Binding Studies of Neuronal Nicotinic Acetylcholine Receptors Expressing Unnatural Amino Acids

Nicotinic acetylcholine receptors are pentameric ligand-gated ion channels mediating fast synaptic transmission throughout the peripheral and central nervous systems. They have been implicated in various processes related to cognitive functions, learning and memory, arousal, reward, motor control and analgesia. Therefore, these receptors present alluring potential therapeutic targets for the treatment of pain, epilepsy, Alzheimer’s disease, Parkinson’s disease, Tourette’s syndrome, schizophrenia, anxiety, depression and nicotine addiction. The work detailed in this thesis focuses on binding studies of neuronal nicotinic receptors and aims to further our knowledge of subtype specific functional and structural information.

Chapter 1 is an introductory chapter describing the structure and function of nicotinic acetylcholine receptors as well as the methodologies used for the dissertation work described herein. There are several different subtypes of nicotinic acetylcholine receptors known to date and the subtle variations in their structure and function present a challenging area of study. The work presented in this thesis deals specifically with the α4β2 subtype of nicotinic acetylcholine receptor. This subtype assembles into 2 closely related stoichiometries, termed throughout this thesis as A3B2 and A2B3 after their respective subunit composition. Chapter 2 describes binding studies of select nicotinic agonists on A3B2 and A2B3 receptors determined by whole-cell recording. Three key binding interactions, a cation-π and two hydrogen bonds, were probed for four nicotinic agonists, acetylcholine, nicotine, smoking cessation drug varenicline (Chantix®) and the related natural product cytisine.

Results from the binding studies presented in Chapter 2 show that the major difference in binding of these four agonists to A3B2 and A2B3 receptors lies in one of the two hydrogen bond interactions where the agonist acts as the hydrogen bond acceptor and the backbone NH of a conserved leucine residue in the receptor acts as the hydrogen bond donor. Chapter 3 focuses on studying the effect of modulating the hydrogen bond acceptor ability of nicotine and epibatidine on A3B2 receptor function determined by whole-cell recording. Finally, Chapter 4 describes single-channel recording studies of varenicline binding to A2B3 and A3B2 receptors.

A biologia moral da atenção: a constituição do sujeito (des)atento

Esse trabalho analisa a constituição do indivíduo atento e do indivíduo desatento no interior do processo histórico de biologização moral da atenção. Em nossa tese, a história da biologia moral da atenção está dividida em três momentos principais: a segunda metade do século XVIII; a segunda metade do século XIX; as últimas três décadas do século XX. A investigação do terceiro momento está no centro da pesquisa. Nele, damos prioridade a análise da constituição do diagnóstico do Transtorno do Déficit de Atenção e Hiperatividade TDAH. Nos três períodos analisados, os interesses pelos estudos da atenção se intensificaram e seu controle e gestão tornaram-se objeto das tecnologias morais, sociais, econômicas, médicas e psicológicas. Neles a capacidade de controle da atenção passou a ser o que distinguia o sábio do tolo; o indivíduo senhor de si do alienado; o sujeito ativo, mestre no controle de seu corpo e de sua vontade, do impulsivo, portador de um corpo descontrolado e de uma vontade fraca. No século XVIII, a atenção era a direção ativa da mente que possibilitava o conhecimento racional do mundo e de si. Ela deveria ser treinada, incitada e estimulada. Aos que se dedicavam à sua disciplina e mestria era concedido um lugar privilegiado. A moral da atenção se constituía. Ao vinculá-la aos conceitos de inibição e de vontade, o século XIX lhe outorgou uma outra função: o controle do comportamento. Além de ser importante para a constituição do conhecimento, a atenção tornou-se responsável pela regulação da ação. Um novo valor da atenção se constituía. O século XIX também possibilitou que sua moral fosse naturalizada, atada ao corpo e, em seguida, "cerebrizada. O século XX vinculou a atenção à moral do sucesso e da produtividade e radicalizou o processo de sua cerebrização. No processo de moralização e valorização da atenção, as histórias da constituição do sujeito (des)atento são extremamente diversas. A versão analisada em nosso trabalho dialoga com a história do sujeito cerebral. A constituição do sujeito atento e do sujeito desatento é analisada nos espaços fronteiriços criados entre a moral e a biologia cerebral da atenção.

