Neural Network Evidence for the Coupling of Presaccadic Visual Remapping to Predictive Eye Position Updating.

As we look around a scene, we perceive it as continuous and stable even though each saccadic eye movement changes the visual input to the retinas. How the brain achieves this perceptual stabilization is unknown, but a major hypothesis is that it relies on presaccadic remapping, a process in which neurons shift their visual sensitivity to a new location in the scene just before each saccade. This hypothesis is difficult to test in vivo because complete, selective inactivation of remapping is currently intractable. We tested it in silico with a hierarchical, sheet-based neural network model of the visual and oculomotor system. The model generated saccadic commands to move a video camera abruptly. Visual input from the camera and internal copies of the saccadic movement commands, or corollary discharge, converged at a map-level simulation of the frontal eye field (FEF), a primate brain area known to receive such inputs. FEF output was combined with eye position signals to yield a suitable coordinate frame for guiding arm movements of a robot. Our operational definition of perceptual stability was "useful stability," quantified as continuously accurate pointing to a visual object despite camera saccades. During training, the emergence of useful stability was correlated tightly with the emergence of presaccadic remapping in the FEF. Remapping depended on corollary discharge but its timing was synchronized to the updating of eye position. When coupled to predictive eye position signals, remapping served to stabilize the target representation for continuously accurate pointing. Graded inactivations of pathways in the model replicated, and helped to interpret, previous in vivo experiments. The results support the hypothesis that visual stability requires presaccadic remapping, provide explanations for the function and timing of remapping, and offer testable hypotheses for in vivo studies. We conclude that remapping allows for seamless coordinate frame transformations and quick actions despite visual afferent lags. With visual remapping in place for behavior, it may be exploited for perceptual continuity.

Eye movements in children during reading : a review

L’analyse des mouvements des yeux a été très largement utilisée ces dernières années en psychologie de la lecture pour mieux rendre compte des traitements cognitifs sous-jacents. Cependant, cette technique a été jusqu’à présent peu utilisée dans une perspective développementale, pour mieux comprendre les processus d’apprentissage et de la lecture chez les enfants. Ce chapitre présente une brève revue des études qui ont comparé les mouvements des yeux chez les enfants à ceux des adultes. Nous y décrivons dans un premier temps ce qui distingue les patterns oculaires de ces deux populations, et présentons ensuite les résultats d’études tentant d’expliquer ces différences en terme de contraintes oculomotrices, visuelles et linguistiques.

Effects of visuospatial tasks on desensitization to emotive memories

Objectives. Intrusive memories of extreme trauma can disrupt a stepwise approach to imaginal exposure. Concurrent tasks that load the visuospatial sketchpad (VSSP) of working memory reduce the vividness of recalled images. This study tested whether relief of distress from competing VSSP tasks during imaginal exposure is at the cost of impaired desensitization . Design. This study examined repeated exposure to emotive memories using 18 unselected undergraduates and a within-subjects design with three exposure conditions (Eye Movement, Visual Noise, Exposure Alone) in random, counterbalanced order. Method. At baseline, participants recalled positive and negative experiences, and rated the vividness and emotiveness of each image. A different positive and negative recollection was then used for each condition. Vividness and emotiveness were rated after each of eight exposure trials. At a post-exposure session 1 week later, participants rated each image without any concurrent task. Results. Consistent with previous research, vividness and distress during imaging were lower during Eye Movements than in Exposure Alone, with passive visual interference giving intermediate results. A reduction in emotional responses from Baseline to Post was of similar size for the three conditions. Conclusion. Visuospatial tasks may offer a temporary response aid for imaginal exposure without affecting desensitization.

