Anatomical variability of the human insula has not been well studied because the structure of the insula is difficult to image. Thus, the aim of this study was to apply a novel method to reconstruct insular topology in order to assess the anatomic variation within a population. An analysis of 60 healthy male and female subjects revealed a significant amount of anatomic variation. Some structures, such as the central sulcus were extremely stable and showed little inter-individual variability, while other structures such as the middle short gyrus were highly variable, being more conspicuous in the left hemisphere and in males. Grey matter in the cortex was found to be thinner in the left posterior and dorsal insular subregions in older female subjects but not males. This work shows that the insula is an anatomically complex and variable structure and that some of the variability is related to sex and laterality.

Anatomical variability of the human insula has not been well studied because the structure of the insula is difficult to image. Thus, the aim of this study was to apply a novel method to reconstruct insular topology in order to assess the anatomic variation within a population. An analysis of 60 healthy male and female subjects revealed a significant amount of anatomic variation. Some structures, such as the central sulcus were extremely stable and showed little inter-individual variability, while other structures such as the middle short gyrus were highly variable, being more conspicuous in the left hemisphere and in males. Grey matter in the cortex was found to be thinner in the left posterior and dorsal insular subregions in older female subjects but not males. This work shows that the insula is an anatomically complex and variable structure and that some of the variability is related to sex and laterality.

Eating disorders are difficult to treat: there is still no NICE-approved first-line treatment for anorexia nervosa. In part this could be due to a lack of a compelling theoretical model to account for the development and dogged persistence of the illness. Sociocultural factors implicating western preoccupation with thinness and attractiveness are likely to play a contributory role, but cannot be by themselves causal in societies where such ideals are dominant. Recent theoretical models in neuroscience predict that predisposing neurobiological factors in early brain development may render some young people more vulnerable than others to universal psychosocial pressures, especially during adolescence. This dissertation reviews the existing evidence for abnormal neurobiological functioning in eating disorders, acknowledging that it is difficult to distinguish between the acute effects of starvation on the brain and possibly pre-existing underlying factors. Nevertheless, such empirical studies do support the development of a novel hypothesis implicating abnormal functioning of a neural network centred on the insula cortex in anorexia nervosa. The insula hypothesis is tested in a series of functional imaging studies using Single Positron Emission Computed Tomography (SPECT) indicating focal abnormalities in the temporal region that persist following weight restoration treatment and correlate with neuropsychological deficits. A subsequent study using higher resolution functional Magnetic Resonance Imaging (fMRI) lends further partial support to the insula hypothesis (in three out of four tasks) and also implicates additional brain structures in the basal ganglia. These findings, if replicated, could contribute to the development of novel therapeutic approaches to the treatment of anorexia nervosa, including realtime fMRI and mindfulness-based approaches, both of which have been shown to modulate insula activation. The studies presented here could hopefully also help to reduce the stigma and shame so often associated with eating disorders, for the benefit of sufferers and their families.