Ética publicitária em tempos hipermodernos: um estudo comparativo entre Brasil e Espanha

Esta tese tem como objetivo geral investigar conceitos, agentes e significações da ética publicitária que caracterizam os atuais tempos hipermodernos. Para tanto, os seguintes objetivos específicos foram traçados: levantar o que as organizações de auto-regulamentação do setor e os profissionais do mercado (não pertencentes a tais instituições) definem como ética publicitária; comparar tais olhares com princípios éticos hipermodernos ligados principalmente ao mercado e com reflexões de estudiosos sobre o tema, e realizar, ao final, um estudo comparativo entre os cenários brasileiro e espanhol de resultados obtidos. Os organismos estudados no Brasil e na Espanha (Madrid) foram, respectivamente, o CONAR Conselho Nacional de Auto-Regulamentação Publicitária, e a AUTOCONTROL Asociación para la Autorregulación de la Comunicación Comercial, e os profissionais abordados consistiram em publicitários e profissionais de marketing de empresas escolhidos segundo os critérios de acessibilidade, volume de anúncios veiculados sob sua criação/responsabilidade, e indicações de entrevistados. Os objetivos citados foram alcançados por meio de dois abrangentes conjuntos de iniciativas, a saber: 1) entrevistas com 63 pessoas (além dos diretores das organizações), estando entre elas, publicitários das áreas de criação e atendimento/planejamento de agências de propaganda, profissionais de marketing de empresas de setores diversos, e integrantes do Conselho de Ética do CONAR e órgão correlato na AUTOCONTROL. Como resultado geral desta pesquisa, pode-se dizer, entre outros, que, embora se apregoe atualmente que a ética hipermoderna está associada a um vazio ético ou a uma ética privada, a qual chega inclusive a distanciar-se do significado original do termo, ambos os organismos estudados demonstraram em vários momentos contrariar tais teorias, mesmo sendo eles concebidos e mantidos pelo próprio mercado. Apesar disso, nota-se, tanto nestas organizações, quanto entre os profissionais entrevistados, principalmente brasileiros, alguns indicadores que parecem refletir tais visões mais pessimistas ou que talvez dificultem o surgimento de uma postura mais ética, afastando-se, inclusive, de preceitos específicos de uma ética hipermoderna aplicada diretamente ao mercado. O cenário parece mais favorável no contexto espanhol, onde foram encontrados um maior número de instituições (além da AUTOCONTROL), documentos normativos e profissionais dedicados a defender a ética publicitária num sentido mais profundo do que somente combatendo a propaganda enganosa quanto a informações técnicas sobre os produtos ofertados.

Preditores de resiliência ao transtorno de estresse pós-traumático: uma metanálise

