Many clients with developmental and/or intellectual disabilities (ID/DD) do not tolerate routine medical or dental procedures and may require intrusive interventions, including restraint of various types (i.e. chemical, mechanical, physical, etc.) during appointments. Graduated exposure, or stimulus fading, along with reinforcement for compliance, have been shown to increase cooperation and tolerance in some clients; however, many do not respond to these types of interventions. Nine participants diagnosed with ID/DD recieved compliance/tolerance training for routine medical or dental procedures. Results of these interventions were evaluated in the context of several potential indices of readiness, such as medical diagnoses, level of disability, and presence of challenging behavior, among others. Several of the variables appeared to be correlated with program responsiveness; however, a larger sample will be necessary to draw definitive conclusions. Client characteristics and past assessments (anecdotals, preference assessments, terminal probes, and survey data) were evaluated. The analytical framework developed for this analysis may be useful to future researchers and clinicians as a model for assessing readiness for tolerance training programs.

區辨性增強低頻反應作業 (differential reinforcement of low-rate responding task, DRL task) 為一與時間相關聯之操作式制約行為作業，該作業常用於計時行為、行為抑制功能、或抗焦慮與抗憂鬱症等藥物之行為藥理研究的探討。雖然DRL作業是一種實驗室常用的動物行為模式，但是對於上述行為或藥理機制的探討往往缺乏一致性的解釋，其中可能的原因為DRL作業的行為同時包含了計時與行為抑制的成份。針對上述問題，本研究將以DRL行為作業為研究主題，探討作業習得歷程之神經機制。首先根據DRL作業之行為內涵，將作業的習得分為行為抑制與計時先後表現的兩個階段；並依據過去的研究文獻整理出的八個與行為抑制和計時表現相關之大腦區塊，以c-Fos免疫組織化學染色法探討行為抑制和計時的神經機制。實驗結果發現受試於行為抑制的表現階段，其眶眼皮質、內側前額葉皮質、與海馬CA1區域的c-Fos表現量較高；而在計時行為的表現階段，除了和行為抑制有關的三個大腦區塊外，尚有前扣帶迴、紋狀體、與齒狀迴呈現c-Fos表現量增加的現象。綜合以上結果，DRL-10秒作業於學習初期所進行的行為抑制可能和前額葉皮質與海馬體的神經互動有關；而學習較末階段的計時表現，則可能需要前額葉皮質、紋狀體、與海馬等三處較多的次級區域的組織加入，形成神經網路的方式支援之。 / Differential reinforcement of low-rate responding (DRL) task was an operant conditioned behavior based on temporal contingency. This task has been widely used to investigate the behavioral components of timing and behavioral inhibition, which is frequently used for pharmacological screening of anxiolytic and antidepressant drugs. Despite of being widely used as an animal behavioral model in the laboratory, but the performance of the DRL task was varied and inconsistent when the drug test conducted. One way to encounter this problematic issue is to differentiate the distinct behavioral components of DRL task and correlate the involved neural substrates, which was the theme investigated in the present study. This study first characterized the acquisition process of the DRL-10 sec task into behavioral inhibition and the timing stages, and then assessed the c-Fos levels by immunohistochemistry in the eight brain areas that potentially involved in behavioral inhibition and the timing processes. Regarding the stage of behavioral inhibition, significant increases in c-Fos-positive neurons were observed in the orbitofrontal cortex (OFC), the medial prefrontal cortex (mPFC), and the hippocampal CA1 area. At the stage of the timing being acquired, c-Fos immunohistochemical activity was highly expressed in the anterior cingulated cortex (ACC), OFC, mPFC, the dorsolateral striatum (dlS), the dentate gyrus (DG), and the hippocampal CA1 area. Together, these results showed that the functioning dual paths between the hippocampus CA1 and the prefrontal cortex (OFC and mPFC) are critically essential for developing the appropriate performance via behavioral inhibition in the early-stage of the DRL task and with three other areas (ACC, dlS, and DG) being recruited, an anatomical circuitry connecting prefrontal/striatal/hippocampal structures were involved in the acquisition of interval timing toward the later establishment of the DRL behavior.

