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.

Efeito da privação de sono paradoxal na expressão de receptores para glicocorticoides no hipocampo e no aprendizado e memória

Vários trabalhos têm demonstrado uma relação entre sono e memória. Desta forma, tem sido descrito um papel importante do sono na consolidação da memória e um efeito negativo pela privação do mesmo. O hipocampo é uma região importante para a formação e consolidação da memória espacial, e contém uma alta expressão de receptores para corticosteróides. As ações dos corticosteróides no hipocampo são fundamentais para a aquisição de memória e dependem de um balanço adequado entre receptores de Glicocorticóides (RGc) e Mineralocorticóides (RMn). Assim é descrito na literatura que um aumento na expressão de RMn é promotor de aquisição de memória, enquanto que um aumento na expressão de RGc produz um efeito negativo. Apesar dos níveis circulantes de glicocorticóides na privação de sono paradoxal (PSP), não serem responsáveis pelo enfraquecimento de memória, não existem dados sobre a expressão dos receptores para corticosteróides no hipocampo, após PSP. Neste trabalho tivemos como objetivo investigar a expressão de receptores de Glicocorticóides no hipocampo, bem como avaliar aprendizado e memória em ratos privados de sono paradoxal. Ratos Wistar machos (250- 350g) foram submetidos à PSP, utilizando-se o método de múltiplas plataformas por um período de 96 horas. Após 96h de privação os animais foram anestesiados e perfundidos. Secções de 25 μm na área do hipocampo foram obtidas e reagidas com anticorpos para receptores de Glicocortidóides. Avaliamos as áreas CA1, CA3 e Giro Denteado. O aprendizado e memória espacial foram avaliados através do teste do labirinto aquático de oito braços, antes e após o período de privação de sono. Avaliou-se a latência de escape e o número de erros obtidos. O grupo PSP apresentou um aumento na expressão de RGc nas regiões: CA1 e Giro Denteado, não se observando diferença significativa na região CA3. A PSP prévia aos testes de aprendizado e memória não provocou alterações significativas. A privação de sono pós-aprendizado também não produziu diferenças estatisticamente significativas, mas um aumento no tempo de latência de escape e número de erros sugere um enfraquecimento na consolidação da memória. O aumento na expressão de RGc nas áreas estudadas, pode ser consequente a uma alteração no balanço entre os receptores para corticosteróides no hipocampo e ser responsável por alterações no aprendizado e memória em ratos PSP.

序列学习场景条件下学习序列与空间记忆内在参照系的建立

Previous studies showed that preferred directions in pointing judgments (e.g. imagine you are standing at X, facing Y, please point to Z) were consistent with the sequence participants used to learn locations of objects suggesting that the learning sequence may determine the intrinsic frames of reference in spatial memory. Numerous studies pay excessive attention to the selection of intrinsic frames of reference in spatial memory acquired from viewing an entire layout simultaneously. This research focused on the relationship between the learning sequence and the spatial reference direction in sequentially learning a layout based on the theory of intrinsic reference system. The results indicated that: 1. The intrinsic frame of reference used to specify objects’ locations in memory could not be determined by learning sequence. The learning sequence reflected the encoding of interobject spatial relations aligned with the intrinsic reference directions . 2. when the objects presented sequentially in a random order and the layout geometry structure was either all along or briefly, the preferred heading was determined by the symmetric axis. when the objects presented sequentially in a random order and the layout geometry structure was either not indicated or briefly presented after study, the preferred heading was determined by learning viewpoint. 3. When the objects were presented sequentially along a certain direction, whether the layout geometry structure displayed or not, the effect of the learning viewpoint on selection of intrinsic axis was observed. 4. When participants learned a layout during locomotion, whether the layout geometry structure displayed or not, the initial study perspective was used as a reference direction in memory. 5. Spatial reference direction was determined at the very beginning of learning objects’ locations. Spatial reference direction could not be changed once it had been choosed. These results not only contribute to specify in greater detail the nature of these spatial representations but also extend the intrinsic model of spatial memory.

多视点学习条件下场景内在参照系的建立

The aim of the present study was to investigate whether people can establish two oblique spatial reference directions to represent objects’ locations in memory. Participants learned a layout of objects from two oblique viewpoints (0º and 225º) and made judgments of relative direction (“Imagine you are standing at X, facing Y, please point to Z”). Experiments 1 to 3 showed that performance in pointing were better at either one of the familiar imagined headings (0º and 225º) in most of the participants even when they were instructed to learn the layout along their actual heading at both learning directions, and when their actual headings at the test were the same as the imagined headings. Experiments 4 to 6 showed performance in pointing could be equivalent at the two familiar imagined headings for significant number of the participants when participants learned two different set of objects occupied at the same locations from the two learning viewpoints, and when participants learned the same layout of objects together with two different layouts from the two learning viewpoints. These results suggest that the orientation dependent performance in Experiments 1 to 3 cannot be attributed to the possibility that participants had formed two oblique spatial reference directions during learning but only used one of them during testing. Experiments 7 and 8 further showed that the performance of pointing at the two familiar viewpoints were significantly different when participants experienced one viewpoint by learning the actual layout and the other viewpoint by learning the map of the same layout, and when participants experienced two viewpoints alternatively over the ten times of learning sessions. All these results strongly suggest that people establish only one spatial reference system to represent locations of objects when they learn the same layout in the same background from two oblique viewpoints.