Ao contrário da maioria dos transtornos psiquiátricos, o transtorno de estresse pós-traumático (TEPT) apresenta uma fator causal necessário, embora não-suficiente: a exposição a um evento traumático (EPT). Em consequência deste evento desenvolvem-se três dimensões de sintomas: revivescência, esquiva/ entorpecimento emocional e hiperexcitabilidade. Um dos achados mais relevantes das pesquisas epidemiológicas de TEPT é que embora a maioria dos indivíduos seja exposta a um evento traumático em algum momento de sua vida, apenas uma minoria destes vai desenvolver o transtorno. Desta forma, a maior parte dos indivíduos expostos pode ser considerada resiliente. A resiliência consiste, portanto, na capacidade de adaptação eficaz diante de um distúrbio, estresse ou adversidade. Foi realizada uma revisão sistemática com metanálise de estudos longitudinais que investigaram fatores preditores de resiliência ao desenvolvimento de TEPT. A ausência de TEPT foi considerada proxy de resiliência. Em função do grande número de estudos identificados pela estratégia de busca, decidimos post hoc restringir as variáveis preditoras a apoio social (AS), personalidade, autoestima e eventos de vida potencialmente estressantes (EVPE). Apenas vinte artigos preencheram os critérios de elegibilidade. Treze estudos avaliaram apoio social, nove avaliaram personalidade e dois avaliaram EVPE. Nenhum dos trabalhos que pesquisou autoestima era elegível. Dezesseis dos vinte estudos incluídos nesta revisão avaliaram a associação de interesse na população geral. A maioria dos trabalhos avaliou a exposição de interesse após o EPT. Ainda que alguns destes tenham tentado captar a informação sobre a exposição antes do ocorrido, devido à natureza retrospectiva desta aferição, não há como se isentar o potencial efeito do trauma sobre resultado obtido. Além disso, foi observada grande heterogeneidade entre as pesquisas, limitando o número de estudos incluídos nas metanálises. Neuroticismo foi a única dimensão de personalidade avaliada por mais de um estudo. As medidas sumárias resultantes da combinação destes trabalhos revelaram que maior apoio social positivo prediz resiliência ao TEPT enquanto neuroticismo reduz a chance de resiliência. Os dois estudos que investigaram EVPE não puderam ser combinados. Um deles foi inconclusivo e o outro demonstrou associação entre menor número de EVPE e resiliência. Ressaltamos que as medidas sumárias devem ser interpretadas com cautela devido à grande heterogeneidade entre os estudos. Heterogeneidade na forma de avaliação dos fatores preditores de resiliência ao TEPT é compreensível devido à complexidade dos construtos avaliados. Todavia, a falta de padronização do método de operacionalização reduz a comparabilidade dos resultados.

Vivenciando a amamentação e sensações de prazer sexual e/ou excitação sexual ao amamentar: significados de mulheres

Trata-se de uma pesquisa com abordagem qualitativa e descritiva, com a utilização da Grounded Theory, na perspectiva do Interacionismo Simbólico. Como objetivos tivemos: identificar os significados atribuídos por mulheres ao fato de experimentar, sentir ou vivenciar sensações de prazer sexual e/ou excitação sexual durante a amamentação; analisar e interpretar, na perspectiva do Interacionismo Simbólico, a experiência de sentir prazer sexual e/ou excitação sexual durante a amamentação, a partir dos significados atribuídos pelas mulheres. O estudo procedeu-se no Município do Rio de Janeiro, em lugares de grande circulação de pessoas, como praças, ruas, shoppings, além da Unidade de Saúde Milton Fontes Magarão, localizada na zona norte do referido Município. Essa variedade de cenários nos possibilitou encontrar uma diversidade de participantes, referente a condições socioeconômicas, culturais, religião, ideais e concepções sobre o assunto estudado. A coleta e análise dos dados aconteceram no período de maio a julho de 2014, observando todas as exigências da Resolução 466/2012 do Conselho Nacional de Saúde. Foram entrevistadas 17 participantes e formados dois grupos amostrais e três categorias expressas por: significando a amamentação como ato sagrado, inocente e assexuado: a socialização da amamentação; vivenciando e significando sensações de prazer ao amamentar; ressignificando a vivência de sensações de excitação sexual ao amamentar. Como resultados evidenciou-se que a socialização da amamentação influencia a maioria das mulheres, na vivência de sensações de prazer ao amamentar. Essas sensações são descritas através da simbologia estabelecida socialmente, de que o ato de amamentar é sagrado, puro, livre de erotismo, prevalecendo um prazer maternal. Além disso, as sensações de excitação sexual ao amamentar, para as mulheres que se dizem nunca terem vivenciado, estão presentes no seu inconsciente, porém essa vivência é admitida para os outros e não para si mesmas. O significado de vivenciar prazer sexual ao amamentar é percebido como contraditório, pois ao mesmo tempo em que se identifica o poder do corpo feminino, prevalece o poder de nutrir sobre as percepções físicas de excitação sexual ao amamentar. Desse modo, identificaram-se estratégias utilizadas para bloquear ou para não vivenciar as sensações de excitação sexual ao amamentar. Com isso, este estudo nos mostra como as mulheres agem frente às sensações de prazer sexual e/ou excitação sexual ao amamentar, através da interação social do passado e do presente, gerando os significados que cada uma carrega consigo. Além disso, percebemos como a socialização da amamentação priva a vivência da sexualidade feminina, nos aspectos de sensações de prazer sexual durante a amamentação.