Made available in DSpace on 2016-04-29T13:17:47Z (GMT). No. of bitstreams: 1 Carolina Krauter Kracker.pdf: 3705226 bytes, checksum: 2d14824d7cb8a26f483a95c38dd83639 (MD5) Previous issue date: 2013-05-03 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Metacontingencies are the product and the process of selection of cultural practices in the third level of selection by consequences, in which variation is a fundamental requisite for selection to occur. Three experiments were conducted with the objectives of investigate the effects of schemes analogous to differential reinforcement schemes of variability LAG, and CRF, upon the behavior variability in cultural selection processes, and to ascertain in which ways more or less variability along these processes would affect the selection of a new metacontingency, in the face of a change in the cultural consequences presentation criterion. In the Experiment I, 21 participants worked in trios, under the effect of schemes analogous to LAG 2 and LAG 1 for the products of responses of inserting numbers from 0 to 9 in spots placed in some computers´ screens. It was required, as a condition to the presentation of cultural consequences (bonus), that an aggregate product (PA) featured by an specific relation among the sums of the numbers inserted by the participants and by non-repetition of the sums between cycles, according to the n of the LAG contingence, was produced. It was observed that there wasn´t systematic production of this PA along more than two consecutive generations of participants and that only the specified relation among sums recurred along different generations. Stereotypies in the operant responses´ topographies and in the sums were found. In the face of the change in the criterion of presentation of the cultural consequences, featured by a different relation among the sums (new PA), the selection of/ by metacontingencies and cultural transmission occurred and the production of stereotypies was again observed. In the second experiment, that counted on 14 participants, similar experimental phases were conducted, except that there wasn´t a phase in which schemes analogous to LAG were in effect. The selection of/by metacontingencies and its transmission were verified in these conditions, and when the change in the criterion of presentation of the cultural consequences was made, a new cultural selection was observed in a similar moment of the occurrence of this phenomenon in the previous experiment; the practice was also transmitted. Behavior stereotypies were noticed, mainly in the first process of cultural selection that was described. There were 18 participants in the third experiment, in which a scheme analogous to LAG 1 for the sums was introduced; after 13 generations of participants the selection of/by metacontingencies was ascertained, as well as its transmission. It was observed that there was more variability in the responses topographies and in the sums, but patterns that indicated restrictions in the behavior variability were identified when the cultural selection occurred. It was concluded that the introduction of schemes analogous to LAG hampered the selection of/by metacontingencies and that a new cultural selection happened rapidly, despite of more or less behavioral variability in the microcultures´ stories previously the modification of the criterion related to the presentation of cultural consequences / Metacontingências são o produto e o processo de seleção de práticas culturais no terceiro nível de seleção por consequências, em que variação é requisito fundamental para ocorrência de seleção. Três experimentos foram conduzidos com os objetivos de investigar os efeitos de esquemas análogos a esquemas de reforçamento diferencial de variabilidade LAG e CRF em relação à variabilidade comportamental em processos de seleção cultural; e de averiguar de que maneira maior ou menor variabilidade ao longo desses processos afetariam a seleção de uma nova metacontingência, diante de uma mudança no critério de apresentação das consequências culturais. No Experimento I, 21 participantes trabalharam em trios, vigorando esquemas análogos a LAG 2 e LAG1 em relação a produtos das respostas de inserção de números de 0 a 9 em caselas dispostas nas telas de computadores. Exigiu-se, como condição para a apresentação de consequências culturais (bônus), que um produto agregado (PA) caracterizado por uma determinada relação entre as somas dos números inseridos pelos participantes e pela não-repetição das somas entre ciclos, de acordo com o n do LAG, fosse produzido. Observou-se que não houve produção sistemática desse PA por mais de duas gerações consecutivas de participantes e que apenas a relação entre as somas especificada recorreu por diversas gerações, observando-se estereotipias nas topografias das respostas operantes e nas somas. Diante da mudança no critério de apresentação da consequência cultural, caracterizada por uma relação diferente da anterior entre as somas (novo PA), ocorreu a seleção de/por metacontingências e transmissão cultural, novamente observando-se a geração de estereotipias. No segundo experimento, que contou com 14 participantes, fases experimentais semelhantes foram conduzidas, exceto que não houve uma fase em que esquemas análogos a LAG vigoraram. Averiguou-se que a seleção de/por metacontingências e sua transmissão ocorreram nessas condições e, diante de mudança no critério de apresentação da consequência cultural, nova seleção cultural foi observada em momento próximo ao verificado no experimento anterior, ocorrendo também a transmissão da prática. Estereotipias comportamentais foram notadas, principalmente no primeiro processo de seleção cultural descrito. Houve 18 participantes no terceiro experimento, em que se implementou um esquema análogo a LAG 1 para as somas; após 13 gerações de participantes, a seleção de/ por metacontingências com esse esquema em vigor pôde ser constatada, bem como sua transmissão. Foi observada maior variabilidade nas topografias de respostas e somas, mas padrões que indicaram restrição na variação comportamental foram identificados diante da ocorrência da seleção cultural. Constatou-se que a introdução de esquemas análogos a LAG teve como efeito dificultar a seleção de/ por metacontingências e que uma nova seleção cultural ocorreu rapidamente a despeito de haver maior ou menor variabilidade comportamental nas histórias de microculturas, anteriormente à mudança de critério para apresentação da consequência cultural de microculturas.

