The effect of overweight/obesity on cognitive function in euthymic individuals with bipolar disorder

Background. - Persistent impairment in cognitive function has been described in euthymic individuals with bipolar disorder. Collective work indicates that obesity is associated with reduced cognitive function in otherwise healthy individuals. This sub-group post-hoc analysis preliminarily explores and examines the association between overweight/obesity and cognitive function in euthymic individuals with bipolar disorder. Methods. - Euthymic adults with DSM-IV-TR-defined bipolar I or II disorder were enrolled. Subjects included in this post-hoc analysis (n = 67) were divided into two groups (normal weight, body mass index [BMI] of 18.5-24.9 kg/m(2); overweight/obese, BMI >= 25.0 kg/m(2)). Demographic and clinical information were obtained at screening. At baseline, study participants completed a comprehensive cognitive battery to assess premorbid IQ, verbal learning and memory, attention and psychomotor processing speed, executive function, general intellectual abilities, recollection and habit memory, as well as self-perceptions of cognitive failures. Results. - BMI was negatively correlated with attention and psychomotor processing speed as measured by the Digit Symbol Substitution Test (P < 0.01). Overweight and obese bipolar individuals had a significantly lower score on the Verbal Fluency Test when compared to normal weight subjects (P < 0.05). For all other measures of cognitive function, non-significant trends suggesting a negative association with BMI were observed, with the exception of measures of executive function (i.e. Trail Making Test B) and recollection memory (i.e. process-dissociation task). Conclusion. - Notwithstanding the post-hoc methodology and relatively small sample size, the results of this study suggest a possible negative effect of overweight/obesity on cognitive function in euthymic individuals with bipolar disorder. Taken together, these data provide the impetus for more rigorous evaluation of the mediational role of overweight/obesity (and other medical co-morbidity) on cognitive function in psychiatric populations. (C) 2011 Elsevier Masson SAS. All rights reserved.

Motor learning, retention and transfer after virtual-reality-based training in Parkinson's disease - effect of motor and cognitive demands of games: a longitudinal, controlled clinical study

Objectives To evaluate the learning, retention and transfer of performance improvements after Nintendo Wii Fit (TM) training in patients with Parkinson's disease and healthy elderly people. Design Longitudinal, controlled clinical study. Participants Sixteen patients with early-stage Parkinson's disease and 11 healthy elderly people. Interventions Warm-up exercises and Wii Fit training that involved training motor (shifts centre of gravity and step alternation) and cognitive skills. A follow-up evaluative Wii Fit session was held 60 days after the end of training. Participants performed a functional reach test before and after training as a measure of learning transfer. Main outcome measures Learning and retention were determined based on the scores of 10 Wii Fit games over eight sessions. Transfer of learning was assessed after training using the functional reach test. Results Patients with Parkinson's disease showed no deficit in learning or retention on seven of the 10 games, despite showing poorer performance on five games compared with the healthy elderly group. Patients with Parkinson's disease showed marked learning deficits on three other games, independent of poorer initial performance. This deficit appears to be associated with cognitive demands of the games which require decision-making, response inhibition, divided attention and working memory. Finally, patients with Parkinson's disease were able to transfer motor ability trained on the games to a similar untrained task. Conclusions The ability of patients with Parkinson's disease to learn, retain and transfer performance improvements after training on the Nintendo Wii Fit depends largely on the demands, particularly cognitive demands, of the games involved, reiterating the importance of game selection for rehabilitation purposes. (C) 2012 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Disruption of vitellogenin gene function in adult honeybees by intra-abdominal injection of double-stranded RNA