The effect of Amblyopia on motor and psychosocial skills in children

Background/Aims: In an investigation of the functional impact of amblyopia on children, the fine motor skills, perceived self-esteem and eye movements of amblyopic children were compared with that of age-matched controls. The influence of amblyogenic condition or treatment factors that might predict any decrement in outcome measures was investigated. The relationship between indirect measures of eye movements that are used clinically and eye movement characteristics recorded during reading was examined and the relevance of proficiency in fine motor skills to performance on standardised educational tests was explored in a sub-group of the control children. Methods: Children with amblyopia (n=82; age 8.2 ± 1.3 years) from differing causes (infantile esotropia n=17, acquired strabismus n=28, anisometropia n=15, mixed n=13 and deprivation n=9), and a control group of children (n=106; age 9.5 ± 1.2 years) participated in this study. Measures of visual function included monocular logMAR visual acuity (VA) and stereopsis assessed with the Randot Preschool Stereoacuity test, while fine motor skills were measured using the Visual-Motor Control (VMC) and Upper Limb Speed and Dexterity (ULSD) subtests of the Brunicks-Oseretsky Test of Motor Proficiency. Perceived self esteem was assessed for those children from grade 3 school level with the Harter Self Perception Profile for Children and for those in younger grades (preschool to grade 2) with the Pictorial Scale of Perceived Competence and Acceptance for Young Children. A clinical measure of eye movements was made with the Developmental Eye Movement (DEM) test for those children aged eight years and above. For appropriate case-control comparison of data, the results from amblyopic children were compared with age-matched sub-samples drawn from the group of children with normal vision who completed the tests. Eye movements during reading for comprehension were recorded by the Visagraph infra-red recording system and results of standardised tests of educational performance were also obtained for a sub-set of the control group. Results Amblyopic children (n=82; age 8.2 ± 1.7 years) performed significantly poorer than age-matched control children (n=37; age 8.3 ± 1.3 years) on 9 of 16 fine motor skills sub-items and for the overall age-standardised scores for both VMC and ULSD items (p<0.05); differences were most evident on timed manual dexterity tasks. The underlying aetiology of amblyopia and level of stereoacuity significantly affected fine motor skill performance on both items. However, when examined in a multiple regression model that took into account the inter-correlation between visual characteristics, poorer fine motor skills performance was only associated with strabismus (F1,75 = 5.428; p =0. 022), and not with the level of stereoacuity, refractive error or visual acuity in either eye. Amblyopic children from grade 3 school level and above (n=47; age 9.2 ± 1.3 years), particularly those with acquired strabismus, had significantly lower social acceptance scores than age-matched control children (n=52; age 9.4 ± 0.5 years) (F(5,93) = 3.14; p = 0.012). However, the scores of the amblyopic children were not significantly different to controls for other areas related to self-esteem, including scholastic competence, physical appearance, athletic competence, behavioural conduct and global self worth. A lower social acceptance score was independently associated with a history of treatment with patching but not with a history of strabismus or wearing glasses. Amblyopic children from pre-school to grade 2 school level (n=29; age = 6.6 ± 0.6 years) had similar self-perception scores to their age-matched peers (n=20; age = 6.4 ± 0.5 years). There were no significant differences between the amblyopic (n=39; age 9.1 ± 0.9 years) and age-matched control (n = 42; age = 9.3 ± 0.38 years) groups for any of the DEM outcome measures (Vertical Time, Horizontal Time, Number of Errors and Ratio (Horizontal time/Vertical time)). Performance on the DEM did not significantly relate to measures of VA in either eye, level of binocular function, history of strabismus or refractive error. Developmental Eye Movement test outcome measures Horizontal Time and Vertical Time were significantly correlated with reading rates measured by the Visagraph for both reading for comprehension and naming numbers (r>0.5). Some moderate correlations were also seen between the DEM Ratio and word reading rates as recorded by Visagraph (r=0.37). In children with normal vision, academic scores in mathematics, spelling and reading were associated with measures of fine motor skills. Strongest effect sizes were seen with the timed manual dexterity domain, Upper Limb Speed and Dexterity. Conclusions Amblyopia may have a negative impact on a child’s fine motor skills and an older child’s sense of acceptance by their peers may be influenced by treatment that includes eye patching. Clinical measures of eye movements were not affected in amblyopic children. A number of the outcome measures of the DEM are associated with objective recordings of reading rates, supporting its clinical use for identification of children with slower reading rates. In children with normal vision, proficiency on clinical measures of fine motor skill are associated with outcomes on standardised measures of educational performance. Scores on timed manual dexterity tasks had the strongest association with educational performance. Collectively, the results of this study indicate that, in addition to the reduction in visual acuity and binocular function that define the condition, amblyopes have functional impairment in childhood development skills that underlie proficiency in everyday activities. The study provides support for strategies aimed at early identification and remediation of amblyopia and the co-morbidities that arise from abnormal visual neurodevelopment.

