Biology subjects

Kekunnaya, R.

Publications and source records attributed to Kekunnaya, R..

10 recordsLinked to original sources

bioRxiv2026

Early Vision Shapes Recurrent Processing in the Human Visual Cortex

Recurrent processing involves feedforward, feedback and lateral connections and is thought to allow efficient visual processing. Anatomical and behavioral studies in humans have suggested that feedback connections mature later in development than feedforward connections and thus were proposed to depend to a larger degree on experience. In order to isolate feedforward from feedback activity and to investigate the role of early visual experience, we assessed seven individuals with reversed congenital cataracts and nine sighted controls using an "occlusion paradigm" with 7T magnetic resonance imaging (Smith & Muckli, 2010): Grayscale images of scenes were presented with the lower right quadrant covered by a white rectangle. We examined whether information about category (beaches, buildings, highways) and individual scenes could be extracted from early visual region vertices (V1 - V3) associated with the occluded quadrant of the visual field, in the absence of bottom-up visual input. This was achieved by decoding individual category or scene context utilizing a linear support vector machine. In addition, bidirectional information flow was assessed using connective field modeling. While both groups showed successful decoding of scene and category from vertices receiving bottom-up visual input, the accuracy was higher in normally sighted individuals than in individuals with reversed congenital cataracts. When bottom-up input was removed, decoding of categories remained successful in both groups, but decoding of individual scenes was only possible in normally sighted control individuals. Connective field modeling results indicated a less precise alignment of feedforward and feedback processing during visual stimulation in individuals with reversed congenital cataracts. These findings suggest that early visual experience is crucial for the refinement of feedback activity which in turn is crucial for well-tuned feedforward processing.

neuroscience↗

bioRxiv2025

Individuals born with congenital cataracts exhibit both persisting impairment and considerable recovery of white matter microstructure after sight restoration

IntroductionIndividuals born with dense bilateral cataracts, for whom sight was restored later in life (congenital cataract reversal individuals), provide a unique opportunity to explore the impact of early (visual) experience on the development of the human brain. MethodsUsing diffusion MRI we assessed white matter microstructure in a sample of 20 congenital cataract reversal individuals using along-the-tract analysis of major visual white matter tracts and non-visual control tracts. We additionally recruited three control groups: 8 permanently congenitally blind individuals, 11 individuals with reversed later-onset cataracts (developmental cataract reversal individuals), and 24 age- and sex-matched typically sighted controls. ResultsDiffusion tensor metrics exhibited significant group differences which were specific to visual tracts. Compared to normally sighted controls, congenitally blind and congenital cataract reversal individuals both showed impaired white matter integrity. However, differences were much more spatially extensive for permanently congenitally blind individuals, and a direct comparison revealed relatively higher tract integrity for congenital cataract reversal individuals, suggesting a high degree of recovery following sight restoration. DiscussionThe present pattern of results is compatible with the idea of both a sensitive period for white matter development and significant white matter plasticity later in life. We propose that group differences are largely driven by differences in myelination. Thus, the considerable recovery in congenital cataract reversal individuals would suggest that life-long myelin plasticity may remain higher than neuronal structural plasticity.

neuroscience↗

bioRxiv2025

A Sensitive Period for the Development of Temporally Coherent Visual Cortical Processing in Humans: Evidence from Sight Recovery Following Congenital Cataracts

Proper timing is essential for effective neural processing. Yet, how early postnatal vision shapes the temporal stability of human visual cortical processing remains unknown. Here, using electroencephalography, we examined cortical timing properties in individuals who were born pattern vision blind due to congenital cataracts, but surgically recovered sight. While sight-recovery individuals exhibited an attenuated cortical oscillatory phase coherence (i.e., higher temporal variability) during visual processing, their oscillatory strength was unimpaired. Moreover, phase coherence information, but not activation strength, allowed the classification of sight-recovery from control individuals. Finally, exchanging phase information between sight-recovery and control individuals indicated oscillatory timing impairments as the source of group differences in higher-order visual cortical processing. Neural timing impairments were specific for reversed congenital blindness, that is, were not observed in individuals with reversed developmental (late-onset) cataracts. These results suggest that the development of intricately temporally orchestrated visual cortical processing in humans requires early visual experience. Significance StatementNeural circuit functioning requires an efficient temporal orchestration. The present work investigated how the temporal stability of visual cortical dynamics depends on adequate experience. In rare individuals who were born with pattern vision blindness but later recovered sight, a marked increase in the temporal variability of oscillatory brain activity during visual processing was observed while oscillatory strength was surprisingly unimpaired. Therefore, the emergence of precisely timed visual processing in the human brain seems to crucially depend on early visual experience. We speculate that impaired timing of neural processing, cascading throughout the visual cortical hierarchy, might be a major source of the incomplete visual recovery in individuals with treated congenital blindness.