Made available in DSpace on 2016-04-29T13:18:00Z (GMT). No. of bitstreams: 1 Dissertacao Thais Martins Sales.pdf: 1293785 bytes, checksum: 6161405c79ed51ec0c3dacacebe67ee1 (MD5) Previous issue date: 2006-05-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This study was an attempt to investigate possible relations between responding that is reinforced according to schedules based on a temporal parameter and performing other activities to which no reinforcement contingencies are programmed. These activities have been called adjunctive behavior, collateral behavior or interim activities. Two questions guided this study: a) is there any difference in response rate, average time between reinforcers, and percentage of reinforced responses when an FI schedule or a DRL schedule is in force, if the subject can engage in other activities; b) are typical sequential patterns developed between responses when these schedules are in force? Four male food deprived rats were subjects of this experiment. The apparatus was an experimental box with seven chambers in which subjects could perform different activities, such as bar pressing, eating, running, drinking, and wood-chewing. For two subjects, bar pressing was reinforced according to three DRL schedules (DRL 4s, DRL 5s, and DRL 20s). One of the subjects was first kept in the chamber with the bar and food dispenser and then was allowed to access the other chambers, the other was first allowed to access the other chambers and then was kept in the chamber with the bar and food dispenser. For the other two subjects, bar presses were reinforced according to two FI schedules (FI 5s and FI 10s). One of the subjects first had access to all chambers and then was kept in the chamber with the bar and food dispenser, and the other was kept in the chamber with the bar and food dispenser during the whole experiment. Bar presses, reinforcement deliveries, and occupancy of chambers were recorded. Results show there was a difference in response rate, average time between reinforcers, and percentage of reinforced responses in both schedules, depending on the access condition, mainly when responses were reinforced according to schedules higher than FI 5s and DRL 4s. Higher response rates, lower average time between reinforcers and higher percentage of reinforced responses were observed for the DRL subjects when access was possible than when it was not possible, and higher response rates, higher average time between reinforcers and higher percentage of reinforced responses were observed for the FI subjects when access was possible than when it was not possible. No typical sequential patterns were observed when access was possible and either of the two studied schedules was in force. Results are discussed in terms of possible controlling variables to performing activities other than bar pressing when responding is being reinforced according to FI and DRL schedules / O presente trabalho é uma tentativa de investigação de possíveis relações entre o responder reforçado segundo dois esquemas de reforçamento que envolvem parâmetros temporais e o engajamento em atividades para as quais não há reforço programado, chamadas de atividades ínterim, comportamento adjuntivo ou comportamento colateral. Duas perguntas dirigiram a realização deste trabalho: a) há diferença na taxa de respostas, tempo médio entre reforços e porcentagem de respostas reforçadas segundo esquemas DRL e FI, caso haja possibilidade de engajamento em outras atividades? e b) alguma seqüência típica de engajamento em outras atividades é formada no intervalo entre respostas reforçadas segundo estes esquemas? Os sujeitos do experimento foram quatro ratos machos privados de alimento. Foi utilizada uma caixa experimental com sete compartimentos, nos quais era possível o engajamento em diferentes atividades: pressionar a barra, comer, beber, correr, roer madeira. Dois sujeitos tiveram as respostas de pressão à barra reforçadas segundo esquemas DRL com três valores diferentes (4s, 9s e 20s). Um deles passou, primeiro, por uma condição na qual o acesso a todos os compartimentos era permitido, chamada de aberta, e, segundo, por uma condição na qual era mantido no compartimento onde havia a barra e o comedouro, chamada de fechada, e o outro sujeito passou, primeiro, pela condição fechada e, segundo, pela condição aberta. Os outros dois sujeitos tiveram as respostas