Biology subjects

Crewther, D. P.

Publications and source records attributed to Crewther, D. P..

8 recordsLinked to original sources

bioRxiv2025

A theoretical mechanism for ocular emmetropization.

Currently, the human myopia epidemic is estimated to affect nearly 3 billion persons, yet experimental refractive error research is still hampered by the lack of a plausible theoretical mechanism explaining how the eye detects defocus and grows to minimise error (emmetropization). Applied lens defocus, either positive or negative, to animals including human, induces rapid changes in both refraction and axial length. Such changes have been linked to the rate of transfer of fluid from the vitreous chamber across the Retinal Pigment Epithelium (RPE). However, the theoretical basis of sensing the sign of defocus still eludes, as does the physiological operationalisation of this defocus signal. We propose that the signal for the sign of defocus is contained within the pattern of temporal modulation of light on the retina during the myriad saccadic eye movements performed every minute. This pattern is generated by a combination of the ocular point spread function for the defocused eye, narrow cone photoreceptor acceptance of light and the modification of photoreceptor directionality by the retinal shear that accompanies saccadic eye movements. Thus, under conditions of defocus, performing a saccade across a simple visual grating produces an out of focus dynamic stimulus pattern on the retina which is sawtooth-like, the profile being dependent on the sign of defocus. Positive lens defocus induces a fast-OFF/slow-ON sawtooth-like luminance modulation transfer function, while negative lens defocus results in a fast-ON/slow-OFF temporal pattern. Such patterns produce relative incremental or decremental changes in the trans-epithelial electrical potential and consequent changes in fluid absorption across the RPE. Thus, rearing with positive lens defocus is associated with an increase in trans-epithelial potential, increasing trans-epithelial absorption and decreasing vitreous chamber size, while rearing with a negative lens decreases the trans-epithelial electrical potential and decreases RPE fluid absorption, increasing eyeball size. In both cases, retinal images become more in-focus, and the refractive error tends to zero. The resultant is emmetropization, modifying eyeball size in response to applied defocus in a stable negative feedback fashion.

neuroscience↗

bioRxiv2021

Red backgrounds have different effects on electrophysiological responses to fearful faces in groups with low and high autistic tendency

Visual processing differences in the magnocellular pathway have been reported across the autistic spectrum. On the basis that the firing of primate Type IV magnocellular cells is suppressed by diffuse red backgrounds, several groups have used red backgrounds as a means to investigate magnocellular contributions to visual processing in humans. Here, we measured emotional identification accuracy, and compared the P100 and N170 responses from groups with low (n=21; AQ<11) and high (n=22; AQ>22) Autism Spectrum Quotient (AQ) scores, in response to low (LSF) and high (HSF) spatially filtered fearful and neutral face stimuli presented on red and green backgrounds. For the LSF stimuli, the low AQ group correctly identified fearful expressions more often when presented on a red compared to a green background. The low AQ group also showed red backgrounds reduced the effect of LSF fearful expressions on P100 amplitudes. In contrast, the high AQ group showed that background colour did not significantly alter P100 responses to LSF stimuli. Interestingly, red background reduced the effects of HSF stimuli for the high AQ group. The effects of background color on LSF and HSF facial emotion responses were not evident for the N170 component. Our findings suggest that presenting face stimuli on a red background alters both magnocellular and parvocellular contributions to the P100 waveform, and that these effects differ for groups with low and high autistic tendencies. In addition, a theoretical model for explaining the temporal differences in facial emotion processing for low and high AQ groups is proposed.