neuroscience↗

bioRxiv2024

Visual and auditory object representations in ventral visual cortex after restoring sight in humans

Visual category-selective representations in human ventral occipital temporal cortex (VOTC) seem to emerge early in infancy. Surprisingly, the VOTC of congenitally blind humans features category-selectivity for auditory and haptic objects. Yet it has been unknown whether VOTC would show category-selective visual responses if sight were restored in congenitally blind humans. Assuming competition for synaptic space during development, cross-modal activation of VOTC as a consequence of congenital blindness might interfere with visual processing in sight-recovery individuals. To test this hypothesis, we investigated adults who had suffered a transient phase of congenital blindness due to bilateral dense cataracts before their sight was restored by cataract-removal surgery. In a functional magnetic resonance imaging (fMRI) study, participants watched movies of faces, scenes, body parts and other objects in the visual condition, while in the auditory condition they listened to the corresponding sounds. The most prominent group difference was the reduced face-selectivity in individuals with reversed congenital cataracts compared to age- and sex-matched normally-sighted individuals. In addition, a double dissociation was found: only sight-recovery individuals demonstrated significant decoding accuracy of visual categories based on auditory category representations in VOTC, while only normally-sighted individuals VOTC decoded auditory categories based on visual category representations. The present results uncovered the neural mechanisms of previously observed face processing impairments in individuals with reversed congenital blindness. We suggest that lower face-selectivity in the sight recovery group might arise from selective deficits in the cortical representation of the central visual field in lower-tier visual areas. Additionally, we speculate that in higher-order visual areas cross-modal activity might facilitate - rather than interfere - with visual functional recovery after congenital blindness.

neuroscience↗

bioRxiv2024

Altered visual cortex excitatory/inhibitory ratio following transient congenital visual deprivation in humans

Non-human animal models have indicated that the ratio of excitation to inhibition (E/I) in neural circuits is experience dependent and changes across development. Here, we assessed 3T Magnetic Resonance Spectroscopy (MRS) and electroencephalography (EEG) markers of cortical E/I ratio in ten individuals who had been treated for dense bilateral congenital cataracts, after an average of 12 years of blindness, to test for dependence of the E/I ratio in humans on early visual experience. First, participants underwent MRS scanning at rest with their eyes opened and eyes closed, to obtain visual cortex Gamma-Aminobutyric Acid (GABA+) concentration, Glutamate/Glutamine (Glx) concentration and the concentration ratio of Glx/GABA+, as measures of inhibition, excitation, and E/I ratio respectively. Subsequently, EEG was recorded to assess aperiodic activity (1-20 Hz) as a neurophysiological measure of the cortical E/I ratio, during rest with eyes open and eyes closed, and during flickering stimulation. Across conditions, congenital cataract-reversal individuals demonstrated a significantly lower visual cortex Glx/GABA+ ratio, and a higher intercept and steeper aperiodic slope at occipital electrodes, compared to age-matched sighted controls. In the congenital cataract-reversal group, a lower Glx/GABA+ ratio was associated with better visual acuity, and Glx concentration correlated positively with the aperiodic intercept in the conditions with visual input. We speculate that these findings result from an increased E/I ratio of the visual cortex as a consequence of congenital blindness, which might require commensurately increased inhibition in order to balance the additional excitation from restored visual input. The lower E/I ratio in congenital cataract-reversal individuals would thus be a consequence of homeostatic plasticity.

neuroscience↗

bioRxiv2023

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 during 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 0-30 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 had experienced transient congenital blindness.

neuroscience↗

bioRxiv2022

Detailed investigation on the role of lipid metabolizing enzymes in the pathogenesis of retinopathy of prematurity among preterm infants.