de pressão à barra reforçadas segundo esquemas FI com dois valores diferentes (5s, 10s). Um sujeito passou primeiro pela condição aberta e, depois, pela condição fechada e o outro passou apenas pela condição fechada. As pressões à barra, os reforços e a permanência nos compartimentos foram registrados. Os resultados mostraram que houve diferença na taxa de respostas, tempo médio entre reforços e porcentagem de respostas reforçadas em função da condição de acesso, especialmente quando as respostas de pressão à barra foram reforçadas segundo o esquema DRL 9s e DRL 20s, para os dois primeiros sujeitos, e segundo o FI 10s, para os outros dois sujeitos. Na condição aberta com esquema DRL em vigor, observou-se uma menor taxa de respostas, menor tempo entre reforços e maior porcentagem de respostas reforçadas do que na condição fechada, com o mesmo esquema em vigor. Na aberta com esquema FI em vigor, observou-se uma menor taxa de respostas, maior tempo entre reforços e maior porcentagem de respostas reforçadas do que na condição fechada, com o mesmo esquema em vigor. Seqüências típicas de engajamento em outras atividades não foram observadas quando o acesso era possível e o responder era reforçado segundo os esquemas FI e DRL. Os resultados são discutidos em termos de possíveis variáveis que controlam o engajamento em outras atividades, quando respostas são reforçadas segundo estes dois esquemas

Made available in DSpace on 2016-04-29T13:18:08Z (GMT). No. of bitstreams: 1 Livia Ferreira Godinho Aureliano.pdf: 559598 bytes, checksum: 8bc000da4999e46895b037747380a514 (MD5) Previous issue date: 2008-04-30 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This study investigated the effects of duration exposure to activities without programmed reinforcers on performance under a temporal schedule of reinforcement. Two other questions guided this study: (a) Are there any changes in the patterns of activities that occur without programmed reinforcers dependent on the duration of exposure to these activities? (b) What would be the effect of the duration of this exposure over responding under a DRL schedule of reinforcement when subjects are placed in a standard operant chamber without access to other activities? Subjects were 4 male food deprived rats and 2 chambers were used: a standard operant chamber (1 compartment with lever and food recipient) and a 7 compartment chamber (activity chamber) in which subjects could engage on different activities: as bar pressing, eating, drinking, wood-chewing, and running. Bar presses were reinforced with food according to a DRL schedule that varied from 5 to 10 to 21s, but 2 subjects were exposed to this schedule on the standard chamber and the others on the activity chamber. Experimental sessions lasted 2 hours and bar presses, reinforce deliveries, and compartments visited were recorded. Results indicated performances in teach environment when DRL 10s or higher was in effect. On DRL 10s response and reinforcer rates and percentage of reinforced responses were higher, and time between reinforcements was lower for subjects on the standard chamber. In DRL 21s, however, these measures were reversed, suggesting that the availability of other activities could facilitate the acquisition and maintenance of performance on higher values DRL. There was indication of an increase on the percentage of reinforced bar pressing responses as a function of time of exposure to the experimental contingency in each session for all subjects. There were no significant differences on the percentages of reinforced responses of subjects on the standard or activity chamber box as a function of successive experimental sessions. However, percentages of reinforced responses were lower for subjects in the standard chamber at the beginning of the first sessions on each DRL value. Sequences of compartment visits, that seemed to be patterns were identified and the beginning of this patterns coincided with the increased effectiveness of the bar pressing responses. Results are discussed taking into account the differences between the criteria used in studies reported on the literature. The possible roles of the activities on the performance submitted on DRL schedules are also discussed / O presente estudo pretendeu investigar os efeitos do tempo de exposição dos sujeitos às atividades sem reforço programado sobre a efetividade do desempenho