Comparação das variáveis fisiológicas e psicológicas em diferentes configurações de exercícios aeróbios

Existem diversas recomendações de treinamento aeróbio. Contudo, exercícios auto-ajustados têm sido indicados sob a premissa de gerar melhor resposta afetiva (ex.: prazer) gerando possivelmente maior chance de adesão. Diante da baixa adesão ao exercício e considerando seus benefícios, é necessário verificar que atividade gera melhor resposta afetiva. Esta dissertação investiga esta questão e é composta por dois estudos. Comparar as respostas fisiológicas e afetivas geradas por duas recomendações de treinamento aeróbio. Vinte e quatro participantes realizaram 3 sessões em esteira rolante. Foram determinados o nível de atividade física (questionário IPAQ) e o VO2Max. Nas visitas 2 e 3 foram aplicadas as recomendações aeróbias, uma baseada no nível de atividade física (PBPA) e outra baseada no VO2Max (PBVO2Max). Os dados foram divididos em quartis (Q). A PBPA gerou risco 150% maior de abandono da sessão de treino. O tamanho do efeito (TE) mostrou maior resposta afetiva (escala de sensações) para a PBVO2Max no Q4 (TE 0,41) e menor FC na PBVO2Max (TE médio dos quartis -0,85). Comparar as respostas fisiológicas e afetivas de atividades impostas e auto-ajustadas. Catorze participantes realizaram 3 sessões em cicloergômetro. O VO2Max foi determinado na visita 1. Na visita 2 foi realizada uma atividade AA e na visita 3 uma atividade imposta. Não foram encontradas diferenças significativas entre as atividades AA e imposta nas variáveis fisiológicas (FC, VO2, e lactato; p>0,05), na potência (p>0,05) e nas variáveis perceptivas (esforço percebido, escala de sensações e escala de ativação; p>0,05). Prescrições baseadas no VO2Max parecem proporcionar melhor resposta afetiva. O tipo de prescrição realizada (auto-ajustada ou imposta) parece não influenciar a resposta afetiva dos indivíduos. Os achados sugerem que um ajuste adequado do treino pode gerar melhores respostas afetivas

个体人格类型与气味偏好的关系

So far the studies on personality are based on indirect way due to the complexity and limitation. Present research attempt to find another route to approach personality through olfaction. The framework of present research is on account of a modern personality theory model produced by the British psychologist Eysenck. The aim of present research is to prove a correlation between olfaction and personality because sensation and perception of the olfaction on special part of brain closely related to emotional arousal. This research was carefully designed and performed by both psychological questionnaire and olfaction examination. The results indicated some good correlation between smell sense and personal character, which can by applied into personality and behavior analysis.

共情、共情唤醒机制及共情结果的关系

Empathy was defined as affective experience isomorphic to another person’s affective experience elicited by the person’s affective state in this research. By constructing questionnaires and situational measurement approaches, the relationship among empathy, perspective-taking, imagination, empathic concern, distress, and interconnectedness and helping was analyzed. Perspective-taking and imagination were regarded as arousal mechanisms of empathy. Empathic concern and distress were reactive outcomes of empathy. Interpersonal outcomes of empathy were discussed in this research were empathic interconnectedness and helping. The results showed that perspective-taking had significant positive influence on empathic concern. Empathy partly mediated the effects of perspective-taking on empathic concern. Influence of imagination on empathic distress was partly mediated by empathy also. Perspective-taking had significant negative influence on empathic distress. Empathy had direct effects on its reactive outcomes, and indirect effects on its interpersonal outcomes mediated totally by empathic concern. Classification analysis according to the relationship among empathy, its arousal mechanisms, and reactive outcomes of empathy showed that disposition of empathic reactivity could be divided into 4 styles: general high empathy (22.5%), general low empathy (25.7%), empathic concern (24.4%) and empathic distress (27.3%). 4 styles were different in interpersonal acuity and mental health. It was suggested that adaptive function of 4 styles was different. And the styles of disposition of empathic reactivity significantly predicted situational empathy and its intrapersonal and interpersonal outcomes.