The impact of presbyopic spectacles and contact lenses on driving performance

Presbyopia affects individuals from the age of 45 years onwards, resulting in difficulty in accurately focusing on near objects. There are many optical corrections available including spectacles or contact lenses that are designed to enable presbyopes to see clearly at both far and near distances. However, presbyopic vision corrections also disturb aspects of visual function under certain circumstances. The impact of these changes on activities of daily living such as driving are, however, poorly understood. Therefore, the aim of this study was to determine which aspects of driving performance might be affected by wearing different types of presbyopic vision corrections. In order to achieve this aim, three experiments were undertaken. The first experiment involved administration of a questionnaire to compare the subjective driving difficulties experienced when wearing a range of common presbyopic contact lens and spectacle corrections. The questionnaire was developed and piloted, and included a series of items regarding difficulties experienced while driving under day and night-time conditions. Two hundred and fifty five presbyopic patients responded to the questionnaire and were categorised into five groups, including those wearing no vision correction for driving (n = 50), bifocal spectacles (BIF, n = 54), progressive addition lenses spectacles (PAL, n = 50), monovision (MV, n = 53) and multifocal contact lenses (MTF CL, n = 48). Overall, ratings of satisfaction during daytime driving were relatively high for all correction types. However, MV and MTF CL wearers were significantly less satisfied with aspects of their vision during night-time than daytime driving, particularly with regard to disturbances from glare and haloes. Progressive addition lens wearers noticed more distortion of peripheral vision, while BIF wearers reported more difficulties with tasks requiring changes in focus and those who wore no vision correction for driving reported problems with intermediate and near tasks. Overall, the mean level of satisfaction for daytime driving was quite high for all of the groups (over 80%), with the BIF wearers being the least satisfied with their vision for driving. Conversely, at night, MTF CL wearers expressed the least satisfaction. Research into eye and head movements has become increasingly of interest in driving research as it provides a means of understanding how the driver responds to visual stimuli in traffic. Previous studies have found that wearing PAL can affect eye and head movement performance resulting in slower eye movement velocities and longer times to stabilize the gaze for fixation. These changes in eye and head movement patterns may have implications for driving safety, given that the visual tasks for driving include a range of dynamic search tasks. Therefore, the second study was designed to investigate the influence of different presbyopic corrections on driving-related eye and head movements under standardized laboratory-based conditions. Twenty presbyopes (mean age: 56.1 ± 5.7 years) who had no experience of wearing presbyopic vision corrections, apart from single vision reading spectacles, were recruited. Each participant wore five different types of vision correction: single vision distance lenses (SV), PAL, BIF, MV and MTF CL. For each visual condition, participants were required to view videotape recordings of traffic scenes, track a reference vehicle and identify a series of peripherally presented targets while their eye and head movements were recorded using the faceLAB® eye and head tracking system. Digital numerical display panels were also included as near visual stimuli (simulating the visual displays of a vehicle speedometer and radio). The results demonstrated that the path length of eye movements while viewing and responding to driving-related traffic scenes was significantly longer when wearing BIF and PAL than MV and MTF CL. The path length of head movements was greater with SV, BIF and PAL than MV and MTF CL. Target recognition was less accurate when the near stimulus was located at eccentricities inferiorly and to the left, rather than directly below the primary position of gaze, regardless of vision correction type. The third experiment aimed to investigate the real world driving performance of presbyopes while wearing different vision corrections measured on a closed-road circuit at night-time. Eye movements were recorded using the ASL Mobile Eye, eye tracking system (as the faceLAB® system proved to be impractical for use outside of the laboratory). Eleven participants (mean age: 57.25 ± 5.78 years) were fitted with four types of prescribed vision corrections (SV, PAL, MV and MTF CL). The measures of driving performance on the closed-road circuit included distance to sign recognition, near target recognition, peripheral light-emitting-diode (LED) recognition, low contrast road hazards recognition and avoidance, recognition of all the road signs, time to complete the course, and driving behaviours such as braking, accelerating, and cornering. The results demonstrated that driving performance at night was most affected by MTF CL compared to PAL, resulting in shorter distances to read signs, slower driving speeds, and longer times spent fixating road signs. Monovision resulted in worse performance in the task of distance to read a signs compared to SV and PAL. The SV condition resulted in significantly more errors made in interpreting information from in-vehicle devices, despite spending longer time fixating on these devices. Progressive addition lenses were ranked as the most preferred vision correction, while MTF CL were the least preferred vision correction for night-time driving. This thesis addressed the research question of how presbyopic vision corrections affect driving performance and the results of the three experiments demonstrated that the different types of presbyopic vision corrections (e.g. BIF, PAL, MV and MTF CL) can affect driving performance in different ways. Distance-related driving tasks showed reduced performance with MV and MTF CL, while tasks which involved viewing in-vehicle devices were significantly hampered by wearing SV corrections. Wearing spectacles such as SV, BIF and PAL induced greater eye and head movements in the simulated driving condition, however this did not directly translate to impaired performance on the closed- road circuit tasks. These findings are important for understanding the influence of presbyopic vision corrections on vision under real world driving conditions. They will also assist the eye care practitioner to understand and convey to patients the potential driving difficulties associated with wearing certain types of presbyopic vision corrections and accordingly to support them in the process of matching patients to optical corrections which meet their visual needs.