Abstract Background The ability to manipulate the genetic networks underlying the physiological and behavioural repertoires of the adult honeybee worker (Apis mellifera) is likely to deepen our understanding of issues such as learning and memory generation, ageing, and the regulatory anatomy of social systems in proximate as well as evolutionary terms. Here we assess two methods for probing gene function by RNA interference (RNAi) in adult honeybees. Results The vitellogenin gene was chosen as target because its expression is unlikely to have a phenotypic effect until the adult stage in bees. This allowed us to introduce dsRNA in preblastoderm eggs without affecting gene function during development. Of workers reared from eggs injected with dsRNA derived from a 504 bp stretch of the vitellogenin coding sequence, 15% had strongly reduced levels of vitellogenin mRNA. When dsRNA was introduced by intra-abdominal injection in newly emerged bees, almost all individuals (96 %) showed the mutant phenotype. An RNA-fragment with an apparent size similar to the template dsRNA was still present in this group after 15 days. Conclusion Injection of dsRNA in eggs at the preblastoderm stage seems to allow disruption of gene function in all developmental stages. To dissect gene function in the adult stage, the intra-abdominal injection technique seems superior to egg injection as it gives a much higher penetrance, it is much simpler, and it makes it possible to address genes that are also expressed in the embryonic, larval or pupal stages.

Aktionenlernen mit Selbstorganisierenden Karten und Reinforcement Learning

Die vorliegende Arbeit beschäftigt sich mit der Entwicklung eines Funktionsapproximators und dessen Verwendung in Verfahren zum Lernen von diskreten und kontinuierlichen Aktionen: 1. Ein allgemeiner Funktionsapproximator – Locally Weighted Interpolating Growing Neural Gas (LWIGNG) – wird auf Basis eines Wachsenden Neuralen Gases (GNG) entwickelt. Die topologische Nachbarschaft in der Neuronenstruktur wird verwendet, um zwischen benachbarten Neuronen zu interpolieren und durch lokale Gewichtung die Approximation zu berechnen. Die Leistungsfähigkeit des Ansatzes, insbesondere in Hinsicht auf sich verändernde Zielfunktionen und sich verändernde Eingabeverteilungen, wird in verschiedenen Experimenten unter Beweis gestellt. 2. Zum Lernen diskreter Aktionen wird das LWIGNG-Verfahren mit Q-Learning zur Q-LWIGNG-Methode verbunden. Dafür muss der zugrunde liegende GNG-Algorithmus abgeändert werden, da die Eingabedaten beim Aktionenlernen eine bestimmte Reihenfolge haben. Q-LWIGNG erzielt sehr gute Ergebnisse beim Stabbalance- und beim Mountain-Car-Problem und gute Ergebnisse beim Acrobot-Problem. 3. Zum Lernen kontinuierlicher Aktionen wird ein REINFORCE-Algorithmus mit LWIGNG zur ReinforceGNG-Methode verbunden. Dabei wird eine Actor-Critic-Architektur eingesetzt, um aus zeitverzögerten Belohnungen zu lernen. LWIGNG approximiert sowohl die Zustands-Wertefunktion als auch die Politik, die in Form von situationsabhängigen Parametern einer Normalverteilung repräsentiert wird. ReinforceGNG wird erfolgreich zum Lernen von Bewegungen für einen simulierten 2-rädrigen Roboter eingesetzt, der einen rollenden Ball unter bestimmten Bedingungen abfangen soll.

Dopamine-related deficit in reward learning after catecholamine depletion in unmedicated, remitted subjects with bulimia nervosa