情绪干扰下焦虑水平对执行抑制的影响机制——事件相关电位研究

Behavioral inhibition model suggests the generation of anxiety is related with over-inhibition. For knowing about anxiety better, we used event-related potential (ERP) technique to explore the underlying mechanism of executive inhibition under the emotional distracter in high and low trait-anxious groups. Firstly, we set up the Chinese affective picture system (CAPS) as the stimuli of subsequent experiments. Secondly, we screened the high and low trait-anxious participants using the State-Trait Anxiety Inventory. In the first ERP study, a modified oddball paradigm was used with the positive, neutral and negative pictures as novel stimuli and the potentials evoked by three types pictures were analyzed. In the second ERP study, the same paradigm with higher task load was employed to examine the interaction of anxious level and emotion. Main results as follows: 1. CAPS consisted of 852 pictures was assessed via three dimensionalities, valence, arousal and dominance. The standard deviation of scores on valence and dominance was more than the standard deviation of scores on dimension of arousal. Scatter plot showed that the score distributing on the dimension of valence and arousal was wide in CAPS. 2. In both high and low trait-anxiety groups, the amplitudes of N2 and P3 of negative pictures were greater and smaller respectively as compared with neutral and positive pictures, which suggested all participants no matter what anxious level required more inhibition processing to negative information than others. 3. With increasing of task load, the P3 amplitudes of negative pictures in high anxious group were reduced relative to neutral pictures. In addition, in high anxious group, the P3 amplitudes of positive pictures had the same changes as those of negative ones. Whereas, the reduced P3 of positive pictures were not observed in low anxious group. The results showed the high anxious participants employed the same inhibitory strategy to the positive distracter as the negative distracter, which possibly the over-inhibition processing was involved in this group. 4. Dipole source analysis found cingulate may be involved in executive inhibition processing. In sum, as for the inhibition, high and low anxious group both is sensitive to negative information. However, in the high load situation, due to the shortness of cognitive resources, the high anxious individual represents the general sensitivity to all emotional information. These results gave the electrophysiological evidence for over-inhibition in high trait-anxiety group.

负性情绪对分泌型免疫球蛋白A的影响以及事件相关电位的关联变化

Although the influence of emotional states on immune function has been generally recognized, researches on the effects of negative emotion on individual SIgA levels have reported mixed findings. Our study aimed to elucidate the relationship between changes in EEG activity and cognitive and psychological mechanisms to the immune changes induced by negative emotion. In experiment one, we investigated how the negative emotional arousal that was induced by watching a number of unpleasant pictures altered the concentration of secretory immunoglobulin A (SIgA). Although our results found discrepancies in the changing tendency of SIgA concentration among participants (some participants’ SIgA decreased after watching unpleasant pictures, whereas others increased), further analysis revealed a coherency among the changing of SIgA concentration, participants’ general coping styles and their actual emotion regulation strategies in perceiving unpleasant pictures, and the event-related potentials (ERPs) associated with the watching of unpleasant pictures. The participants whose SIgA increased after watching unpleasant pictures (the increasers) had higher positive coping scores in the Trait Coping Styles Questionnaire (TCSQ) than those whose SIgA decreased (the decreasers). Also, relative to the decreasers, the increasers tended to use more emotion regulation strategies especially when the presented pictures were extremely negative and exhibited a reverse dissociation pattern between the extremely negative pictures and the moderately negative ones in the amplitude of late positive potential (LPP) that was related to the cognitive evaluation of stimuli’s meaning. On this basis, Event-related potentials were recorded first while participants passively viewed unpleasant pictures, and then during an emotion regulation block in which participants were instructed to reappraise unpleasant pictures in the experiment two. We also collected the immune index before and after the passive viewing block and the emotion regulation block. Our study proved that participants felt a less intense emotional response to unpleasant pictures that followed a reappraisal instruction. The decreasing emotional responding to unpleasant pictures decreased the amplitude of the LPP. But larger N2 was induced in the emotion regulation block, because the participants needed to obtained more attentional resources to detect and integrate more stimulus features to use the cognitive reappraisal strategy effectively. The present study has important theoretic and practical significance. For the theoretic significance, our study elucidated the relationship between changes in EEG activity and cognitive and psychological mechanisms to the immune changes induced by negative emotion by using the technologies of ERP, experimental interview and psychological measurement. Meanwhile, our study also provided an explanation for the different changing tendencies of SIgA induced by negative emotions, and it plays an important role in further studying the cognitive neural mechanisms of immune level in response to emotion. As to the practical significance, our study suggests that individuals who use active emotion regulation in the face of negative emotion stimuli may experience significantly increases in immune system function, subsequently lowering the possibility of infection.