The effect of presbyiopic vision corrections on nighttime driving performance

Purpose. To investigate the effect of various presbyopic vision corrections on nighttime driving performance on a closed-road driving circuit. Methods. Participants were 11 presbyopes (mean age, 57.3 ± 5.8 years), with a mean best sphere distance refractive error of R+0.23±1.53 DS and L+0.20±1.50 DS, whose only experience of wearing presbyopic vision correction was reading spectacles. The study involved a repeated-measures design by which a participant's nighttime driving performance was assessed on a closed-road circuit while wearing each of four power-matched vision corrections. These included single-vision distance lenses (SV), progressive-addition spectacle lenses (PAL), monovision contact lenses (MV), and multifocal contact lenses (MTF CL) worn in a randomized order. Measures included low-contrast road hazard detection and avoidance, road sign and near target recognition, lane-keeping, driving time, and legibility distance for street signs. Eye movement data (fixation duration and number of fixations) were also recorded. Results. Street sign legibility distances were shorter when wearing MV and MTF CL than SV and PAL (P < 0.001), and participants drove more slowly with MTF CL than with PALs (P = 0.048). Wearing SV resulted in more errors (P < 0.001) and in more (P = 0.002) and longer (P < 0.001) fixations when responding to near targets. Fixation duration was also longer when viewing distant signs with MTF CL than with PAL (P = 0.031). Conclusions. Presbyopic vision corrections worn by naive, unadapted wearers affected nighttime driving. Overall, spectacle corrections (PAL and SV) performed well for distance driving tasks, but SV negatively affected viewing near dashboard targets. MTF CL resulted in the shortest legibility distance for street signs and longer fixation times.

The effect of simulated astigmatic refractive error on reading performance

Background: Few studies have specifically investigated the functional effects of uncorrected astigmatism on measures of reading fluency. This information is important to provide evidence for the development of clinical guidelines for the correction of astigmatism. Methods: Participants included 30 visually normal, young adults (mean age 21.7 ± 3.4 years). Distance and near visual acuity and reading fluency were assessed with optimal spectacle correction (baseline) and for two levels of astigmatism, 1.00DC and 2.00DC, at two axes (90° and 180°) to induce both against-the-rule (ATR) and with-the-rule (WTR) astigmatism. Reading and eye movement fluency were assessed using standardized clinical measures including the test of Discrete Reading Rate (DRR), the Developmental Eye Movement (DEM) test and by recording eye movement patterns with the Visagraph (III) during reading for comprehension. Results: Both distance and near acuity were significantly decreased compared to baseline for all of the astigmatic lens conditions (p < 0.001). Reading speed with the DRR for N16 print size was significantly reduced for the 2.00DC ATR condition (a reduction of 10%), while for smaller text sizes reading speed was reduced by up to 24% for the 1.00DC ATR and 2.00DC condition in both axis directions (p<0.05). For the DEM, sub-test completion speeds were significantly impaired, with the 2.00DC condition affecting both vertical and horizontal times and the 1.00DC ATR condition affecting only horizontal times (p<0.05). Visagraph reading eye movements were not significantly affected by the induced astigmatism. Conclusions: Induced astigmatism impaired performance on selected tests of reading fluency, with ATR astigmatism having significantly greater effects on performance than did WTR, even for relatively small amounts of astigmatic blur of 1.00DC. These findings have implications for the minimal prescribing criteria for astigmatic refractive errors.