物体朝向对场景内在参照系建立的影响

Six experiments tested how headings of objects in scenes influenced the construction for the intrinsic frame of reference under different structure and viewpoint amount conditions. In Experiment 1 and 2, participants stood at 0 degree and learned an asymmetrical scene and a symmetrical scene that were composed by balls with no apparent headings separately. In Experiment 3, 4, 5 and 6, toys with apparent headings were used and they all faced the 315 degree of the scene. In Experiment 3 and 4, participants stood at 0 degree and learned an asymmetrical scene and a symmetrical scene that were composed by toys separately. In Experiment 5 and 6, participants stood at 0 and 315 degree and learned an asymmetrical scene and a symmetrical scene that were composed by toys separately. After learning, participants needed to finish triplet recognition tasks in all the experiments. The dependent measures were response latency and accuracy. The correct response latencies to the targets were analyzed by ANOVA. Accuracy was used to filter data and analyzed in an ANOVA in some experiments as a reference. Results indicate that headings of objects in scenes influence the pattern for intrinsic frame of reference. The structure of scene affects the acting mechanism of heading, but the amount of viewpoints does not have this effect. If the objects in scenes have no apparent headings, there will be viewpoint dependent effect and the advantage of symmetry axis as intrinsic axis in triplet recognition tasks. If the objects in scenes have apparent headings, people’s spatial memory pattern will be affected by objects’ headings. If the heading of objects (315 degree) is not parallel to the viewpoint (0 degree) in an asymmetrical scene, people will be inclined to represent the scene from the heading of objects but not from the viewpoint. As a result, the viewpoint dependent effect will disappear, and there is significant advantage for the triplets presented from heading of objects. If the heading of objects is not parallel to the symmetry axis in a symmetrical scene, people will represent the scene not only according to the symmetry axis as intrinsic axis, but also according to the heading of objects. As a result, the significant advantage for symmetry axis as intrinsic axis in triplet recognition tasks will disappear but there will be still a tendency. By contrast, the effect for the headings of objects is more significant in asymmetrical scenes than that in symmetrical scenes.

空间情境模型中以观察者为中心的空间关系表征

Human being built and updated the representations of spatial distances and spatial relations between protagonist and the around things in language comprehension. The representations of the spatial relations in egocentric spatial situational models were important in spatial cognition, narrative comprehension and psycholinguistic. Using imagery searching paradigm, Franklin and Tversky (1990) studied the representations of the spatial relations in egocentric spatial situational models and found the standard RT pattern of searching the objects in different directions around the observer (frontspatial relations in egocentric framework: Body-Object relation and Object-Object relation. Without relation position effect, the standard RT pattern was found in reacting to direction nouns in Experiment 4, whereas another RT pattern (left=right=frontspatial memory, the difficulty of retrieving objects in front, back, right or left is different(front=right=leftspatial representation, as consequence, front-back, right-left directions represents near than other pairs. So from front to back, from back to front, from right to left or from left to right, is quick than other pairs. With the 45-degree count-clockwise rotation of the objects around the body, the geometric distance between them determined the psychological distance between two objects. As a conclusion, the structural natures of the spatial representation determined the nature of spatial relations.

Neonatal exposure to estradiol in female rats influences neuroactive steroid concentrations and behaviour in the adult rat

