A Theoretical Analysis of the Influence of Fixational Instability on the Development of Thalamocortical Connectivity

Under natural viewing conditions, the physiological inotability of visual fixation keeps the projection of the stimulus on the retina in constant motion. After eye opening, chronic exposure to a constantly moving retinal image might influence the experience-dependent refinement of cell response characteristics. The results of previous modeling studies have suggested a contribution of fixational instability in the Hebbian maturation of the receptive fields of V1 simple cells (Rucci, Edelman, & Wray, 2000; Rucci & Casile, 2004). This paper presents a mathematieal explanation of our previous computational results. Using quasi-linear models of LGN units and V1 simple cells, we derive analytical expressions for the second-order statistics of thalamocortical activity before and after eye opening. We show that in the presence of natural stimulation, fixational instability introduces a spatially uncorrelated signal in the retinal input, whieh strongly influences the structure of correlated activity in the model

Modeling the Possible Influences of Eye Movements on the Refinement of Cortical Direction Selectivity

The second-order statistics of neural activity was examined in a model of the cat LGN and V1 during free-viewing of natural images. In the model, the specific patterns of thalamocortical activity required for a Bebbian maturation of direction-selective cells in VI were found during the periods of visual fixation, when small eye movements occurred, but not when natural images were examined in the absence of fixational eye movements. In addition, simulations of stroboscopic reming that replicated the abnormal pattern of eye movements observed in kittens chronically exposed to stroboscopic illumination produced results consistent with the reported loss of direction selectivity and preservation of orientation selectivity. These results suggest the involvement of the oculomotor activity of visual fixation in the maturation of cortical direction selectivity

Exploration of the functional consequences of fixational eye movements in the absence of a fovea.

A recent theory posits that ocular drifts of fixational eye movements serve to reformat the visual input of natural images, so that the power of the input image is equalized across a range of spatial frequencies. This "spectral whitening" effect is postulated to improve the processing of high-spatial-frequency information and requires normal fixational eye movements. Given that people with macular disease exhibit abnormal fixational eye movements, do they also exhibit spectral whitening? To answer this question, we computed the power spectral density of movies of natural images translated in space and time according to the fixational eye movements (thus simulating the retinal input) of a group of observers with long-standing bilateral macular disease. Just as for people with normal vision, the power of the retinal input at low spatial frequencies was lower than that based on the 1/f2 relationship, demonstrating spectral whitening. However, the amount of whitening was much less for observers with macular disease when compared with age-matched controls with normal vision. A mediation analysis showed that the eccentricity of the preferred retinal locus adopted by these observers and the characteristics of ocular drifts are important factors limiting the amount of whitening. Finally, we did not find a normal aging effect on spectral whitening. Although these findings alone cannot form a causal link between macular disease and spectral properties of eye movements, they suggest novel potential means of modifying the characteristics of fixational eye movements, which may in turn improve functional vision for people with macular disease

Clinical Applications of Stochastic Dynamic Models of the Brain, Part II: A Review

Brain activity derives from intrinsic dynamics (due to neurophysiology and anatomical connectivity) in concert with stochastic effects that arise from sensory fluctuations, brainstem discharges, and random microscopic states such as thermal noise. The dynamic evolution of systems composed of both dynamic and random fluctuations can be studied with stochastic dynamic models (SDMs). This article, Part II of a two-part series, reviews applications of SDMs to large-scale neural systems in health and disease. Stochastic models have already elucidated a number of pathophysiological phenomena, such as epilepsy and hypoxic ischemic encephalopathy, although their use in biological psychiatry remains rather nascent. Emerging research in this field includes phenomenological models of mood fluctuations in bipolar disorder and biophysical models of functional imaging data in psychotic and affective disorders. Together with deeper theoretical considerations, this work suggests that SDMs will play a unique and influential role in computational psychiatry, unifying empirical observations with models of perception and behavior

Computational models of the thalamocortical circuit: sleep oscillations and receptive fields.