neuroscience↗

bioRxiv2021

Concurrent Multimodal Data Acquisition During Brain Scanning is within Reach

BackgroundPrevious brain-scanning research exploring the neural mechanisms underpinning visuomotor planning and control has mostly been done without simultaneous motion-tracking and eye-tracking. Employing concurrent methodologies would enhance understanding of the brain mechanisms underlying visuomotor integration of cognitive, visual, ocular, and motor aspects of reaching and grasping behaviours. Therefore, this work presents the methods and validation for a high-speed, multimodal and synchronized system to holistically examine neural processes that are involved in visually-guided movement. MethodsThe multimodal methods included high speed 3D motion tracking (Qualisys), 2D eye-tracking (SR Research), and magnetoencephalography (MEG; Elekta) that were synchronized to millisecond precision. Previous MRIs were taken to provide improved spatial localization. The methods section describes the system layout and acquisition parameters to achieve multimodal synchronization. Pilot results presented here are preliminary data from a larger study including 29 participants. Using a pincer grip, five people (3 male, 2 female, ages 30-32) reached for and grasped a translucent dowel 50 times, after it was pseudorandomly illuminated. The object illumination was the Go cue. Seven discrete time points (events) throughout the task were chosen for investigation of simultaneous brain, hand and eye activity associated with specific visual (Go cue), oculomotor (1st saccade after Go), motor (Reaction Time; RT, Maximum Velocity: MV, Maximum Grip Width; MGW) or cognitive (Ready, End) mechanisms. Time-frequency analyses were performed on the MEG data sourced from the left precentral gyrus to explore task-related changes time-locked to these chosen events. Pilot resultsBasic kinematic parameters including RT, MV, MGW, Movement Time, and Total Time were similar to previous, seminal research by Castiello, Paulignan and Jeannerod, (1991), using a similar task. Although no gaze instructions were given, eye-tracking results indicated volunteers mostly gazed at or near the target object when Ready (72%), and then hardly looked away throughout the rest of the task at the important events sampled here (92% - 98%). At the End event, when lifting the dowel, on average, participants gazed at or near the target object 100% of the time. Although saccades > 100 ms after Go, but prior to RT were made on average in about one fourth (M = 13, SD = 6) of trials, a mixed model (REML) indicated their latency in timing after the Go was significantly (F = 13.376, p = .001) associated with RT scores on those trials (AIC = 724, R m2 = 0.407, Rc2= 0.420). Neural activity relative to baseline in the beta band was desynchronized for the visually guided reach periods, beginning prior to Go, and remaining sustained until beyond End, after the grasp and lift were executed. ConclusionThis study presents the layout, acquisition parameters and validation for a multimodal, synchronized system designed to record data from the hand, eye and brain simultaneously, with millisecond precision during an ecologically-valid prehension task with physical, 3D objects. The pilot results align with previous research made with single or bimodal data recordings. This multimodal method enables full-brain modelling that can holistically map the precise location and timing of neural activity involved in the visual, oculomotor, motor and cognitive aspects of reach-to-grasp planning and control.

neuroscience↗

bioRxiv2021

Intranasal oxytocin modulates very early visual processing of emotional faces

Functional imaging and behavioural studies have shown that the neuropeptide oxytocin influences processing of emotional faces. However, it is not clear whether these effects reflect modulation at an early or late stage of affective processing. We investigated the effects of oxytocin administration on early and late visual evoked potentials (VEP) in response to faces with neutral, fearful and happy expressions. In addition, we measured multifocal VEP and its associated nonlinearities to ascertain whether any changes observed in electrophysiology were indicative of a generalised effect or of one tied strictly to emotional processing. In a randomized, double-blind, cross-over design, 27 healthy male participants self-administered a nasal spray of either oxytocin (24 IU) or placebo. At very early latencies (40-60ms), oxytocin reduced right-temporal responses to fearful faces (d = .51), and central responses to both fearful (d = .48) and neutral faces (d = .54). For left occipito-temporal electrode sites, oxytocin decreased P100 reactivity to fearful expressions (d = 0.72). Oxytocin also decreased the amplitudes of the vertex positive potential (140-180ms) and late positive potential (400-600ms), regardless of whether the faces had fearful, happy or neutral expressions. The mfVEP showed no signs of selective magno-or parvo-cellular peak modulation comparing OXT with placebo with either low or high contrast stimulation. These results suggest that at early stages of visual processing, nasal oxytocin modulates responses to facial emotions, whereas at later stages of visual processing, it appears to influence more general face processing mechanisms. In addition, the measurable effects of OXT appear to be not a result of generalized brain change, but systematically related to emotional processing.