submetido a um esquema temporal de reforçamento. Duas outras perguntas nortearam o trabalho: (a) ocorreria alguma mudança nos padrões das atividades sem reforço programado em função do tempo de exposição a estas atividades? (b) qual o efeito do tempo de exposição aos diferentes valores do esquema DRL sobre o desempenho dos sujeitos na caixa padrão? Foram sujeitos 4 ratos machos, privados de alimento, que trabalharam em duas caixas experimentais, uma com 7 compartimentos nos quais havia a possibilidade de engajamento em atividades (pressionar a barra, comer, beber, roer madeira, correr na roda de atividades) e uma caixa operante padrão. As respostas de pressão à barra dos 4 sujeitos foram submetidas a um esquema DRL5s, 10 e 21s : 2 sujeitos foram expostos aos esquemas na caixa padrão e os outros dois na outra caixa. Todas as sessões experimentais tiveram a duração de 2 horas. Foram registradas as pressões à barra, os reforços obtidos e o tempo de permanência nos compartimentos. Os resultados indicaram que as maiores diferenças entre os desempenhos nos dois ambientes ocorreram a partir do DRL 10s, quando as taxas de respostas, de reforços e as porcentagens de respostas reforçadas foram maiores, e o tempo entre reforços foi menor para os sujeitos na caixa padrão. Em DRL 21s, no entanto, a situação se inverteu, sugerindo que a disponibilidade de outras atividades poderia facilitar a aquisição e adaptação do desempenho em valores mais altos do DRL. A análise dos efeitos do tempo de exposição à contingência em cada sessão sobre a efetividade da resposta de pressão à barra indicou que as porcentagens de respostas reforçadas aumentaram em função do tempo da sessão para os 4 sujeitos e não houve diferenças expressivas entre as porcentagens de respostas reforçadas ao longo das sessões experimentais. No entanto, para os sujeitos na caixa padrão, os percentuais alcançados no início das primeiras sessões em cada fase foram mais baixos do que para os sujeitos em ambiente aberto. Em relação ao padrão das atividades, uma seqüência de visita a compartimentos foi identificada e o início deste padrão coincidiu com o aumento da efetividade das respostas de pressão à barra. A discussão dos resultados leva em consideração as diferenças entre os critérios utilizados nos estudos relatados, além dos possíveis papéis das atividades sobre o desempenho submetido ao esquema de DRL

No description available.

Le trouble du spectre de l’autisme se caractérise par la présence de difficultés au plan de la communication sociale et par la présence de comportements répétitifs et d’intérêts restreints (American Psychiatric Association, 2013). Les enfants ayant un TSA présentent plusieurs difficultés concomitantes qui les rendent plus susceptibles de vivre des niveaux de stress élevés, comme des déficits dans la sphère de la communication, de la socialisation et des fonctions exécutives, ainsi que la présence de particularités sensorielles (Groden et al., 1994, 2005). Malgré que ces enfants soient plus à risque de vivre du stress, plusieurs enjeux méthodologiques rendent difficile sa mesure et plus particulièrement chez ceux qui sont non verbaux. Pour ces raisons, le recours aux mesures physiologiques pour évaluer le stress auprès de cette clientèle est d’une grande pertinence. Par contre, les sensibilités sensorielles de ces enfants pourraient les rendre plus susceptibles de ne pas tolérer ces mesures. Le premier article de cette thèse vise donc à évaluer l’efficacité de l’intervention comportementale renforcement différentiel d’autres comportements (differential reinforcement of other behavior; DRO) pour augmenter la tolérance au port d’une ceinture cardiaque chez deux enfants non verbaux ayant un TSA. Les résultats obtenus démontrent que cette intervention a été efficace pour amener ces enfants à augmenter leur tolérance au port du dispositif cardiaque. Un autre aspect qui a reçu beaucoup d’attention dans les dernières années est l’implication du stress dans l’explication des comportements répétitifs et stéréotypés chez les personnes ayant un TSA. Les résultats des études antérieures sont contradictoires (de Vaan et al., 2018; Gabriels et al., 2013; Hutt et al., 1975; Lydon et al., 2015; Yang et al., 2015) et ont principalement utilisé des mesures indirectes des comportements répétitifs. Pour cette raison, le deuxième article de cet ouvrage vise à évaluer le lien entre le