PurposeExtremely preterm infants are at risk of developing retinopathy of prematurity (ROP), characterized by an initial insufficient vascular network development in the retina (due to hyperoxia) that progress to neovascularization and neuroinflammation (hypoxic phase) ultimately leading to partial or total vision loss. Lipid metabolism has been shown to be a significant pathway that is involved in the regulation of angiogenesis, inflammation, and apoptosis in oxygen induced retinopathy mouse model, however, it is not explored in human ROP patients. The present study aimed to explore the association of lipid metabolizing, angiogenic and apoptotic genes with altered lipid metabolites in the ROP patients with different severity. MethodsThe blood, vitreous humor (VH), and fibrovascular membrane (FVM) samples were collected from premature infants diagnosed with ROP and controls. Gene expression of lipid metabolizing enzymes, angiogenesis, and apoptotic genes were performed using semi-quantitative PCR in blood. Lipid metabolites were identified and quantified by LC-MS in VH and were correlated with gene expression. The expression of key lipid metabolizing enzymes in severe stages of ROP was assessed by measuring their expression in FVM by immunohistochemistry. ResultsGenes coding for the lipid metabolizing enzymes such as CYP1B1, CYP2C8, COX2, and ALOX15 were upregulated while EPHX2 responsible for the conversion of epoxide fatty acids into diol fatty acids was significantly downregulated in ROP cases. The increase in the metabolic intermediates generated from the lipid metabolism pathway further confirmed the role of these enzymes in ROP. except for EPHX2 which did not show any change in its activity. The glial cells in the FVM of ROP infants too showed a lack of EPHX2 expression. A significantly higher expression of genes involved in angiogenesis (VEGF165/189, NOTCH1, and APH1B) and apoptosis (CASP3/8) correlated with altered activity of lipid metabolizing enzymes (based on metabolites levels) among ROP cases. ConclusionsLipid metabolism may play a significant role in ROP development and progression. EPHX2 activity is a key step in the metabolic pathway of arachidonic acid that mediates and regulates inflammation and vascular pathology in preterm infants.

genomics↗

bioRxiv2021

Typical resting state activity of the brain requires visual input during an early sensitive period

Sensory deprivation, following a total loss of one sensory modality e.g. vision, has been demonstrated to result in intra- and cross-modal plasticity. It is yet not known to which extent intra- and cross-modal plasticity as a consequence of blindness reverse if sight is restored. Here, we used functional magnetic resonance imaging to acquire blood oxygen level dependent (BOLD) resting state activity during an eyes open and an eyes closed state in congenital cataract-reversal individuals, developmental cataract-reversal individuals, congenitally permanently blind individuals and sighted controls. The amplitude of low frequency fluctuations (ALFF) of the BOLD signal - a neural marker of spontaneous brain activity during rest - was analyzed. As has been shown before, in normally sighted controls we observed an increase in ALFF during rest with the eyes open compared to rest with eyes closed in visual association areas and in parietal cortex but a decrease in auditory and sensorimotor regions. In congenital cataract-reversal individuals, we found an increase of the amplitude of slow BOLD fluctuations in visual cortex during rest with eyes open compared to rest with eyes closed too but this increase was larger in amplitude than in normally sighted controls. At the same time, congenital cataract-reversal individuals lagged a similar increase in parietal regions and did not show the typical decrease of ALFF in auditory and sensorimotor cortex. Congenitally blind individuals displayed an overall higher amplitude in slow BOLD fluctuations in visual cortex compared to sighted individuals and compared to congenital cataract-reversal individuals in the eyes closed condition. Higher ALFF in visual cortex of congenital cataract-reversal individuals than in normally sighted controls during eyes open might indicate an altered excitatory-inhibitory balance of visual neural circuits. By contrast, the lower parietal increase and the missing downregulation in auditory and sensorimotor regions suggest a reduced influence of the visual system on multisensory and the remaining sensory systems after restoring sight in congenitally blind individuals. These results demonstrate a crucial dependence of multisensory neural networks on visual experience during a sensitive phase in human brain development.

neuroscience↗

bioRxiv2021

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 visual and multisensory processing. Here, the Size-Weight-Illusion was used to test whether visuo-haptic integration recovers after sight restoration. In Experiment 1, congenital (CC: 7 (3F), 8-35 years) and developmental cataract reversal individuals (DC: 9 (2F), 8-37 years), as well as congenitally blind (CB: 2 (1F), 33 and 44 years) and normally sighted individuals (SC: 10 (7F), 19-36 years) perceived larger objects as lighter than smaller objects of the same weight. In Experiment 2, CC (6 (1F), 17-44.7 years) and SC (7 (5F), 21-29 years) individuals performed identically when tested without haptic size cues. Together, this suggested that early visual experience is not necessary to perceive the Size-Weight-Illusion.

neuroscience↗

bioRxiv2019

Cross-modal temporal biases emerge during early sensitive periods

Human perception features stable biases, such as perceiving visual events as later than synchronous auditory events. The origin of such perceptual biases is unknown, they could be innate or shaped by sensory experience during a sensitive period. To investigate the role of sensory experience, we tested whether a congenital, transient loss of vision, caused by bilateral dense cataracts, has sustained effects on the ability to order events spatio-temporally within and across sensory modalities. Most strikingly, individuals with reversed congenital cataracts showed a bias towards perceiving visual stimuli as occurring earlier than auditory (Exp. 1) and tactile (Exp. 2) stimuli. In contrast, both normally sighted controls and individuals who could see at birth but developed cataracts during childhood reported the typical bias of perceiving vision as delayed compared to audition. Thus, we provide strong evidence that cross-modal temporal perceptual biases depend on sensory experience and emerge during an early sensitive period.

neuroscience↗