Le cortex insulaire est le cinquième lobe du cerveau en charge de l'intégration de nombreuses fonctions cognitives, sous-tendues par une organisation cytoarchitectonique etune connectivité aussi riche que complexe. Ce travail vise à évaluer la connectivité fonctionnelle insulaire du cerveau humain par le biais de stimulation électrique intra-cérébrale et de potentiels évoqués cortico-corticaux (PECC) réalisés chez des patients explorés en stéréoélectroencéphalographie (SEEG) pour une épilepsie partielle réfractaire. Nous avons développé un protocole automatisé permettant destimuler successivement l’ensemble des bipoles d’enregistrement intracérébraux (deux plots contigus d’une même électrode) disponibles chez les patients explorés en SEEG. Deux sériesde 20 stimulations monophasiques d’une durée unitaire de 1 ms et d’une intentisté de 1 mA, étaient délivrés à une fréquence de 0,2 Hz au niveau de chaque bipole (105 en moyenne,produisant un total d’environ 11.000 PECC par patient). Un premier travail a consisté dans lamise au point d’une méthode fiable d’analyse statistique objective des PECC significatifs, encomplement de l’analyse visuelle, sur un échantillon de 33017 enregistrements chez trois patients. L’analyse a porté sur les quatre fenêtres temporelles post-stimulation suivantes: 10-100 ms, 100-300 ms, 300-500 ms, 500-1000 ms. La seconde partie de notre thèse a appliquéces méthodes à l’étude des connections intra-insulaires sur un échantillon de10 patients présentant au moins deux éléctrodes intra-insulaires. La dernière partie de notre travail s’est intéressé aux efférences insulaires sur un échantillon de 11 patients. L’étude des PECC apporte des éléments de connectivité fonctionnelle derésolution spatiale et temporelle inégalée, complémentaires de ceux découlant des techniquesde neuroimagerie. La gestion complexe du volume de données à gérer pour chaque patientpeut être résolu par des procédures d’analyse statistiques automatisée de sensibilité etspécificité satisfaisante. Le pattern des connections intra- et extra-insulaires révélé par cetteapproche permet une meilleure compréhension de la physiologie de l’insula chez l’Homme etdes modalités de propagations des décharges épileptiques impliquant ce lobe. / The insular cortex is the fifth lobe of the brain and is in charge of the integration of many cognitive functions, underpinned by a rich cytoarchitectonic organization and a complex connectivity. Our work aims to evaluate the insular functional connectivity of the human brain using intracerebral electrical stimulation and recording of cortico-cortical evoked potentials (CCEPs) in patients investigated with stereoelectroencephalography (SEEG) for refractory partial epilepsy. We first developed an automated protocol to stimulate successively all intracerebral recorded bipoles (two contiguous leads of the same electrode) available in patients undergoing SEEG. Two sets of 20 monophasic stimulation of 1 ms duration and 1mA intensity were delivered at a frequency of 0.2 Hz at each bipole (105 on average, producing a total of about 11,000 recordings per patient). We then develop a reliable and objective statistical method to detect significant CCEPs as a complement to visual analysis, and validate this approach on a sample of 33017 recordings in three patients. The analysis was performed over four distinct post-stimulus epochs: 10-100 ms, 100-300 ms, 300-500 ms, 500-1000 ms. In the second part of our thesis, we applied these methods to the study of intrainsular connections on a sample of 10 patients with at least two intra-insular electrodes. The last part of our work used the same approach to investigate insular efferents in a sample of 11 patients. The study of CCEPs provides novel and important findings regarding the human brain functional connectivity, with unmatched spatial and temporal resolutions as compared to neuroimaging techniques. The complex management of large volume of data in each patient can be solved by automated statistical analysis procedures with satisfactory sensitivity and specificity. The pattern of connections within and outside the insula revealed by this approach provides a better understanding of the physiology of the Human insula as well as of the propagation of epileptic discharges involving this lobe.