Impact of simulated hyperopia on academic-related performance in children

Purpose: To investigate the impact of simulated hyperopia and sustained near work on children’s ability to perform a range of academic-related tasks. Methods: Fifteen visually normal children (mean age: 10.9 ± 0.8 years; 10 males and 5 females) were recruited. Performance on a range of standardised academic-related outcome measures was assessed with and without 2.50 D of simulated bilateral hyperopia (administered in a randomised order), before and after 20 minutes of sustained near work, at two separate testing sessions. Academic-related measures included a standardised reading test (the Neale Analysis of Reading Ability), visual information processing tests (Coding and Symbol Search subtests from the Wechsler Intelligence Scale for Children) and a reading-related eye movement test (the Developmental Eye Movement test). Results: Simulated bilateral hyperopia and sustained near work each independently impaired reading, visual information processing and reading-related eye movement performance (p<0.001). A significant interaction was also demonstrated between these factors (p<0.001), with the greatest decrement in performance observed when simulated hyperopia was combined with sustained near work. This combination resulted in performance reductions of between 5% and 24% across the range of academic-related measures. A significant moderate correlation was also found between the change in horizontal near heterophoria and the change in several of the academic-related outcome measures, following the addition of simulated hyperopia. Conclusions: A relatively low level of simulated bilateral hyperopia impaired children’s performance on a range of academic–related outcome measures, with sustained near work further exacerbating this effect. Further investigations are required to determine the impact of correcting low levels of hyperopia on academic performance in children.

Simulated astigmatism impairs academic-related performance in children

Purpose: Astigmatism is an important refractive condition in children. However, the functional impact of uncorrected astigmatism in this population is not well established, particularly with regard to academic performance. This study investigated the impact of simulated bilateral astigmatism on academic-related tasks before and after sustained near work in children. Methods: Twenty visually normal children (mean age: 10.8 ± 0.7 years; 6 males and 14 females) completed a range of standardised academic-related tests with and without 1.50 D of simulated bilateral astigmatism (with both academic-related tests and the visual condition administered in a randomised order). The simulated astigmatism was induced using a positive cylindrical lens while maintaining a plano spherical equivalent. Performance was assessed before and after 20 minutes of sustained near work, during two separate testing sessions. Academic-related measures included a standardised reading test (the Neale Analysis of Reading Ability), visual information processing tests (Coding and Symbol Search subtests from the Wechsler Intelligence Scale for Children) and a reading-related eye movement test (the Developmental Eye Movement test). Each participant was systematically assigned either with-the-rule (WTR, axis 180°) or against-the-rule (ATR, axis 90°) simulated astigmatism to evaluate the influence of axis orientation on any decrements in performance. Results: Reading, visual information processing and reading-related eye movement performance were all significantly impaired by both simulated bilateral astigmatism (p<0.001) and sustained near work (p<0.001), however, there was no significant interaction between these factors (p>0.05). Simulated astigmatism led to a reduction of between 5% and 12% in performance across the academic-related outcome measures, but there was no significant effect of the axis (WTR or ATR) of astigmatism (p>0.05). Conclusion: Simulated bilateral astigmatism impaired children’s performance on a range of academic–related outcome measures irrespective of the orientation of the astigmatism. These findings have implications for the clinical management of non-amblyogenic levels of astigmatism in relation to academic performance in children. Correction of low to moderate levels of astigmatism may improve the functional performance of children in the classroom.

Molecular Pathways of Disturbed Sleep and Depression: Studies on Adenosine and Gene Expression Patterns

