Traumatic brain injury promotes neurogenesis at the cost of astrogliogenesis in the adult hippocampus of male mice.

Traumatic brain injury (TBI) can result in long-lasting changes in hippocampal function. The changes induced by TBI on the hippocampus contribute to cognitive deficits. The adult hippocampus harbors neural stem cells (NSCs) that generate neurons (neurogenesis), and astrocytes (astrogliogenesis). While deregulation of hippocampal NSCs and neurogenesis have been observed after TBI, it is not known how TBI may affect hippocampal astrogliogenesis. Using a controlled cortical impact model of TBI in male mice, single cell RNA sequencing and spatial transcriptomics, we assessed how TBI affected hippocampal NSCs and the neuronal and astroglial lineages derived from them. We observe an increase in NSC-derived neuronal cells and a concomitant decrease in NSC-derived astrocytic cells, together with changes in gene expression and cell dysplasia within the dentate gyrus. Here, we show that TBI modifies NSC fate to promote neurogenesis at the cost of astrogliogenesis and identify specific cell populations as possible targets to counteract TBI-induced cellular changes in the adult hippocampus.

Diagnosis from fundus photographs.

AIM: To investigate the way in which ophthalmologists observe fundi and make diagnoses from their observations. METHODS: A set of 12 test photographs was presented to 9 ophthalmologists. The subjects were asked to identify the features in the photographs that are important for forming a diagnosis and were also asked to form differential diagnoses. The scanpaths of the subjects were recorded during their inspection of the photographs. Subsequently, they were asked to trace over the important features of four of the photographs. RESULTS: The correctness of the diagnoses was described by weighted numerical scores. Differential diagnoses made after 30 s of inspection were significantly better than those made after 5 s. Irrespective of correctness, the reported diagnoses were dominated by the most obvious features of the photograph. Incorrect diagnoses were made either because the subjects failed to identify the significant features of the photograph or because they failed to comprehend the significance of the identified features. CONCLUSION: Accurate funduscopy involves both perception of diagnostic features and cognitive interpretation of these features. Verbal reports, eye movement recordings and tracings reveal the features and interpretations used to make a diagnosis. These techniques will be used in a subsequent study to evaluate the relative contributions of formal training and experience to the development of diagnostic skills.

Nonlinear time series analysis of jerk congenital nystagmus.

Nonlinear dynamics provides a complementary framework to control theory for the quantitative analysis of the oculomotor control system. This paper presents a number of findings relating to the aetiology and mechanics of the pathological ocular oscillation jerk congenital nystagmus (jerk CN). A range of time series analysis techniques were applied to recorded jerk CN waveforms, and also to simulated jerk waveforms produced by an established model in which the oscillations are a consequence of an unstable neural integrator. The results of the analysis were then interpreted within the framework of a generalised model of the unforced oculomotor system.This work suggests that for jerk oscillations, the origin of the instability lies in one of the five oculomotor subsystems, rather than in the final common pathway (the neural integrator and muscle plant). Additionally, experimental estimates of the linearised foveation dynamics imply that a refixating fast phase induced by a near-homoclinic trajectory will result in periodic oscillations. Local dimension calculations show that the dimension of the experimental jerk CN data increases during the fast phase, indicating that the oscillations are not periodic, and hence that the refixation mechanism is of greater complexity than a homoclinic reinjection. The dimension increase is hypothesised to result either from a signal-dependent noise process in the saccadic system, or the activation of additional oculomotor components at the beginning of the fast phase. The modification of a recent saccadic system model to incorporate biologically realistic signal-dependent noise is suggested, in order to test the first of these hypotheses.

The achiasmia spectrum: congenitally reduced chiasmal decussation.

AIM: To describe the clinical spectrum of achiasmia, a congenital disorder of reduced relative decussation at the optic chiasm. METHODS: A retrospective case note and patient review of nine children (four boys). Achiasmia was defined by the combination of a characteristic asymmetry of the monocular visual evoked potential (VEP) response to flash and neuroimaging showing reduced chiasmal size. RESULTS: Three of the children had an associated skull base encephalocele with agenesis of the corpus callosum. In two patients achiasmia was associated with septo-optic dysplasia. Three patients had no neuroimaging abnormalities other than reduced chiasmal size and have no known pituitary dysfunction. One child had multiple physical deformities but the only brain imaging abnormality was reduced chiasmal size. CONCLUSIONS: Some children with disorders of midline central nervous system development, including septo-optic dysplasia and skull base encephaloceles, have congenitally reduced chiasmal decussation. Reduced relative decussation may co-exist with overall chiasmal hypoplasia. Children with an apparently isolated chiasmal decussation deficit may have other subtle neurological findings, but our clinical impression is that most of these children function well.

Eye movement instabilities and nystagmus can be predicted by a nonlinear dynamics model of the saccadic system.

