity obtained was 80% across all biomarkers. INTERPRETATION: A persistent reduction of the P1 wave provides a highly specific method for classifying cataract patients post-surgically as having suffered from bilateral congenital vs. bilateral developmental cataracts. We suggest that using the P1 based non-invasive electrophysiological biomarker will augment existing clinical classification criteria for individuals with a history of bilateral congenital cataracts, aiding clinical and basic research, recovery prognosis, and rehabilitation efforts. FUNDING: German Research Foundation (DFG) and the European Research Council (ERC).

Biological Action Identification Does Not Require Early Visual Input for Development.

Visual input during the first years of life is vital for the development of numerous visual functions. While normal development of global motion perception seems to require visual input during an early sensitive period, the detection of biological motion (BM) does not seem to do so. A more complex form of BM processing is the identification of human actions. Here, we tested whether identification rather than detection of BM is experience dependent. A group of human participants who had been treated for congenital cataracts (CC; of up to 18 years in duration, CC group) had to identify ten actions performed by human line figures. In addition, they performed a coherent motion (CM) detection task, which required identifying the direction of CM amid the movement of random dots. As controls, developmental cataract (DC) reversal individuals (DC group) who had undergone the same surgical treatment as CC group were included. Moreover, normally sighted controls were tested both with vision blurred to match the visual acuity (VA) of CC individuals [vision matched (VM) group] and with full sight [sighted control (SC) group]. The CC group identified biological actions with an extraordinary high accuracy (on average ∼85% correct) and was indistinguishable from the VM control group. By contrast, CM processing impairments of the CC group persisted even after controlling for VA. These results in the same individuals demonstrate an impressive resilience of BM processing to aberrant early visual experience and at the same time a sensitive period for the development of CM processing.

Sensory experience during early sensitive periods shapes cross-modal temporal biases.

Typical human perception features stable biases such as perceiving visual events as later than synchronous auditory events. The origin of such perceptual biases is unknown. To investigate the role of early sensory experience, we tested whether a congenital, transient loss of pattern vision, caused by bilateral dense cataracts, has sustained effects on audio-visual and tactile-visual temporal biases and resolution. Participants judged the temporal order of successively presented, spatially separated events within and across modalities. Individuals with reversed congenital cataracts showed a bias towards perceiving visual stimuli as occurring earlier than auditory (Expt. 1) and tactile (Expt. 2) stimuli. This finding stood in stark contrast to normally sighted controls and sight-recovery individuals who had developed cataracts later in childhood: both groups exhibited the typical bias of perceiving vision as delayed compared to audition. These findings provide strong evidence that cross-modal temporal biases depend on sensory experience during an early sensitive period.

Successful visually guided eye movements following sight restoration after congenital cataracts.

Sensitive periods have previously been identified for several human visual system functions. Yet, it is unknown to what degree the development of visually guided oculomotor control depends on early visual experience-for example, whether and to what degree humans whose sight was restored after a transient period of congenital visual deprivation are able to conduct visually guided eye movements. In the present study, we developed new calibration and analysis techniques for eye tracking data contaminated with pervasive nystagmus, which is typical for this population. We investigated visually guided eye movements in sight recovery individuals with long periods of visual pattern deprivation (3-36 years) following birth due to congenital, dense, total, bilateral cataracts. As controls we assessed (1) individuals with nystagmus due to causes other than cataracts, (2) individuals with developmental cataracts after cataract removal, and (3) individuals with normal vision. Congenital cataract reversal individuals were able to perform visually guided gaze shifts, even when their blindness had lasted for decades. The typical extensive nystagmus of this group distorted eye movement trajectories, but measures of latency and accuracy were as expected from their prevailing nystagmus-that is, not worse than in the nystagmus control group. To the best of our knowledge, the present quantitative study is the first to investigate the characteristics of oculomotor control in congenital cataract reversal individuals, and it indicates a remarkable effectiveness of visually guided eye movements despite long-lasting periods of visual deprivation.

Color vision in sight recovery individuals.

BACKGROUND: Color vision has been consistently shown to be unaffected in animals that are raised in dark or in color-deprived environments. However, there are only a few studies that directly addressed the effect of congenital visual deprivation in color perception in humans. OBJECTIVE: The goal of the current study was to assess the effect of congenital visual deprivation on color vision using a panel based color arrangement test. METHODS: We investigated the recovery of color vision using the Farnsworth D15 test in a group of individuals who had experienced visual deprivation since birth due to bilateral dense congenital cataracts before undergoing cataract-reversal surgery (Congenital cataract, CC, n = 12). In addition, we tested two groups of control participants: (1) individuals who had had non-dense congenital cataract or developed cataract later in their childhood (Developmental cataract, DC, n = 10), and (2) sighted controls with normal or corrected to normal vision (n = 14). Based on the methods proposed by Vingrys and King-Smith (1988), we derived the following metrics of color vision performance: (1) total error score, (2) confusion index, (3) confusion angle, and (4) selectivity index. RESULTS: All of the measured indices of color vision performance were unaltered by a period of congenital visual deprivation. CONCLUSIONS: Our results support the view that, development of visual functions such as color discrimination and color arrangement does not depend on typical visual experience during a sensitive phase in early childhood.

A Protracted Sensitive Period Regulates the Development of Cross-Modal Sound-Shape Associations in Humans.

Humans preferentially match arbitrary words containing higher- and lower-frequency phonemes to angular and smooth shapes, respectively. Here, we investigated the role of visual experience in the development of audiovisual and audiohaptic sound-shape associations (SSAs) using a unique set of five groups: individuals who had suffered a transient period of congenital blindness through congenital bilateral dense cataracts before undergoing cataract-reversal surgeries (CC group), individuals with a history of developmental cataracts (DC group), individuals with congenital permanent blindness (CB group), individuals with late permanent blindness (LB group), and controls with typical sight (TS group). Whereas the TS and LB groups showed highly robust SSAs, the CB, CC, and DC groups did not-in any of the modality combinations tested. These results provide evidence for a protracted sensitive period during which aberrant vision prevents SSA acquisition. Moreover, the finding of a systematic SSA in the LB group demonstrates that representations acquired during the sensitive period are resilient to loss despite dramatically changed experience.