Disturbances in reward processing have been implicated in bulimia nervosa (BN). Abnormalities in processing reward-related stimuli might be linked to dysfunctions of the catecholaminergic neurotransmitter system, but findings have been inconclusive. A powerful way to investigate the relationship between catecholaminergic function and behavior is to examine behavioral changes in response to experimental catecholamine depletion (CD). The purpose of this study was to uncover putative catecholaminergic dysfunction in remitted subjects with BN who performed a reinforcement-learning task after CD. CD was achieved by oral alpha-methyl-para-tyrosine (AMPT) in 19 unmedicated female subjects with remitted BN (rBN) and 28 demographically matched healthy female controls (HC). Sham depletion administered identical capsules containing diphenhydramine. The study design consisted of a randomized, double-blind, placebo-controlled crossover, single-site experimental trial. The main outcome measures were reward learning in a probabilistic reward task analyzed using signal-detection theory. Secondary outcome measures included self-report assessments, including the Eating Disorder Examination-Questionnaire. Relative to healthy controls, rBN subjects were characterized by blunted reward learning in the AMPT-but not in placebo-condition. Highlighting the specificity of these findings, groups did not differ in their ability to perceptually distinguish between stimuli. Increased CD-induced anhedonic (but not eating disorder) symptoms were associated with a reduced response bias toward a more frequently rewarded stimulus. In conclusion, under CD, rBN subjects showed reduced reward learning compared with healthy control subjects. These deficits uncover disturbance of the central reward processing systems in rBN related to altered brain catecholamine levels, which might reflect a trait-like deficit increasing vulnerability to BN.

The free radical scavenger alpha-phenyl-tert-butyl nitrone aggravates hippocampal apoptosis and learning deficits in experimental pneumococcal meningitis

The effect of adjuvant therapy with the radical scavenger alpha-phenyl-tert-butyl nitrone (PBN; 100 mg/kg given intraperitoneally every 8 h for 5 days) on brain injury and learning function was evaluated in an infant rat model of pneumococcal meningitis. Meningitis led to cortical necrotic injury (median, 3.97% [range, 0%-38.9%] of the cortex), which was reduced to a median of 0% (range, 0%-30.9%) of the cortex (P<.001) by PBN. However, neuronal apoptosis in the hippocampal dentate gyrus was increased by PBN, compared with that by saline (median score, 1.15 [range, 0.04-1.73] vs. 0.31 [range, 0-0.92]; P<.001). Learning function 3 weeks after cured infection, as assessed by the Morris water maze, was decreased, compared with that in uninfected control animals (P<.001). Parallel to the increase in hippocampal apoptosis, PBN further impaired learning in infected animals, compared with that in saline-treated animals (P<.02). These results contrast with those of an earlier study, in which PBN reduced cortical and hippocampal neuronal injury in group B streptococcal meningitis. Thus, in pneumococcal meningitis, antioxidant therapy with PBN aggravates hippocampal injury and learning deficits.

Radiation metabolomics. 3. Biomarker discovery in the urine of gamma-irradiated rats using a simplified metabolomics protocol of gas chromatography-mass spectrometry combined with random forests machine learning algorithm

Abstract Radiation metabolomics employing mass spectral technologies represents a plausible means of high-throughput minimally invasive radiation biodosimetry. A simplified metabolomics protocol is described that employs ubiquitous gas chromatography-mass spectrometry and open source software including random forests machine learning algorithm to uncover latent biomarkers of 3 Gy gamma radiation in rats. Urine was collected from six male Wistar rats and six sham-irradiated controls for 7 days, 4 prior to irradiation and 3 after irradiation. Water and food consumption, urine volume, body weight, and sodium, potassium, calcium, chloride, phosphate and urea excretion showed major effects from exposure to gamma radiation. The metabolomics protocol uncovered several urinary metabolites that were significantly up-regulated (glyoxylate, threonate, thymine, uracil, p-cresol) and down-regulated (citrate, 2-oxoglutarate, adipate, pimelate, suberate, azelaate) as a result of radiation exposure. Thymine and uracil were shown to derive largely from thymidine and 2'-deoxyuridine, which are known radiation biomarkers in the mouse. The radiation metabolomic phenotype in rats appeared to derive from oxidative stress and effects on kidney function. Gas chromatography-mass spectrometry is a promising platform on which to develop the field of radiation metabolomics further and to assist in the design of instrumentation for use in detecting biological consequences of environmental radiation release.