cortisol salivaire, le rythme cardiaque et des mesures d’observations directes de la stéréotypie chez quatre enfants minimalement verbaux ayant un TSA. Les résultats montrent que le cortisol et le rythme cardiaque sont significativement liés à la stéréotypie globale et motrice, sans que ces liens soient observés avec la stéréotypie vocale. Finalement, mesurer directement les comportements stéréotypés demande beaucoup de ressources, ce qui pourrait expliquer la prépondérance des mesures indirectes dans les études. Comme pour l’évaluation du stress, il importe de réfléchir aux méthodes alternatives abordables et accessibles qui pourraient améliorer la mesure de ces comportements. Le troisième article de cette thèse a évalué l’efficacité d’un algorithme d’intelligence artificielle (IA) dans la reconnaissance de la stéréotypie vocale chez des enfants ayant un TSA. Les résultats démontrent que la performance de l’algorithme est supérieure à la reconnaissance due au hasard. Bien que des recherches futures soient nécessaires pour augmenter l’efficacité de cette méthode, l’IA représente une technologie novatrice ayant le potentiel d’améliorer significativement les méthodes actuellement utilisées pour mesurer la stéréotypie. En conclusion, le présent ouvrage explore différentes avenues novatrices pour mieux comprendre et de monitorer la stéréotypie chez les enfants ayant un TSA. / Autism spectrum disorder (ASD) is characterized by the presence of difficulties in social communication and the presence of repetitive behaviors and restricted interests (American Psychiatric Association, 2013). Children with ASD have several concurrent difficulties, such as deficits in communication, socialization, and executive function, as well as the presence of sensory peculiarities that make them more likely to experience high levels of stress (Groden et al., 2005). Although these children are at increased risk for stress, a number of methodological issues make it difficult to measure, particularly in non-verbal children. For these reasons, the use of physiological measures to assess stress among this group is highly relevant. On the other hand, the sensory sensitivities of these children could potentially make them more likely to be intolerant to these measures. Therefore, the first study in this thesis aims to evaluate the effectiveness of differential reinforcement of other behavior (DRO) to increase compliance with wearing a heart rate monitor in two non-verbal children with ASD. The results obtained portray that this intervention was effective in getting these children to increase their compliance to wearing a cardiac device. Another aspect that has received much attention in recent years is the involvement of stress in explaining repetitive behaviors in individuals with ASD. However, the results of previous studies have been producing contradictory results (de Vaan et al., 2018; Gabriels et al., 2013; Hutt et al., 1975; Lydon et al., 2015; Yang et al., 2015), and have mainly been using indirect measures of stereotypy. For this reason, the second study in this thesis aims to evaluate the relationship between salivary cortisol, heart rate, and direct observational measures of stereotypy in four minimally verbal children with ASD. The results show that cortisol and heart rate are significantly related to global and motor stereotypy, but not to vocal stereotypy. Finally, measuring stereotypy requires a lot of resources, which could explain the preponderance of indirect measuring in studies on stress. As with the measurement of stress, it is important to consider affordable and alternative methods that could improve the measurement of these behaviors, and therefore the third study evaluated the effectiveness of an artificial intelligence (AI) algorithm in the recognition of vocal stereotypy in children with ASD. The results show that the performance of the algorithm is superior to recognition due to chance. Although future research is needed to increase the effectiveness of this method, AI represents an innovative technology with the potential to significantly improve the methods currently used to measure vocal stereotypy. In conclusion, this thesis explores different innovative methods to better understand and monitor stereotypy in children with ASD.