The study of eye movements and oculomotor disorders has, for four decades, greatly benefitted from the application of control theoretic concepts. This paper is an example of a complementary approach based on the theory of nonlinear dynamical systems. Recently, a nonlinear dynamics model of the saccadic system was developed, comprising a symmetric piecewise-smooth system of six first-order autonomous ordinary differential equations. A preliminary numerical investigation of the model revealed that in addition to generating normal saccades, it could also simulate inaccurate saccades, and the oscillatory instability known as congenital nystagmus (CN). By varying the parameters of the model, several types of CN oscillations were produced, including jerk, bidirectional jerk and pendular nystagmus. The aim of this study was to investigate the bifurcations and attractors of the model, in order to obtain a classification of the simulated oculomotor behaviours. The application of standard stability analysis techniques, together with numerical work, revealed that the equations have a rich bifurcation structure. In addition to Hopf, homoclinic and saddlenode bifurcations organised by a Takens-Bogdanov point, the equations can undergo nonsmooth pitchfork bifurcations and nonsmooth gluing bifurcations. Evidence was also found for the existence of Hopf-initiated canards. The simulated jerk CN waveforms were found to correspond to a pair of post-canard symmetry-related limit cycles, which exist in regions of parameter space where the equations are a slow-fast system. The slow and fast phases of the simulated oscillations were attributed to the geometry of the corresponding slow manifold. The simulated bidirectional jerk and pendular waveforms were attributed to a symmetry invariant limit cycle produced by the gluing of the asymmetric cycles. In contrast to control models of the oculomotor system, the bifurcation analysis places clear restrictions on which kinds of behaviour are likely to be associated with each other in parameter space, enabling predictions to be made regarding the possible changes in the oscillation type that may be observed upon changing the model parameters. The analysis suggests that CN is one of a range of oculomotor disorders associated with a pathological saccadic braking signal, and that jerk and pendular nystagmus are the most probable oscillatory instabilities. Additionally, the transition from jerk CN to bidirectional jerk and pendular nystagmus observed experimentally when the gaze angle or attention level is changed is attributed to a gluing bifurcation. This suggests the possibility of manipulating the waveforms of subjects with jerk CN experimentally to produce waveforms with an extended foveation period, thereby improving visual resolution.

The characteristics of dynamic overshoots in square-wave jerks, and in congenital and manifest latent nystagmus.

Dynamic overshoots are seen after voluntary re-fixation saccades. They are microsaccadic movements which follow primary saccades and have no delay. The purpose of this study was to examine the prevalence and metrics of the dynamic overshoots seen after involuntary saccades. Using infra-red oculography we demonstrate that dynamic overshoots are a common occurrence in physiological square-wave jerks, congenital nystagmus and manifest latent nystagmus and that these overshoots are saccadic in nature and have the same dynamic characteristics as those seen following voluntary saccades. It is therefore likely that they share common neural commands to those dynamic overshoots seen after a volitional saccade. All dynamic overshoots are postulated to be the unwanted consequence of making a saccade and are simulated in a model of fast oculomotor behaviour which is consistent with known experimental results.

Modelling of congenital nystagmus waveforms produced by saccadic system abnormalities.

Models of the mechanisms of normal eye movements are typically described in terms of the block diagrams which are used in control theory. An alternative approach to understanding the mechanisms of normal eye movements involves describing the eye movement behaviour in terms of smooth changes in state variables. The latter approach captures the burst cell firing against motor error (difference between target gaze angle and current gaze angle) phase plane behaviour which is found experimentally and facilitates the modelling of variations in burst cell behaviour. A novel explanation of several types of congenital nystagmus waveforms is given in terms of a saccadic termination abnormality.

Dynamical systems analysis: a new method of analysing congenital nystagmus waveforms.

Congenital nystagmus is an oculomotor disorder in which fixation is disrupted by rhythmical, bilateral involuntary oscillations. Clinically these eye movements have been described with some degree of success in terms of their peak-to-peak amplitude, frequency, mean velocity and waveform shape. However, it has not proved possible to diagnose any underlying pathology from the nystagmus characteristics. Here, we propose a new approach to understanding the nystagmus using dynamical systems theory. Our approach is based on the use of delay embedding techniques, which allow one to relate a time series of scalar observations to the state space dynamics of the underlying dynamical system. Using this approach we quantify the dynamics of the nystagmus in the region of foveation and present evidence to suggest that it is low-dimensional and deterministic. Our results put new constraints on acceptable models of nystagmus and suggest a way to make a closer link between data analysis and model development. This approach raises the hope that techniques originally developed to stabilise chaotic systems, by using small perturbations, may prove useful in the control of nystagmus.

Apparent shape of the Mach book.