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bioRxiv2019

Cortical excitation-inhibition ratio mediates the effect of pre-attentive auditory processing deficits on interpersonal difficulties

Several lines of evidence identify aberrant excitatory-inhibitory neural processes across autism and schizophrenia spectrum disorders, particularly within the psychosocial domain. Such neural processes include increased excitatory glutamate and reduced inhibitory GABA concentrations, which may affect auditory pre-attentive processing as indexed by the mismatch negativity (MMN); thus, an excitation-inhibition imbalance might lead to aberrant MMN, which might in turn drive the relationship between the MMN and psychosocial difficulties. This research has the potential to enhance the neurochemical understanding of the relationship between electrophysiology (MMN) and behavioural/clinical measures (psychosocial difficulties).\n\nThirty-eight adults (18 male, 18-40 years) completed the Schizotypal Personality Questionnaire (SPQ) and Autism-Spectrum Quotient (AQ). Glutamate and GABA concentrations in bilateral superior temporal cortex (STC) were quantified using proton magnetic resonance spectroscopy (1H-MRS) while auditory MMN to a duration deviant was measured with magnetoencephalography. Spearman correlations probed the relationships between STC glutamate/GABA ratios, MMN amplitude and latency, and AQ and SPQ dimensions. Mediation effects of glutamate/GABA ratios on the relationship between MMN and AQ-SPQ dimensions were probed using causal mediation analysis.\n\nOnly SPQ-interpersonal and AQ-communication were significantly correlated with right hemisphere glutamate/GABA ratios and MMN latency (ps<.05), which were themselves correlated (p=.038). Two mediation models were investigated, with right MMN latency as predictor and SPQ-interpersonal and AQ-communication as outcome variables. Right STC glutamate/GABA ratios significantly mediated the relationship between MMN latency and SPQ-interpersonal scores ({beta}=86.6, p=.033), but only partially mediated the relationship between MMN latency and AQ-communication scores ({beta}=21.0, p=.093).\n\nThese findings support the growing body of literature pointing toward an excitation-inhibition imbalance that is central to psychosocial functioning across multi-dimensional spectrum disorders, such as autism and schizophrenia, and provides neurochemical indicators of the processes that underlie psychosocial dysfunction.

neuroscience↗

bioRxiv2019

Metacontrast masking as a measure of change detection: Children with poor reading fluency show impaired change detection for both letters and shapes.

Developmental dyslexia, a specific learning difficulty in reading, manifests as effortful decoding of words and as such is commonly associated with reduced phonemic awareness. However, its underlying cause remains elusive, with magnocellular visual processing, temporal auditory processing, visual attentional deficits and cerebellar dysfunction all gaining some traction. More recent theories have concerned visual attention span, measuring the parallel attentive capacity of the sensory visual system. However the VA span task as implemented requires reports, both conscious recall and recognition of letters, that activate many cortical areas beyond sensory visual cortex. Change detection, in contrast, does not require the conscious recognition of items, but simply awareness that the stimulus has changed, or not, again testing visual attention in a parallel fashion, but avoiding the complications of higher order cognitive processes. Thus, we investigated change detection in 33 good and poor readers with ages of around 10 yr, using a gap paradigm. Groups of 4 letters or 4 shapes were presented for a fixed time (0.7 s), followed after a 0.25 s gap, by a second similar group, each item surrounded by an annular frame filled with dynamic random noise of variable contrast. Detection performance was manipulated by varying the contrast of these meta-contrast mask frames, yielding a threshold contrast of the frames at which participants could just detect change. In two separate experiments, letters and rectangular shapes were used as target items, in order to test whether previous findings of superior change detection in good compared with poor readers was a result of greater automaticity in letter recognition of the good readers. The results indicate that the good readers were able to detect change at higher levels of masking distraction for both the letter and shape targets, indicating that this difference is not specifically related to to the training of graphemic or lexical information but more likely reflects a difference in alerting or pre-recognition stages of visual processing. Together, the results provide further support of the notion that there is a low level attentional performance difference between dyslexic and normal reading children. Thus, the results further bring transient spatial attention directly into the spotlight as an ability critical for learning to read.