Background: Adenosine is a potent sleep-promoting substance, and one of its targets is the basal forebrain. Fairly little is known about its mechanism of action in the basal forebrain and about the receptor subtype mediating its regulating effects on sleep homeostasis. Homeostatic deficiency might be one of the causes of the profoundly disturbed sleep pattern in major depressive disorder, which could explain the reduced amounts of delta-activity-rich stages 3 and 4. Since major depression has a relatively high heritability, and on the other hand adenosine regulates sleep homeostasis and might also be involved in mood modulation, adenosine-related genes should be considered for their possible contribution to a predisposition for depression and disturbed sleep in humans. Depression is a complex disorder likely involving the abnormal functioning of several genes. Novel target genes which could serve as the possible common substrates for depression and comorbid disturbed sleep should be identified. In this way specific brain areas related to sleep regulation should be studied by using animal model of depression which represents more homogenous phenotype as compared to humans. It is also important to study these brain areas during the development of depressive-like features to understand how early changes could facilitate pathophysiological changes in depression. Aims and methods: We aimed to find out whether, in the basal forebrain, adenosine induces recovery non-rapid eye movement (NREM) sleep after prolonged waking through the A1 or/and A2A receptor subtype. A1 and A2A receptor antagonists were perfused into the rat basal forebrain during 3 h of sleep deprivation, and the amount of NREM sleep and delta power during recovery NREM sleep were analyzed. We then explored whether polymorphisms in genes related to the metabolism, transport and signaling of adenosine could predispose to depression accompanied by signs of disturbed sleep. DNA from 1423 individuals representative of the Finnish population and including controls and cases with depression, depression accompanied by early morning awakenings and depression accompanied by fatigue, was used in the study to investigate the possible association between polymorphisms from adenosine-related genes and cases. Finally to find common molecular substrates of depression and disturbed sleep, gene expression changes were investigated in specific brain areas in the rat clomipramine model of depression. We focused on the basal forebrain of 3-week old clomipramine-treated rats which develop depressive-like symptoms later in adulthood and on the hypothalamus of adult female clomipramine-treated rats. Results: Blocking of the A1 receptor during sleep deprivation resulted in a reduction of the recovery NREM sleep amount and delta power, whereas A2A receptor antagonism had no effect. Polymorphisms in adenosine-related genes SLC29A3 (equilibrative nucleoside transporter type 3) in women and SLC28A1 (concentrative nucleoside transporter type 1) in men associated with depression alone as well as when accompanied by early morning awakenings and fatigue. In Study III the basal forebrain of postnatal rats treated with clomipramine displayed disturbances in gamma-aminobutyric acid (GABA) receptor type A signaling, in synaptic transmission and possible epigenetic changes. CREB1 was identified as a common transcription denominator which also mediates epigenetic regulation. In the hypothalamus the major changes included the expression of genes in GABA-A receptor pathway, K+ channel-related, glutamatergic and mitochondrial genes, as well as an overexpression of genes related to RNA and mRNA processing. Conclusions: Adenosine plays an important role in sleep homeostasis by promoting recovery NREM sleep via the A1 receptor subtype in the basal forebrain. Also adenosine levels might contribute to the risk of depression with disturbed sleep, since the genes encoding nucleoside transporters showed the strongest associations with depression alone and when accompanied by signs of disturbed sleep in both women and men. Sleep and mood abnormalities in major depressive disorder could be a consequence of multiple changes at the transcriptional level, GABA-A receptor signaling and synaptic transmission in sleep-related basal forebrain and the hypothalamus.

Effect of colostrum feeding method and presence of dam on the sleep, rest and sucking behaviour of newborn calves

"In rats, sucking milk reduces anxiety and promotes non-rapid eye movement (NREM) sleep, and in calves it induces resting but the effect on sleep is unknown. Here, we investigated how calves' sleep was affected by colostrum feeding methods. Forty-one calves were blocked by birth date and randomly allotted within blocks to the experimental treatments. Calves were housed for four days either with their dam (DAM) or individually with warm colostrum feeding (2 L four times a day) from either a teat bucket (TEAT) or an open bucket (BUCKET). DAM calves suckled their dam freely. Calves' sleeping and sucking behaviour was filmed continuously for 48 h at the ages of two and three days. Behavioural sleep (BS) was defined as calves resting at least 30 s with their head still and raised (non-rapid eye movement) or with their head against their body or the ground (rapid eye movement, REM). Latency from the end of colostrum feeding to the start of BS was recorded. We compared behaviour of TEAT calves with that of DAM and BUCKET calves using mixed models. Milk meal duration was significantly longer for TEAT calves than for BUCKET calves (mean +/- S.E.M.; 8.3 +/- 0.6 min vs. 5.2 +/- 0.6 min), but equal to that of DAM calves. We found no effect of feeding method on the duration of daily BS (12 h 59 min I h 38 min) but we found a tendency for the daily amount of NREM sleep; BUCKET calves had less NREM sleep per day than TEAT calves (6 h 18 min vs. 7 h 48 min, S.E.M. = 45 min) and also longer latencies from milk ingestion to BS (21.9 +/- 2.0 min vs. 16.2 +/- 2.0 min). DAM calves slept longer bouts than TEAT calves (10.8 +/- 1.0 min vs. 8.3 +/- 1.0 min) and less often (78 +/- 4 vs. 92 +/- 4). Sucking colostrum from a teat bucket compared with drinking from an open"