本研究利用兩種時間關聯之操作式制約行為作業探討韁核的行為功能，一為區辨性增強低頻反應作業（簡稱DRL作業），另一為固定時距作業（簡稱FI作業）。本研究以神經毒素鵝膏蕈酸（ibotenic acid）破壞韁核的方式來測試大白鼠受試在上述行為作業之不同歷程的影響效果，包含習得歷程、行為表現階段以及已習得後轉換得酬賞之反應標準等三個階段。實驗一的結果顯示破壞韁核對於DRL作業的習得歷程具有明顯的影響，其影響效果在DRL短時距作業中造成無法以有效率的壓桿反應模式獲得酬賞；反之，破壞操弄的效果並不影響FI長與短時距作業的習得歷程。實驗二的結果顯示破壞韁核並不影響已習得的DRL作業與FI作業的行為表現，兩項作業的實驗組受試皆能維持穩定的行為反應模式且與控制組無明顯差異。實驗三對已習得的DRL行為進行時距參數的轉換（含調高及降低兩部份），結果顯示破壞韁核之操弄並未明顯的影響這項轉換新的時距之作業要求，但實驗組受試的確比控制組較遲緩達到新的時距要求。綜合而言，本研究以專屬性較高的神經毒素破壞韁核，用較多元指標的行為分析方式探討韁核的行為功能；其結果發現韁核參與DRL行為內含的區辨學習與對於錯誤偵測的負向迴饋，這些功能是需要透過韁核與其他中腦及邊緣系統的組織互動。 / This study examined the function of habenula (Hb) by two kinds of operant conditioned behavior tasks based on temporal contingency, including the differential reinforcement of low-rate responding (DRL) task and fixed-interval (FI) task. The effects of Hb lesion induced by neurotoxin ibotenic acid were examined at the different stages of operant conditioned behavior, including acquisition, performance, and transition stages. The results showed that bilateral lesions of Hb did not affect the locomotor activity and the basic lever-pressing. In Experiment 1, Hb lesion group had less reinforced responses and lower peak time indicating the deficits of acquisition of the DRL task. In contrast, the same lesion manipulation on the FI task did not produce any difference between the lesion group and the control group. The data of Experiment 2 showed that Hb lesion did not significantly affect the learned behavior maintained on DRL-10s or FI-30s schedule. In Experiment 3, Hb lesion produced a subtle, but not significant, impairment on behavioral transition from a learned interval to a newly-set interval (upward or downward). The lesioned subjects made a slower transition than the controls. In conclusion, these data suggest that the function of habenula is involved in discrimination learning and error detection for acquiring DRL behavior. However, it is likely that these Hb functions have to rely upon dynamic relationship between Hb and other midbrain limbic systems.

透過神經科學的研究，對於大腦的行為功能已有一定的認識，不同於以往的認識，目前認為神經行為機制不只由單一腦區或單一神經化學系統所調控。深部大腦電刺激經常被用來研究特定腦區的行為功能。但是，深部大腦電刺激的作用機制仍然不清楚。最近幾年臨床研究發現，利用電刺激在側韁核成功的治療憂鬱症患者。然而，目前認為側韁核與多巴胺系統互為負回饋作用，共同參與在動機行為的酬賞反應中。本實驗室先前的研究顯示，破壞韁核造成區辨性低頻操作式制約行為 (簡稱DRL行為)學習的障礙，然而，電刺激在側韁核造成DRL行為表現的結果還是未知的。所以，本實驗主要以電刺激在側韁核觀察大鼠行為上的改變，探討側韁核在行為上參與的功能。實驗一的結果顯示電刺激在側韁核並不影響自發性運動能力，在不同電流強度的刺激下也不會影響。實驗二的結果顯示電刺激在側韁核造成DRL 15秒的行為有類安非他命效果之行為表現，在高頻率電刺激有較顯著類安非他命的效果。實驗三的結果顯示電刺激在側韁核造成DRL 15秒的行為之影響，會被多巴胺受體抑制劑所抵消，而單獨注射巴胺受體抑制劑並不影響DRL 15秒的行為。實驗四的結果顯示電刺激在側韁核造成DRL 15秒的行為之影響，不會被正腎上腺素受體抑制劑所抵消。實驗五的結果顯示電刺激在側韁核造成DRL 72秒的行為之影響並不如DRL 15秒的行為顯著。實驗六的結果顯示電刺激在側韁核並不會造成大鼠無法區辨酬賞的量。綜合而言，側韁核在動機行為的角色，是透過影響多巴胺系統造成行為的改變。 / Behavioral function of the brain has been studied in neuroscience and progressively accumulated informative data to reveal the neurobehavioral mechanisms. It is now realized that those underlying mechanisms of behaviors is not as such simple as previous thought of limiting only in one locus of the brain or solely by one neurochemical system. The deep brain stimulation is usually used to study the behavioral function of specific brain regions. However, the mechanism of the deep brain stimulation is still unclear. The previous study has shown that electrical stimulation of the lateral habenula (LHb) successfully treated depression symptoms in the patients. It is proposed that an inhibitory role of LHb on the mibrain dopamine (DA) system which mediates the reward-related behavior. A previous study of this lab showed that lesion of habenula impaired the acquisition of differential reinforcement of low-rate responding (DRL) behavior. But, the effect of LHb stimulation on the DRL behavior is still unclear. To determine the functions of LHb involving in the behavior, the electrical stimulation was applied in LHb to observe the behavioral change of rats. The results of Experiment 1 showed that the LHb stimulation had no effect on locomotor activity. In Experiment 2, the LHb stimulation was shown to affect DRL 15-s behavior, which effects were similar to those affected by amphetamine. Experiment 3 showed that the DA receptor antagonists reversed the effects of LHb stimulation, while experiment 4 showed that norepinephrine (NE) receptor antagonists had no reversal effect on DRL 15-s behavior. In Experiment 5, the amphetamine-like behavior induced by LHb stimulation had subtle effects on DRL 72-s behavior. Experiment 6 showed that the LHb stimulation had no effect on a discrimination task. These data suggest that the LHb modulating DRL behavior is DA-dependent.