Learning through life

Web 2.0 und soziale Netzwerke gaben erste Impulse für neue Formen der Online-Lehre, welche die umfassende Vernetzung von Objekten und Nutzern im Internet nachhaltig einsetzen. Die Vielfältigkeit der unterschiedlichen Systeme erschwert aber deren ganzheitliche Nutzung in einem umfassenden Lernszenario, das den Anforderungen der modernen Informationsgesellschaft genügt. In diesem Beitrag wird eine auf dem Konnektivismus basierende Plattform für die Online-Lehre namens “Wiki-Learnia” präsentiert, welche alle wesentlichen Abschnitte des lebenslangen Lernens abbildet. Unter Einsatz zeitgemäßer Technologien werden nicht nur Nutzer untereinander verbunden, sondern auch Nutzer mit dedizierten Inhalten sowie ggf. zugehörigen Autoren und/oder Tutoren verknüpft. Für ersteres werden verschiedene Kommunikations-Werkzeuge des Web 2.0 (soziale Netzwerke, Chats, Foren etc.) eingesetzt. Letzteres fußt auf dem sogenannten “Learning-Hub”-Ansatz, welcher mit Hilfe von Web-3.0-Mechanismen insbesondere durch eine semantische Metasuchmaschine instrumentiert wird. Zum Aufzeigen der praktischen Relevanz des Ansatzes wird das mediengestützte Juniorstudium der Universität Rostock vorgestellt, ein Projekt, das Schüler der Abiturstufe aufs Studium vorbereitet. Anhand der speziellen Anforderungen dieses Vorhabens werden der enorme Funktionsumfang und die große Flexibilität von Wiki-Learnia demonstriert.

More than synaptic plasticity: role of nonsynaptic plasticity in learning and memory.

Decades of research on the cellular mechanisms of memory have led to the widely held view that memories are stored as modifications of synaptic strength. These changes involve presynaptic processes, such as direct modulation of the release machinery, or postsynaptic processes, such as modulation of receptor properties. Parallel studies have revealed that memories might also be stored by nonsynaptic processes, such as modulation of voltage-dependent membrane conductances, which are expressed as changes in neuronal excitability. Although in some cases nonsynaptic changes can function as part of the engram itself, they might also serve as mechanisms through which a neural circuit is set to a permissive state to facilitate synaptic modifications that are necessary for memory storage.

Sulforaphane improves cognitive function administered following traumatic brain injury.

Recent studies have shown that sulforaphane, a naturally occurring compound that is found in cruciferous vegetables, offers cellular protection in several models of brain injury. When administered following traumatic brain injury (TBI), sulforaphane has been demonstrated to attenuate blood-brain barrier permeability and reduce cerebral edema. These beneficial effects of sulforaphane have been shown to involve induction of a group of cytoprotective, Nrf2-driven genes, whose protein products include free radical scavenging and detoxifying enzymes. However, the influence of sulforaphane on post-injury cognitive deficits has not been examined. In this study, we examined if sulforaphane, when administered following cortical impact injury, can improve the performance of rats tested in hippocampal- and prefrontal cortex-dependent tasks. Our results indicate that sulforaphane treatment improves performance in the Morris water maze task (as indicated by decreased latencies during learning and platform localization during a probe trial) and reduces working memory dysfunction (tested using the delayed match-to-place task). These behavioral improvements were only observed when the treatment was initiated 1h, but not 6h, post-injury. These studies support the use of sulforaphane in the treatment of TBI, and extend the previously observed protective effects to include enhanced cognition.

Mechanisms of perceptual learning of depth discrimination in random dot stereograms.

Perceptual learning is a training induced improvement in performance. Mechanisms underlying the perceptual learning of depth discrimination in dynamic random dot stereograms were examined by assessing stereothresholds as a function of decorrelation. The inflection point of the decorrelation function was defined as the level of decorrelation corresponding to 1.4 times the threshold when decorrelation is 0%. In general, stereothresholds increased with increasing decorrelation. Following training, stereothresholds and standard errors of measurement decreased systematically for all tested decorrelation values. Post training decorrelation functions were reduced by a multiplicative constant (approximately 5), exhibiting changes in stereothresholds without changes in the inflection points. Disparity energy model simulations indicate that a post-training reduction in neuronal noise can sufficiently account for the perceptual learning effects. In two subjects, learning effects were retained over a period of six months, which may have application for training stereo deficient subjects.