A mimetic-based frequency domain technique for automatic generation of EEG reports

This paper describes a novel mimetic technique of using frequency domain approach and digital filters for automatic generation of EEG reports. Digitized EEG data files, transported on a cartridge, have been used for the analysis. The signals are filtered for alpha, beta, theta and delta bands with digital bandpass filters of fourth-order, cascaded, Butterworth, infinite impulse response (IIR) type. The maximum amplitude, mean frequency, continuity index and degree of asymmetry have been computed for a given EEG frequency band. Finally, searches for the presence of artifacts (eye movement or muscle artifacts) in the EEG records have been made.

A study on fear memory retrieval and REM sleep in maternal separation and isolation stressed rats

As rapid brain development occurs during the neonatal period, environmental manipulation during this period may have a significant impact on sleep and memory functions. Moreover, rapid eye movement (REM) sleep plays an important role in integrating new information with the previously stored emotional experience. Hence, the impact of early maternal separation and isolation stress (MS) during the stress hyporesponsive period (SHRP) on fear memory retention and sleep in rats were studied. The neonatal rats were subjected to maternal separation and isolation stress during postnatal days 5-7 (6 h daily/3 d). Polysomnographic recordings and differential fear conditioning was carried out in two different sets of rats aged 2 months. The neuronal replay during REM sleep was analyzed using different parameters. MS rats showed increased time in REM stage and total sleep period also increased. MS rats showed fear generalization with increased fear memory retention than normal control (NC). The detailed analysis of the local field potentials across different time periods of REM sleep showed increased theta oscillations in the hippocampus, amygdala and cortical circuits. Our findings suggest that stress during SHRP has sensitized the hippocampus amygdala cortical loops which could be due to increased release of corticosterone that generally occurs during REM sleep. These rats when subjected to fear conditioning exhibit increased fear memory and increased, fear generalization. The development of helplessness, anxiety and sleep changes in human patients, thus, could be related to the reduced thermal, tactile and social stimulation during SHRP on brain plasticity and fear memory functions. (C) 2014 Elsevier B.V. All rights reserved.

Macaque lateral intraparietal area and oculomotor behaviors

Neurons in the primate lateral intraparietal area (area LIP) carry visual, saccade-related and eye position activities. The visual and saccade activities are anchored in a retinotopic framework and the overall response magnitude is modulated by eye position. It was proposed that the modulation by eye position might be the basis of a distributed coding of target locations in a head-centered space. Other recording studies demonstrated that area LIP is involved in oculomotor planning. These results overall suggest that area LIP transforms sensory information for motor functions. In this thesis I further explore the role of area LIP in processing saccadic eye movements by observing the effects of reversible inactivation of this area. Macaque monkeys were trained to do visually guided and memory saccades and a double saccade task to examine the use of eye position signal. Finally, by intermixing visual saccades with trials in which two targets were presented at opposite sides of the fixation point, I examined the behavior of visual extinction.

In chapter 2, I will show that lesion of area LIP results in increased latency of contralesional visual and memory saccades. Contralesional memory saccades are also hypometric and slower in velocity. Moreover, the impairment of memory saccades does not vary with the duration of the delay period. This suggests that the oculomotor deficits observed after inactivation of area LIP is not due to the disruption of spatial memory.

In chapter 3, I will show that lesion of area LIP does not severely affect the processing of spontaneous eye movement. However, the monkeys made fewer contralesional saccades and tended to confine their gaze to the ipsilesional field after inactivation of area LIP. On the other hand, lesion of area LIP results in extinction of the contralesional stimulus. When the initial fixation position was varied so that the retinal and spatial locations of the targets could be dissociated, it was found that the extinction behavior could best be described in a head-centered coordinate.

In chapter 4, I will show that inactivation of area LIP disrupts the use of eye position signal to compute the second movement correctly in the double saccade task. If the first saccade steps into the contralesional field, the error rate and latency of the second saccade are both increased. Furthermore, the direction of the first eye movement largely does not have any effect on the impairment of the second saccade. I will argue that this study provides important evidence that the extraretinal signal used for saccadic localization is eye position rather than a displacement vector.