The gonadal steroids, in particular estradiol, exert an important action during perinatal period in the regulation of sexual dimorphism and neuronal plasticity, and in the growth and development of nervous system. Exposure of the developing female to estrogens during perinatal period may have long-lasting effects that are now regarded as “programming” the female neuroendocrine axis to malfunction in adulthood. The purpose of this study was to describe the effect of a single administration of a low dose (10 μg) of β-estradiol 3-benzoate (EB) to female rats on the day of birth on brain and plasma concentrations of the neuroactive steroid allopregnanolone, general behaviours and behavioral sensitivity to benzodiazepines. Neonatal administration of EB induces a dramatic reduction in the cerebrocortical and plasma levels of allopregnanolone and progesterone that were apparent in both juvenile (21 days) and adult (60 days). In contrast, this treatment did not affect 17β-estradiol levels. Female rats treated with β-estradiol 3-benzoate showed a delay in vaginal opening, aciclicity characterized by prolonged estrus, and ovarian failure. Given that allopregnanolone elicits anxiolytic, antidepressive, anticonvulsant, sedative-hypnotic effects and facilitates social behaviour, we assessed whether this treatment might modify different emotional, cognitive and social behaviours. This treatment did not affect locomotor activity, anxiety- and mood-related behaviours, seizures sensitivity and spatial memory. In contrast, neonatal β-estradiol 3-benzoate-treated rats showed a dominant, but not aggressive, behaviour and an increase in body investigation, especially anogenital investigation, characteristic of male appetitive behaviour. On the contrary, neonatal administration of β-estradiol 3-benzoate to female rats increases sensitivity to the anxiolytic, sedative, and amnesic effects of diazepam in adulthood. These results indicate that the marked and persistent reduction in the cerebrocortical and peripheral concentration of the neuroactive steroid allopregnanolone induced by neonatal treatment with β-estradiol 3-benzoate does not change baseline behaviours in adult rats. On the contrary, the low levels of allopregnanolone seems to be associated to changes in the behavioural sensitivity to the positive allosteric modulator of the GABAA receptor, diazepam. These effects of estradiol suggest that it plays a major role in pharmacological regulation both of GABAergic transmission and of the abundance of endogenous modulators of such transmission during development of the central nervous system.

Emergent group level navigation: an agent-based evaluation of movement patterns in a folivorous primate.

The foraging activity of many organisms reveal strategic movement patterns, showing efficient use of spatially distributed resources. The underlying mechanisms behind these movement patterns, such as the use of spatial memory, are topics of considerable debate. To augment existing evidence of spatial memory use in primates, we generated movement patterns from simulated primate agents with simple sensory and behavioral capabilities. We developed agents representing various hypotheses of memory use, and compared the movement patterns of simulated groups to those of an observed group of red colobus monkeys (Procolobus rufomitratus), testing for: the effects of memory type (Euclidian or landmark based), amount of memory retention, and the effects of social rules in making foraging choices at the scale of the group (independent or leader led). Our results indicate that red colobus movement patterns fit best with simulated groups that have landmark based memory and a follow the leader foraging strategy. Comparisons between simulated agents revealed that social rules had the greatest impact on a group's step length, whereas the type of memory had the highest impact on a group's path tortuosity and cohesion. Using simulation studies as experimental trials to test theories of spatial memory use allows the development of insight into the behavioral mechanisms behind animal movement, developing case-specific results, as well as general results informing how changes to perception and behavior influence movement patterns.

Brain activity during episodic retrieval of autobiographical and laboratory events: an fMRI study using a novel photo paradigm.

Functional neuroimaging studies of episodic memory retrieval generally measure brain activity while participants remember items encountered in the laboratory ("controlled laboratory condition") or events from their own life ("open autobiographical condition"). Differences in activation between these conditions may reflect differences in retrieval processes, memory remoteness, emotional content, retrieval success, self-referential processing, visual/spatial memory, and recollection. To clarify the nature of these differences, a functional MRI study was conducted using a novel "photo paradigm," which allows greater control over the autobiographical condition, including a measure of retrieval accuracy. Undergraduate students took photos in specified campus locations ("controlled autobiographical condition"), viewed in the laboratory similar photos taken by other participants (controlled laboratory condition), and were then scanned while recognizing the two kinds of photos. Both conditions activated a common episodic memory network that included medial temporal and prefrontal regions. Compared with the controlled laboratory condition, the controlled autobiographical condition elicited greater activity in regions associated with self-referential processing (medial prefrontal cortex), visual/spatial memory (visual and parahippocampal regions), and recollection (hippocampus). The photo paradigm provides a way of investigating the functional neuroanatomy of real-life episodic memory under rigorous experimental control.

Investigation of the effect of intrauterine inflammation and infection on fetal brain injury using human and animal models