迁移性安慰剂效应的多模态机制 ：从痛觉到情绪的行为、ERP和fMRI研究

Although studies on placebo effect proved the placebo expectation established by pain-alleviating treatment could significantly alleviate later pain perception, or the placebo expectation established by anxiety-reducing treatment could significantly reduce the intensity of induced negative feelings, it is still unclear whether or not the placebo effect can occur in a transferable manner. That is, we still don’t know if the placebo expectation derived from pain-alleviating can significantly reduce later negative emotional arousal or not. Experiment 1: We compared the effect of the verbal expectation (purely verbal induction and without pain-alleviating reinforcement) with the reinforced expectation (building the belief in the placebo’s ataractic efficiency on unpleasant picture processing by secret reduction of the intensity of the pain-evoking stimulus) on the negative emotion. The results showed that the expectation, which was reinforced by actual analgesia, was transferable and could produce significant placebo effect on negative emotional arousal. However, the expectation that was merely induced by verbal instruction did not have such power. Experiment 2 both examined the direct analgesic effect of the placebo on the sensory pain (how strong is the pain stimulus) and emotional pain (how disturbing is the pain stimulus) and the transferable ataractic effect of the placebo on the negative emotion (how disturbing is the emotional picture stimulus), and further proved that the placebo expectation that was established from pain-reducing reinforcement not only induced significant placebo effect on pain, but also significant placebo effect on unpleasant feeling. These results support the viewpoint that the reduction of affective pain based on the conditioning mechanism plays an important role in the placebo analgesia, but can’t explain the transferred placebo effect on visual unpleasantness. Experiment 3 continued to use the paradigm of the reinforced expectation group and recorded the EEG activities, the data showed that the transferable placebo treatment was accompanied with decreased P2 amplitude and increased N2 distributed, and significant differences between the transferable placebo condition and the control condition (i.e., P2 and N2) were observed within the first 150-300 ms, a duration brief enough to rule out the possibility that differences between the two conditions merely reflect a bias “to try to please the investigator. In Experiment 4, we selected the placebo responders in the pre-experiment and let them to go through the formal fMRI scan. The results found that the transferable placebo treatment reduced the negative emotional response, emotion-responsive regions such as the amygdala, insula, anterior cingulate cortex and the thalamus showed an attenuated activation. And in the placebo condition, there was an enhanced activation in the subcollosal gyrus, which may be involved in emotional regulation. In conclusion, the transferable placebo treatment induced the reliable placebo effect on the behavior, EEG activity and bold signal, and we attempted to discuss the pychophysiological mechanism based on the positive expectancy.

消费者特征对其网络购物态度和行为意向的影响

In recent years, global online shopping grows rapidly, China's growth rate is far greater than the average level of the world. Online shopping as a new type of shopping patterns gradually drew the researcher's attention. There were so many existing researches on the relationship between consumer characteristic and online shopping attitude and intention, but few togethered the different abstract levels of consumer characteristic in one research. In this study, 3M Model was introduced as theory guide of whole research work, the Chinese consumers who knew about the online shopping was the research object, questionnaire survey was used to collect the data, different abstract levels of consumer characteristic were togethered in a hierarchical model, tried to establish a model to explain the relationship between different abstract levels of consumer characteristic and online shopping attitude and intention. In addition, the study also compared the models posed by data from different consumer groups. The results showed that: First, consumers’ openness, need for arousal, assessment of online shopping experience, perceived risk of online shopping would affect their online shopping attitude and online shopping intention. Second, openness, need for arousal indirectly influenced the online shopping intention through the perceived risk of online shopping. Third, the perceived risk of online shopping indirectly influenced the online shopping intention through online shopping attitude. Fourth, assessment of online shopping experience indirectly influenced the online shopping intention through the perceived risk of online shopping and online shopping attitude. Fifth, only online shopping attitude would directly affect online shopping intention. It also worked as a mediator variable in the final model. Sixth, network age, risk propensity did not significantly affect the online shopping attitude and online shopping intention. Seventh, freight fluctuation can affect student more than in-service on online shopping intention.