The Mach book is a two-dimensional figure which looks three-dimensional. Despite the impression of depth in the figure, the apparent shape has not been determined. It has been suggested that the book appears as part of a 'cubic corner', 'as flat as possible', or with each half rotated about its long diagonal. Alternative hypotheses as to the three-dimensional orientation of the book were tested by means of a probe-line technique. It was found that, although no hypothesis matched the results of all of the subjects, the probe-line settings of individual subjects were approximately linear or piecewise linear functions of the angles in the picture. The technique was also applied to asymmetric versions of the figure and it was found that the subjects modified their settings in accord with the constraint that the two halves of the figure must join in depth along their common edge. The findings are in agreement with models of the interpretation of line drawings in which local estimates of edge orientation in depth are formed, and subsequently checked for consistency.

Gaze angle explanations of the induced effect.

Mayhew and Longuet-Higgins formulated a computational explanation of the induced effect which successfully predicts the conditions under which the induced effect will occur. Underlying their theories are the assumptions that disparity information is separated into horizontal and vertical components and that the vertical disparities are used to calculate the gaze angles. An implementation of the fusional explanation introduced by Petrov makes similar predictions for the induced effect, but does not depend on these two assumptions.

Natural coordinates for specification of eye movements.

Tweed and Vilis (Journal of Neurophysiology, 58, 832-849, 1987) have argued that quaternion algebra provides the most appropriate description of the rotations of the eye, and have derived a three-dimensional model of gaze control based on quaternion operations. Euler angles give a simpler description of the rotations of the eye, and can also be used to formulate an alternative version of the three-dimensional gaze control model. Comparison of the two versions of the model highlights the distinction between the functional predictions of the model, and the predictions which depend only on the choice of mathematical descriptions.

An extension of Helmholtz's explanation of Listing's law.

Helmoholtz argued that the eye moves in accordance with Listing's law to ensure that objects have the same apparent direction despite changes in the point of fixation. Listing's law ensures that the same pattern of image displacements is associated with a given eye movement, independent of the initial point of fixation. His explanation has been extended to the problem of ensuring that objects remain at the same apparent depth, with both direct and indirect fixation. This problem is simplified if disparity is analysed in the region of the frontal plane.

Computed extraocular muscle activity during blinks.

The rotations and retractions of the eyeball due to co-contraction of the extraocular muscles are investigated using a model of the mechanics of the orbital plant. The hypothesis that the rotational movements are secondary to globe retraction is not supported.

An investigation of trained neural networks from a neurophysiological perspective.

The application of theoretical neural networks to preprocessed images was investigated with the aim of developing a computational recognition system. The neural networks were trained by means of a back-propagation algorithm, to respond selectively to computer-generated bars and edges. The receptive fields of the trained networks were then mapped, in terms of both their synaptic weights and their responses to spot stimuli. There was a direct relationship between the pattern of weights on the inputs to the hidden units (the units in the intermediate layer between the input and the output units), and their receptive field as mapped by spot stimuli. This relationship was not sustained at the level of the output units in that their spot-mapped responses failed to correspond either with the weights of the connections from the hidden units to the output units, or with a qualitative analysis of the networks. Part of this discrepancy may be ascribed to the output function used in the back-propagation algorithm.

Normal visual pathway routing in dissociated vertical deviation.

Flash visually evoked cortical potentials have been recorded in three groups of age- and sex-matched subjects; one comprised of subjects with dissociated vertical deviation, one comprised of subjects with oculocutaneous albinism and one group of controls. The latency of the major positive (P2) component did not show statistically significant contralateral lateralization on monocular stimulation in either the dissociated vertical deviation group or the control group. Contralateral lateralization was found in the albino group at a statistically significant level (P less than 0.01). It is concluded that subjects with dissociated vertical deviation do not possess the typical albino optic pathway misrouting that has been reported.

Excursion tests of ocular motility.

Three alternative excursion tests of ocular motility have been compared. A computer model of the mechanics of the extraocular muscles has been used to estimate the tensions developed by the muscles in these tests. On the basis of these calculations we recommend the transverse test in which the positions of the eyes are observed as they track a target moving from the right to the left with a fixed elevation and a fixed depression.

A method for raytracing through schematic eyes with off-axis components.

A linear algebraic method for tracing skew rays through aspheric surfaces is described. The advantage of this method is that the refracting surfaces can be translated and rotated with respect to each other. The method is used to investigate the optical factors affecting the location of Purkinje images.

A schematic eye model for the effects of translation and rotation of ocular components on peripheral astigmatism.

The relative contributions of translation and rotation of the cornea and lens to peripheral astigmatic asymmetry have been investigated using a linear algebraic ray tracing method. It is believed that lenticular rotation is responsible for angle alpha, so bringing about peripheral astigmatic asymmetry, as normally occurs in human eyes over the temporal and nasal retina. Rotation of the cornea may be responsible for the small numbers of eyes which exhibit large amounts of peripheral astigmatic asymmetry. The effects of corneal rotation and translation on the dimensions of the entrance pupil are illustrated.

A model for retinal shape changes in ametropia.

Modeling ametropic retinal shape changes with an ellipsoid of constant equatorial radius has been found to produce types of peripheral astigmatism which are in good agreement with experimental findings.