In recent years, increased focus has been placed on the role of intrauterine infection and inflammation in the pathogenesis of fetal brain injury leading to neurodevelopmental disorders such as cerebral palsy. At present, the mechanisms by which inflammatory processes during pregnancy cause this effect on the fetus are poorly understood. Our previous work has indicated an association between experimentally-induced intrauterine infection, increased proinflammatory cytokines, and increased white matter injury in the guinea pig fetus. In order to further elucidate the pathways by which inflammation in the maternal system or the fetal membranes leads to fetal impairment, a number of studies investigating aspects of the disease process have been performed. These studies represent a body of work encompassing novel research and results in a number of human and animal studies. Using a guinea pig model of inflammation, increased amniotic fluid proinflammatory cytokines and fetal brain injury were found after a maternal inflammatory response was initiated using endotoxin. In order to more closely monitor the fetal response to chorioamnionitis, a model using the chronically catheterized fetal ovine was carried out. This study demonstrated the adverse effects on fetal white matter after intrauterine exposure to bacterial inoculation, though the physiological parameters of the fetus were relatively stable throughout the experimental protocol, even when challenged with intermittent hypoxic episodes. The placenta is an important mediator between mother and fetus during gestation, though its role in the inflammatory process is largely undefined. Studies on the placental role in the inflammatory process were undertaken, and the limited ability of proinflammatory cytokines and endotoxin to cross the placenta are detailed herein. Neurodevelopmental disorders can be monitored in animal models in order to determine effective disease models for characterization of injury and use in therapeutic strategies. Our characterizations of postnatal behaviour in the guinea pig model using motility monitoring and spatial memory testing have shown small but significant differences in pups exposed to inflammatory processes in utero. The data presented herein contributes a breadth of knowledge to the ongoing elucidation of the pathways by which fetal brain injury occurs. Determining the pathway of damage will lead to discovery of diagnostic criteria, while determining the vulnerabilities of the developing fetus is essential in formulating therapeutic options.

Fos imaging reveals that lesions of the anterior thalamic nuclei produce widespread limbic hypoactivity in rats

Activity of the immediate early gene c-fos was compared in rats with neurotoxic lesions of the anterior thalamic nuclei and in surgical controls. Fos levels were measured after rats had been placed in a novel room and allowed to run up and down preselected arms of a radial maze. An additional control group showed that in normal rats, this exposure to a novel room leads to a Fos increase in a number of structures, including the anterior thalamic nuclei and hippocampus. In contrast, rats with anterior thalamic lesions were found to have significantly less Fos-positive cells in an array of sites, including the hippocampus (dorsal and ventral), retrosplenial cortex, anterior cingulate cortex, and prelimbic cortex. These results show that anterior thalamic lesions disrupt multiple limbic brain regions, producing hypoactivity in sites associated in rats with spatial memory. Because many of the same sites are implicated in memory processes in humans (e.g., the hippocampus and retrosplenial cortex), this hypoactivity might contribute to diencephalic amnesia.

Donepezil attenuates hippocampal neuronal damage and cognitive deficits after global cerebral ischemia in gerbils.

Decreased cerebral blood flow causes cognitive impairments and neuronal injury in vascular dementia. In the present study, we reported that donepezil, a cholinesterase inhibitor, improved transient global cerebral ischemia-induced spatial memory impairment in gerbils. Treatment with 5mg/kg of donepezil for 21 consecutive days following a 10-min period of ischemia significantly inhibited delayed neuronal death in the hippocampal CA1 region. In Morris water maze test, memory impairment was significantly improved by donepezil treatment. Western blot analysis showed that donepezil treatment prevented reductions in p-CaMKII and p-CREB protein levels in the hippocampus. These results suggest that donepezil attenuates the memory deficit induced by transient global cerebral ischemia and this neuroprotection may be associated with the phosphorylation of CaMKII and CERB in the hippocampus.

Magnetoencephalography study of brain dynamics in young children born extremely preterm

Magnetoencephalography (MEG) was recorded while 5-7 year-old children were performing a visual-spatial memory recognition task. Full-term children showed greater gamma-band (30-50 Hz) amplitude in the right temporal region during the task, than children who were born extremely preterm. These results may represent altered brain processing in extremely preterm children who escape major impairment.

Do challenge, task experience or computer familiarity influence the learning of historical chronology from virtual environments in 8–9 year old children?

Studies examined the potential use of Virtual Environments (VEs) in teaching historical chronology to 127 children of primary school age (8–9 years). The use of passive fly-through VEs had been found, in an earlier study, to be disadvantageous with this age group when tested for their subsequent ability to place displayed sequential events in correct chronological order. All VEs in the present studies included active challenge, previously shown to enhance learning in older participants. Primary school children in the UK (all frequent computer users) were tested using UK historical materials, but no significant effect was found between three conditions (Paper, PowerPoint and VE) with minimal pre-training. However, excellent (error free) learning occurred when children were allowed greater exploration prior to training in the VE. In Ukraine, with children having much less computer familiarity, training in a VE (depicting Ukrainian history) produced better learning compared to PowerPoint, but no better than in a Paper condition. The results confirmed the benefit of using challenge in a VE with primary age children, but only with adequate prior familiarisation with the medium. Familiarity may reduce working memory load and increase children’s spatial memory capacity for acquiring sequential temporal-spatial information from virtual displays. Keywords: timeline, chronographics