In chapter 5, I will demonstrate that in parietal monkeys the eye drifts toward the lesion side at the end of the memory saccade in darkness. This result suggests that the eye position activity in the posterior parietal cortex is active in nature and subserves gaze holding.

Overall, these results further support the view that area LIP neurons encode spatial locations in a craniotopic framework and is involved in processing voluntary eye movements.

MEMS for Diabetic Retinopathy

As the worldwide prevalence of diabetes mellitus continues to increase, diabetic retinopathy remains the leading cause of visual impairment and blindness in many developed countries. Between 32 to 40 percent of about 246 million people with diabetes develop diabetic retinopathy. Approximately 4.1 million American adults 40 years and older are affected by diabetic retinopathy. This glucose-induced microvascular disease progressively damages the tiny blood vessels that nourish the retina, the light-sensitive tissue at the back of the eye, leading to retinal ischemia (i.e., inadequate blood flow), retinal hypoxia (i.e., oxygen deprivation), and retinal nerve cell degeneration or death. It is a most serious sight-threatening complication of diabetes, resulting in significant irreversible vision loss, and even total blindness.

Unfortunately, although current treatments of diabetic retinopathy (i.e., laser therapy, vitrectomy surgery and anti-VEGF therapy) can reduce vision loss, they only slow down but cannot stop the degradation of the retina. Patients require repeated treatment to protect their sight. The current treatments also have significant drawbacks. Laser therapy is focused on preserving the macula, the area of the retina that is responsible for sharp, clear, central vision, by sacrificing the peripheral retina since there is only limited oxygen supply. Therefore, laser therapy results in a constricted peripheral visual field, reduced color vision, delayed dark adaptation, and weakened night vision. Vitrectomy surgery increases the risk of neovascular glaucoma, another devastating ocular disease, characterized by the proliferation of fibrovascular tissue in the anterior chamber angle. Anti-VEGF agents have potential adverse effects, and currently there is insufficient evidence to recommend their routine use.

In this work, for the first time, a paradigm shift in the treatment of diabetic retinopathy is proposed: providing localized, supplemental oxygen to the ischemic tissue via an implantable MEMS device. The retinal architecture (e.g., thickness, cell densities, layered structure, etc.) of the rabbit eye exposed to ischemic hypoxic injuries was well preserved after targeted oxygen delivery to the hypoxic tissue, showing that the use of an external source of oxygen could improve the retinal oxygenation and prevent the progression of the ischemic cascade.

The proposed MEMS device transports oxygen from an oxygen-rich space to the oxygen-deficient vitreous, the gel-like fluid that fills the inside of the eye, and then to the ischemic retina. This oxygen transport process is purely passive and completely driven by the gradient of oxygen partial pressure (pO₂). Two types of devices were designed. For the first type, the oxygen-rich space is underneath the conjunctiva, a membrane covering the sclera (white part of the eye), beneath the eyelids and highly permeable to oxygen in the atmosphere when the eye is open. Therefore, sub-conjunctival pO₂ is very high during the daytime. For the second type, the oxygen-rich space is inside the device since pure oxygen is needle-injected into the device on a regular basis.

To prevent too fast or too slow permeation of oxygen through the device that is made of parylene and silicone (two widely used biocompatible polymers in medical devices), the material properties of the hybrid parylene/silicone were investigated, including mechanical behaviors, permeation rates, and adhesive forces. Then the thicknesses of parylene and silicone became important design parameters that were fine-tuned to reach the optimal oxygen permeation rate.

The passive MEMS oxygen transporter devices were designed, built, and tested in both bench-top artificial eye models and in-vitro porcine cadaver eyes. The 3D unsteady saccade-induced laminar flow of water inside the eye model was modeled by computational fluid dynamics to study the convective transport of oxygen inside the eye induced by saccade (rapid eye movement). The saccade-enhanced transport effect was also demonstrated experimentally. Acute in-vivo animal experiments were performed in rabbits and dogs to verify the surgical procedure and the device functionality. Various hypotheses were confirmed both experimentally and computationally, suggesting that both the two types of devices are very promising to cure diabetic retinopathy. The chronic implantation of devices in ischemic dog eyes is still underway.

The proposed MEMS oxygen transporter devices can be also applied to treat other ocular and systemic diseases accompanied by retinal ischemia, such as central retinal artery occlusion, carotid artery disease, and some form of glaucoma.