neuroscience↗

bioRxiv2019

Dyslexic children show altered temporal structure of the nonlinear VEP.

The neural basis of dyslexia remains unresolved, despite many theories relating dyslexia to dysfunction in visual magnocellular and auditory temporal processing, cerebellar dysfunction, attentional deficits, as well as excessive neural noise. Recent research identifies perceptual speed as a common factor, integrating several of these systems. Optimal perceptual speed invokes transient attention as a necessary component, and change detection in gap paradigm tasks is impaired in those with dyslexia. This research has also identified an overall better change detection for targets presented in the upper compared with lower visual fields. Despite the magnocellular visual pathway being implicated in the aetiology of dyslexia over 30 years ago, objective physiological measures have been lacking. Thus, we employed nonlinear visual evoked potential (VEP) techniques which generate second order kernel terms specific for magno and parvocellular processing as a means to assessing the physiological status of poor readers (PR, n=12) compared with good readers (GR, n=16) selected from children with a mean age of 10yr. The first and second order Wiener kernels using multifocal VEP were recorded from a 4{degrees} foveal stimulus patch as well as for upper and lower visual field peripheral arcs. Foveal responses showed little difference between GR and PR for low contrast stimulation, except for the second slice of the second order kernel where lower peak amplitudes were recorded for PR vs GR. At high contrast, there was a trend to smaller first order kernel amplitudes for short latency peaks of the PR vs GR. In addition, there were significant latency differences for the first negativity in the first two slices of the second order kernel. In terms of peripheral stimulation, lower visual field response amplitudes were larger compared with upper visual field responses, for both PR and GR. A trend to larger second/first order ratio for magnocellularly driven responses suggests the possibility of lesser neural efficiency in the periphery for the PR compared with the GR. Stronger lower field peripheral response may relate to better upper visual field change detection performance when target visibility is controlled through flicking masks. In conclusion, early cortical magnocellular processing at low contrast was normal in those with dyslexia, while cortical activity related to parvocellular afferents was reduced. In addition, the study demonstrated a physiological basis for upper versus lower visual field differences related to magnocellular function.

neuroscience↗

bioRxiv2019

Visual mapping on the brain - caveats for multifocal fMRI

While multifocal electroretinography has become a standard ophthalmological technique, its use in cortical neuroimaging has been lesser. Vanni et al. (2005) presented the first exploration of the multifocal visual mapping methodology with fMRI. This commentary confirms the utility of this method, but also presents empirical results which suggest caveats for the use of the technique. In the current study rapid multifocal fMRI was established using m-sequence pseudo-random binary stimuli applied to visual field mapping in six young adults with normal vision. Nine contiguous regions of visual field - two rings of 4 patches with a central patch, areas scaled for cortical magnification, were pseudo-randomly stimulated, with patterned or grey images. The decorrelation of stimulus patches allowed all 256 volumes to be used for the analysis of each of the nine stimulus areas. Strong localized activation was observed for each of the four peripheral regions with the location of the activation conforming to the expected visual field retinotopy. The inner regions, including the foveal patch, did not significantly activate. We propose, on the basis of a simple correlational model of simulated eye movements, that the loss of signal is due to gaze instability. Thus, while the rapid multifocal method can be successfully applied to fMRI, the results appear quite sensitive to eye movements, the effects of which may have been overlooked by smoothing evoked responses to achieve a retinotopic map.

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