Cerebellar mechanisms for motor learning: Testing predictions from a large-scale computer simulation

The cerebellum is the major brain structure that contributes to our ability to improve movements through learning and experience. We have combined computer simulations with behavioral and lesion studies to investigate how modification of synaptic strength at two different sites within the cerebellum contributes to a simple form of motor learning—Pavlovian conditioning of the eyelid response. These studies are based on the wealth of knowledge about the intrinsic circuitry and physiology of the cerebellum and the straightforward manner in which this circuitry is engaged during eyelid conditioning. Thus, our simulations are constrained by the well-characterized synaptic organization of the cerebellum and further, the activity of cerebellar inputs during simulated eyelid conditioning is based on existing recording data. These simulations have allowed us to make two important predictions regarding the mechanisms underlying cerebellar function, which we have tested and confirmed with behavioral studies. The first prediction describes the mechanisms by which one of the sites of synaptic modification, the granule to Purkinje cell synapses (gr → Pkj) of the cerebellar cortex, could generate two time-dependent properties of eyelid conditioning—response timing and the ISI function. An empirical test of this prediction using small, electrolytic lesions of the cerebellar cortex revealed the pattern of results predicted by the simulations. The second prediction made by the simulations is that modification of synaptic strength at the other site of plasticity, the mossy fiber to deep nuclei synapses (mf → nuc), is under the control of Purkinje cell activity. The analysis predicts that this property should confer mf → nuc synapses with resistance to extinction. Thus, while extinction processes erase plasticity at the first site, residual plasticity at mf → nuc synapses remains. The residual plasticity at the mf → nuc site confers the cerebellum with the capability for rapid relearning long after the learned behavior has been extinguished. We confirmed this prediction using a lesion technique that reversibly disconnected the cerebellar cortex at various stages during extinction and reacquisition of eyelid responses. The results of these studies represent significant progress toward a complete understanding of how the cerebellum contributes to motor learning. ^

Learning -dependent plasticity of movement representations in the primate primary motor cortex

Primary motor cortex (M1) is involved in the production of voluntary movement and contains a complete functional representation, or map, of the skeletal musculature. This functional map can be altered by pathological experiences, such as peripheral nerve injury or stroke, by pharmacological manipulation, and by behavioral experience. The process by which experience-dependent alterations of cortical function occur is termed plasticity. In this thesis, plasticity of M1 functional organization as a consequence of behavioral experience was examined in adult primates (squirrel monkeys). Maps of movement representations were derived under anesthesia using intracortical microstimulation, whereby a microelectrode was inserted into the cortex to electrically stimulate corticospinal neurons at low current levels and evoke movements of the forelimb, principally of the hand. Movement representations were examined before and at several times after training on behavioral tasks that emphasized use of the fingers. Two behavioral tasks were utilized that dissociated the repetition of motor activity from the acquisition of motor skills. One task was easy to perform, and as such promoted repetitive motor activity without learning. The other task was more difficult, requiring the acquisition of motor skills for successful performance. Kinematic analysis indicated that monkeys used a consistent set of forelimb movements during pellet extractions. Functional mapping revealed that repetitive motor activity during the easier task did not produce plastic changes in movement representations. Instead, map plasticity, in the form of selective expansions of task-related movement representations, was only produced following skill acquisition on the difficult task. Additional studies revealed that, in general, map plasticity persisted without further training for up to three months, in parallel with the retention of task-related motor skills. Also, extensive additional training on the small well task produced further improvements in performance, and further changes in movement maps. In sum, these experiments support the following three conclusions regarding the role of M1 in motor learning. First, behaviorally-driven plasticity is learning-dependent, not activity-dependent. Second, plastic changes in M1 functional representations represent a neural correlate of acquired motor skills. Third, the persistence of map plasticity suggests that M1 is part of the neural substrate for the memory of motor skills. ^