The thalamus is a subcortical structure, which consists of a collection of functionally and morphologically defined nuclei. A subset of these, the sensory nuclei, receive information from the periphery and relay it to the related primary cortical area. Hence the thalamus was traditionaUy assumed to passively relay afferent information. However, the fact that thalamic relay cells receive a large proportion of their sjoiaptic inputs from the cortical cells to which they project, has led to the consensus that there is a more significant thalamic contribution to sensory processing. This thesis investigates the role of the thalamocortical feedback loop using population-level computational models. In particular two states of thalamocortical activity are investigated: early sleep, and active visual processing. During early sleep, the network displays 7-14Hz spindle oscillations. These osciUations have been previously modelled using conductance-based paradigms, but here the activity is investigated through the nonhnear dynamics of the circuitry. It is shown that the circuit has an intrinsic resonant frequency in the spindles range. During visual processing, the role of the lateral geniculate nucleus (the primary visual thalamic nucleus) was previously overlooked, as thalamic receptive fields are spatially identical to those in the retina. Temporally however, thalamic and retinal responses differ in magnitude, and the second model in this thesis shows how cortical feedback can have a role in augmenting thalamic temporal responses. This model was reduced in order to find the minimal thalamic circuitry that can produce such responses, and this final model can also exhibit steady state oscillatory behaviour. The transition from transient visual activity to sustained oscillatory activity in this model, required a switch in the relative cortical feedback weights to the thalamocortical and the reticular populations. Together, these results indicate that the contribution of the thalamus to neural activity can no longer be ignored

Biological and Behavioural Markers of Parkinson’s Disease

Today, upwards of 10 million people—approximately 9 500 of whom reside in New Zealand—are living with Parkinson’s disease (PD). Yet, the means of diagnosing PD remain somewhat similar to those available to James Parkinson in 1817. Recently, however, there has been an increasing interest in the role of biomarkers in PD; these, in turn, are hoped to provide the necessary means by which PD can be diagnosed earlier, treated better and—ultimately—altogether prevented and/or cured. Given the multifaceted nature of the aetiology underlying PD, a “multi-system” approach to biomarkers is more likely to yield fruitful results. Thus, the overarching aim of this study was to explore several biomarkers (within two realms—biological and behavioural) that may be used at different time-points as the disease progresses. In the biological markers trials, biofluid samples (i.e., cerebrospinal fluid ‘CSF’ and plasma) were obtained from 11 patients with PD. Analyses of these samples did not detect any blackcurrant anthocyanins either before or after oral supplementation with blackcurrant concentrate for four weeks. Consumption of blackcurrant concentrate, however, significantly increased the CSF concentration of cyclic glycine-proline. This led to the hypothesis of an indirect mechanism underlying the putative benefit of berry-fruit consumption on the risk of developing PD—perhaps through modulating the peripheral resistance to insulinlike growth factor-1 otherwise observed in patients with PD. CSF concentrations of the aminoterminal fragment of C-type natriuretic peptide were significantly lower in PD patients than the reported range from a group of pre-operative orthopaedic patients. Finally, the obtained samples were utilised to characterise the profile of exosomes present in the CSF and plasma of PD patients. The three patients with the highest plasma exosome concentrations also had the lowest scores on the Montreal Cognitive Assessment. The behavioural markers study investigated biomarkers in patients with established PD—a stage when cognition may become involved. The emphasis was to obtain an in-depth evaluation of novel eye movement-performance associations. In general, no remarkable differences in eye movement parameters were noted among the three study groups (n = 16 per group): PD with normal cognition (PDN), PD with mild cognitive impairment (PD-MCI) and matched controls (NC) in natural and laboratory-based neuropsychological tasks. This indicates a relatively preserved organisation of neuropsychological task performance as evident from eye movements among the participants. In addition, some insights into human behaviour on several tasks were gained. In the animal naming task, participants from all three groups tended to fixate on the animal’s head in order to name it. Participants also fixated on the distal ends of lines when attempting the Judgement of Line Orientation task. PD-MCI participants were found to make significantly more vertical saccades when searching the Where’s Wally?™ Maze task in comparison with NC and PD-N participants. On the Symbol Digit Modalities Test, PD-MCI participants scored significantly lower than NC and PDN participants. Finally, task organisation of the tea-making task was mostly consistent among the study participants; PD participants (of both groups) executed the task significantly slower than NC participants. Given the relatively small sample sizes, an exploratory approach was generally taken. To gain confidence in the results of individual findings, further research ought to be carried out in order to exclude the possibility of sampling variability accounting for the reported observations