'Psyching-up' and muscular force production

Tod, D. A., Iredale, F., Gill, N. (2003). 'Psyching-up' and muscular force production. Sports Medicine, 33 (1), 47-58. RAE2008

Neural Control of Interlimb Coordination and Gait Timing in Bipeds and Quadrupeds

1) A large body of behavioral data conceming animal and human gaits and gait transitions is simulated as emergent properties of a central pattern generator (CPG) model. The CPG model incorporates neurons obeying Hodgkin-Huxley type dynamics that interact via an on-center off-surround anatomy whose excitatory signals operate on a faster time scale than their inhibitory signals. A descending cornmand or arousal signal called a GO signal activates the gaits and controL their transitions. The GO signal and the CPG model are compared with neural data from globus pallidus and spinal cord, among other brain structures. 2) Data from human bimanual finger coordination tasks are simulated in which anti-phase oscillations at low frequencies spontaneously switch to in-phase oscillations at high frequencies, in-phase oscillations can be performed both at low and high frequencies, phase fluctuations occur at the anti-phase in-phase transition, and a "seagull effect" of larger errors occurs at intermediate phases. When driven by environmental patterns with intermediate phase relationships, the model's output exhibits a tendency to slip toward purely in-phase and anti-phase relationships as observed in humans subjects. 3) Quadruped vertebrate gaits, including the amble, the walk, all three pairwise gaits (trot, pace, and gallop) and the pronk are simulated. Rapid gait transitions are simulated in the order--walk, trot, pace, and gallop--that occurs in the cat, along with the observed increase in oscillation frequency. 4) Precise control of quadruped gait switching is achieved in the model by using GO-dependent modulation of the model's inhibitory interactions. This generates a different functional connectivity in a single CPG at different arousal levels. Such task-specific modulation of functional connectivity in neural pattern generators has been experimentally reported in invertebrates. Phase-dependent modulation of reflex gain has been observed in cats. A role for state-dependent modulation is herein predicted to occur in vertebrates for precise control of phase transitions from one gait to another. 5) The primary human gaits (the walk and the run) and elephant gaits (the amble and the walk) are sirnulated. Although these two gaits are qualitatively different, they both have the same limb order and may exhibit oscillation frequencies that overlap. The CPG model simulates the walk and the run by generating oscillations which exhibit the same phase relationships. but qualitatively different waveform shapes, at different GO signal levels. The fraction of each cycle that activity is above threshold quantitatively distinguishes the two gaits, much as the duty cycles of the feet are longer in the walk than in the run. 6) A key model properly concerns the ability of a single model CPG, that obeys a fixed set of opponent processing equations to generate both in-phase and anti-phase oscillations at different arousal levels. Phase transitions from either in-phase to anti-phase oscillations, or from anti-phase to in-phase oscillations, can occur in different parameter ranges, as the GO signal increases.

A Neural Pattern Generator that Exhibits Frequency-Dependent In-Phase and Anti-Phase Oscillations

This article describes a. neural pattern generator based on a cooperative-competitive feedback neural network. The two-channel version of the generator supports both in-phase and anti-phase oscillations. A scalar arousal level controls both the oscillation phase and frequency. As arousal increases, oscillation frequency increases and bifurcations from in-phase to anti-phase, or anti-phase to in-phase oscillations can occur. Coupled versions of the model exhibit oscillatory patterns which correspond to the gaits used in locomotion and other oscillatory movements by various animals.