Impaired learning of predators and lower prey survival under elevated CO2: a consequence of neurotransmitter interference

Ocean acidification is one of the most pressing environmental concerns of our time, and not surprisingly, we have seen a recent explosion of research into the physiological impacts and ecological consequences of changes in ocean chemistry. We are gaining considerable insights from this work, but further advances require greater integration across disciplines. Here, we showed that projected near-future CO2 levels impaired the ability of damselfish to learn the identity of predators. These effects stem from impaired neurotransmitter function; impaired learning under elevated CO2 was reversed when fish were treated with gabazine, an antagonist of the GABA-A receptor - a major inhibitory neurotransmitter receptor in the brain of vertebrates. The effects of CO2 on learning and the link to neurotransmitter interference were manifested as major differences in survival for fish released into the wild. Lower survival under elevated CO2 , as a result of impaired learning, could have a major influence on population recruitment.

Response threshold models, stochastic learning automata and ant colony optimization-based decentralized self-coordination algorithms for heterogeneous multi-tasks distribution in multi-robot systems

In recent decades, there has been an increasing interest in systems comprised of several autonomous mobile robots, and as a result, there has been a substantial amount of development in the eld of Articial Intelligence, especially in Robotics. There are several studies in the literature by some researchers from the scientic community that focus on the creation of intelligent machines and devices capable to imitate the functions and movements of living beings. Multi-Robot Systems (MRS) can often deal with tasks that are dicult, if not impossible, to be accomplished by a single robot. In the context of MRS, one of the main challenges is the need to control, coordinate and synchronize the operation of multiple robots to perform a specic task. This requires the development of new strategies and methods which allow us to obtain the desired system behavior in a formal and concise way. This PhD thesis aims to study the coordination of multi-robot systems, in particular, addresses the problem of the distribution of heterogeneous multi-tasks. The main interest in these systems is to understand how from simple rules inspired by the division of labor in social insects, a group of robots can perform tasks in an organized and coordinated way. We are mainly interested on truly distributed or decentralized solutions in which the robots themselves, autonomously and in an individual manner, select a particular task so that all tasks are optimally distributed. In general, to perform the multi-tasks distribution among a team of robots, they have to synchronize their actions and exchange information. Under this approach we can speak of multi-tasks selection instead of multi-tasks assignment, which means, that the agents or robots select the tasks instead of being assigned a task by a central controller. The key element in these algorithms is the estimation ix of the stimuli and the adaptive update of the thresholds. This means that each robot performs this estimate locally depending on the load or the number of pending tasks to be performed. In addition, it is very interesting the evaluation of the results in function in each approach, comparing the results obtained by the introducing noise in the number of pending loads, with the purpose of simulate the robot's error in estimating the real number of pending tasks. The main contribution of this thesis can be found in the approach based on self-organization and division of labor in social insects. An experimental scenario for the coordination problem among multiple robots, the robustness of the approaches and the generation of dynamic tasks have been presented and discussed. The particular issues studied are: Threshold models: It presents the experiments conducted to test the response threshold model with the objective to analyze the system performance index, for the problem of the distribution of heterogeneous multitasks in multi-robot systems; also has been introduced additive noise in the number of pending loads and has been generated dynamic tasks over time. Learning automata methods: It describes the experiments to test the learning automata-based probabilistic algorithms. The approach was tested to evaluate the system performance index with additive noise and with dynamic tasks generation for the same problem of the distribution of heterogeneous multi-tasks in multi-robot systems. Ant colony optimization: The goal of the experiments presented is to test the ant colony optimization-based deterministic algorithms, to achieve the distribution of heterogeneous multi-tasks in multi-robot systems. In the experiments performed, the system performance index is evaluated by introducing additive noise and dynamic tasks generation over time.