David Philip Crewther

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.

Inhibition of reaching and grasping actions as an element of cognitive control and executive function is a vital component of sensorimotor behaviour that is often impaired in patients who have lost sensorimotor function following a stroke. To date, there are few kinematic studies detailing the fine spatial and temporal upper limb movements associated with the millisecond temporal trajectory of correct and incorrect responses to visually driven Go/No-Go reaching and grasping tasks. Therefore, we aimed to refine the behavioural measurement of correct and incorrect inhibitory motor responses in a Go/No-Go task for future quantification and personalized rehabilitation in older populations and those with acquired motor disorders, such as stroke. An exploratory study mapping the kinematic profiles of hand movements in neurotypical participants utilizing such a task was conducted using high-speed biological motion capture cameras, revealing both within and between subject differences in a sample of healthy participants. These kinematic profiles and differences are discussed in the context of better assessment of sensorimotor function impairment in stroke survivors.

The mechanisms underlying visual anomalies observed in individuals with Autism Spectrum Disorder (ASD), presenting in the form of impaired global visual perception and enhanced local perception have long been debated. Researchers have sought to investigate the phenomenon of surround suppression, the inhibitory mechanism responsible for filtering visual noise in high contrast stimuli of increasing size. Mixed results have shown impaired gain control reduces surround suppression allowing for improved motion inspection in certain conditions, along with the possibility that receptive field size and population varies among the ASD population producing size-specific alteration in motion inspection. The present study aims to investigate whether the level of autistic traits predicts motion inspection time performance in a random dot kinetogram (RDK), a function of stimulus size and contrast. A total of 12 typically developing (TD) participants were screened and grouped by AQ score to indicate level of autistic traits (low, medium and high). Results revealed that the high AQ group’s motion inspection time significantly outperformed the mid AQ group for small and large central RDK of low contrast. This result suggests an interaction between temporal and spatial processing may have masked the effects of gain control and impaired surround suppression in higher contrast conditions, often seen in previous studies.

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.

This study examines the blood-oxygen level dependent (BOLD) activation of the brain associated with the four distinctive thinking styles associated with the four personality orientations of the Gountas Personality Orientations (GPO) survey: Emotion/Feeling-Action, Material/Pragmatic, Intuitive/Imaginative, and Thinking/Logical. The theoretical postulation is that each of the four personality orientations has a dominant (primary) thinking style and a shadow (secondary) thinking style/trait. The participants (N = 40) were initially surveyed to determine their dominant (primary) and secondary thinking styles. Based on participant responses, equal numbers of each dominant thinking style were selected for neuroimaging using a unique fMRI cognitive activation paradigm. The neuroimaging data support the general theoretical hypothesis of the existence of four different BOLD activation patterns, associated with each of the four thinking styles. The fMRI data analysis suggests that each thinking style may have its own cognitive activation system, involving the frontal ventromedial, posterior medial, parietal, motor, and orbitofrontal cortex. The data also suggest that there is a left hemisphere relationship for the Material/Pragmatic and Thinking/Logical styles and a right activation relationship for Emotional/Feeling and Intuitive/Imaginative styles. Additionally, the unique self-reflection paradigm demonstrated that perception of self or self-image, may be influenced by personality type; a finding of potentially far-reaching implications.

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). Thirty-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. Only SPQ-interpersonal and AQ-communication were significantly correlated with right hemisphere glutamate/GABA ratios and MMN latency ( p s<.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 (ß=86.6, p =.033), but only partially mediated the relationship between MMN latency and AQ-communication scores (ß=21.0, p =.093). These 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.

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.

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° 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.

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.