周邊注射安非它命能夠影響動物受試在表現與時間知覺有關的操作式制約行為作業，歷來被研究者認為是大腦多巴胺神經系統與動物時間知覺系統有關的主要證據之一。本研究所共同採用的研究方法為先注射多巴胺受體專屬拮抗劑再於大鼠受試周邊腹腔注射安非它命的方式探討安非它命影響大鼠時間知覺的大腦機制為何。實驗一利用區辨性增強低頻反應作業觀察周邊注射多巴胺受體專屬拮抗劑何者可以反制周邊安非它命對此作業的影響效果，結果發現多巴胺D1受體拮抗劑SCH23390與D2受體拮抗劑raclopride均可反制周邊安非它命的效果。實驗二同樣利用區辨性增強低頻反應作業，但是將SCH23390與raclopride分別注入海馬迴、背側中區紋狀體、腹側側邊紋狀體、依核、內側前額葉皮質以及腹側頂蓋區等六個部位，觀察何種多巴胺受體拮抗劑可在那些大腦部位產生反制周邊安非它命的效果。結果發現SCH23390可在海馬迴、依核、內側前額葉皮質以及腹側頂蓋區等四個部位產生反制周邊安非它命的效果，而raclopride可在腹側側邊紋狀體與內側前額葉皮質兩個部位產生同樣的反制效果。實驗三利用高峰時距作業觀察SCH23390在海馬迴與內側前額葉皮質是否能反制周邊安非它命對此作業的影響效果，結果發現SCH23390僅在海馬迴會影響大鼠受試的正常表現，特別是在與周邊安非它命同時注射的時候。綜合以上結果顯示，周邊注射安非它命能夠使大鼠受試在區辨性增強低頻反應作業當中表現出時間知覺變快的傾向，這個效果需要同時透過大腦內的海馬迴、依核、內側前額葉皮質以及腹側頂蓋區的多巴胺D1類受體和腹側側邊紋狀體與內側前額葉皮質的多巴胺D2類受體。 / The central dopaminergic system has been hypothesized to play a role in time perception based on the results that peripheral injections of d-amphetamine alter the responses in time-related operant conditioned behavioral tasks. The present study investigated the effect by injecting specific dopamine receptor antagonists before peripheral d-amphetamine injections in rats. Data from Experiment I showed that both peripheral the dopamine receptor D1 antagonist SCH23390 and D2 antagonist raclopride could attenuate the response alteration on differential reinforcement of low-rates responding task induced by peripheral d-amphetamine. By using the DRL task, Experiment 2 employed the microjeciton technique to determine the neural substrates for the DA receptor antagonist to attenuate the effect of peripheral d-amphetamine. The infusion sites for DA receptor antagonist were the hippocampus, the dorsomedial striatum, the ventrolateral striatum, the nucleus accumbens, the medial prefrontal cortex, and the ventral tegme ntal area. The results showed that SCH23390 infused into the hippocampus, the nucleus accumbens, the medial prefrontal cortex, the ventral tegmental area could attenuate the effect induced by peripheral d-amphetamine, and such attenuation effects were also observed for raclopride infused into the ventrolateral striatum, the medial prefrontal cortex. Experiment 3 tried to confirm the results of Experiment 2 by microinjecting SCH23390 in hippocampus and medial prefrontal cortex under peak-interval task. Only SCH23390 in the hippocampus altered the subject's normal performance in this task especially when combined with peripheral injection of d-amphetamine. In conclusion, that the response alteration on the DRL task induced by peripheral injection ofd-amphetamine suggests the subject's timing perception being accelerated. These effects of d-amphetamine were mediated by simultaneous activation of multiple dopamine receptor subtypes including D1 receptors located in the hippocampus, nucleus accumbens, medial pref rontal cortex, ventral tegmental area, as well as D2 receptors located in the ventrolateral striatum, medial prefrontal cortex.