Bakgrund: Flera faktorer samverkar vid utvecklingen av anorexia nervosa och bidrar till sjukdomens komplexitet. Anorexia nervosa karakteriseras av bristande sjukdomsinsikt och låg kroppsvikt på grund av den starka strävan efter en smal kropp. Tillfrisknandet är en lång och svår process. Många som tillfrisknat från anorexia nervosa rapporterar att de fortfarande har en besatthet kring kroppen samt problematiska tankar. Det ökar intresset för om det går att tillfriskna helt och inte enbart enligt kriterier fastställda för anorexia nervosa. Intresset drivs av att insjuknade individer uppvisar förändringar i aktiveringsmönster i hjärnan. Insulära loben (insula) är ett område i hjärnan som integrerar flera olika processer och bidrar med upplevelsen av den egna kroppen. Hos individer med anorexia nervosa ses förändrat aktiveringsmönster i insula. Syfte: Denna studie syftar till att undersöka aktiveringsmönster i insula vid olika typer av stimuli hos individer som tillfrisknat från anorexia nervosa. Studien syftar till att närma sig sanningen i frågan om det finns premorbida drag i insula som predisponerar för utvecklingen av anorexia nervosa. Metod: Litteraturstudie. Utvalda tvärsnittstudier har granskats närmare där en tillfrisknad grupp jämförs med en grupp individer som aldrig diagnostiserats med anorexia nervosa. Resultat: Högre aktivering i anterior insula ses i en förväntnings fas inför presenterandet av bilder på mat (p<0.001). Under en förväntnings fas på smärtsam stimuli uppvisas även högre aktivering i anterior insula hos de tillfrisknade individerna (t-värdet 3.64). De tillfrisknade individernas subjektiva värdering av hur förväntnings fasen upplevdes korrelerade inte med uppmätt aktivitetsmönster. Lägre aktivering i posterior insula sågs hos RECAN gruppen då smärta upplevdes (t-värdet 5.10). Stimulering med sackaroslösning resulterade i lägre aktivering i anterior insula hos de tillfrisknade individerna (p=0.01). Stimulering med artificiellt sötningsmedel uppvisade ingen statistisk signifikant skillnad. Vid en felaktig förutsägelse sågs en högre aktivering i posterior insula hos den tillfrisknade gruppen (p<0.05). Antalet kopplingar av vita fibrer mellan insula och orbitofrontala cortex samt striatum är fler hos den tillfrisknade gruppen. Den microstrukturella integriteten av fibrer (fraktionerad anisotropi), mellan områdena är lägre än hos kontrollgruppen (p<0.007). Diskussion: Studien fann skillnader i insulas aktiveringsmönster hos individer som tillfrisknat från anorexia nervosa. För tillfrisknade individer skapar förväntnings fasen mer ångest än hos kontrollgruppen vilket aktiverar anterior insula. Missmatchen som konstaterades mellan individernas subjektiva värdering samt uppmätt aktiveringsmönster tyder på en dysfunktion i insulas uppgift att integrera interoceptiva processer som kan vara premorbida drag. BMI korrelationer mellan antalet kopplingar och de vita fibrernas microstrukturella integritet avsaknas vilket inte utesluter premorbida drag i insula. Slutsats: Studien kan inte svara på frågan om premorbida drag finns i insula. Studiens resultat föreslår att ett annorlunda aktiveringsmönster i insula kan vara en bidragande orsak till utvecklingen av anorexia nervosa. För ett säkrare svar behöver fMRI skanningar göras innan individen insjuknar. Resultatet från studien bidrar med förståelse för anorexia nervosas komplexitet samt varför risken för återfall är stor. / Background: Different factors co-operate in the development of anorexia nervosa and contribute to the complexity of the disease. Anorexia nervosa is characterized by a lack of insight about being ill and a low weight that is maintained with a desire to be thin. Recovery from anorexia nervosa is a difficult process. Many recovered individuals report that they still have problematic thoughts about food and problems with their body image. With that in mind there is an interest for the question if full recovery is possible. That means a recovery when the person feels recovered not just don´t meet the requirement for anorexia nervosa any longer. The question is supported by the fact that individuals currently ill in anorexia nervosa shows different activation patterns in the brain. The insula is a part of the brain that integrates different processes and contributes to the body image. Individuals currently ill in anorexia nervosa shows different activation patterns in the insula Aim of the study: This study aim to study activation patterns in the insula when different stimulus is presented for recovered individuals. The study aim to get closer to an answer if there is premorbid traits in the insula that predispose for the development of anorexia nervosa. Methods: Literature review. Selected cross-sectional studies are reviewed further where a group of recovered individuals is compared to a group of people that never been diagnosed with anorexia nervosa. Results: Greater activation of the anterior insula is notable during an anticipation phase when the individual anticipate pictures of food (p<0.001). Anticipation of painful stimuli also shows greater activation of the anterior insula in recovered individuals (t-value 3.46). The subjective ratings of how enjoyable the anticipation phase was didn´t correlate with the measurements of the activation pattern i the insula. The posterior insula showed lower activation during pain stimulation in the recovered group (t-value 5.10). The anterior insula showed lower response to the taste of sucrose in the recovered group. No statistic significant group differences were found when artificial sweeteners were present. Prediction error resulted in a greater activation in anterior insula in the recovered group (p<0.05). Higher structural white matter connectivity between insula, orbitofrontal cortex and striatum but less fiber integrity in the recovered group (p<0.007). Discussion: This study found different activation patterns in individuals recovered from anorexia nervosa. The anticipation phase creates more anxiety in the recovered group and the anterior insula shows greater activation. The mismatch between the subjective experience and the activation pattern in the insula suggest altered integration that might be a premorbid trait. The lack of BMI correlations between fiber structural connectivity and integrity supports the hypothesis about premorbid traits in insula. Conclusion: This study is unable to determine an answer to the question if there are premorbid traits in the insula. The results of this study propose that different activation patterns in the insula may predispose for the development of anorexia nervosa. The results contribute with a better understanding of the complexity of anorexia nervosa and why there is a huge relapse rate. fMRI before the individual develop anorexia nervosa could clarify the results.

Attention-deficit/hyperactivity disorder (ADHD) is characterized by hyperactivity, impulsive behavior, and excessive in attention. The diagnosis is divided into different types of ADHD depending on the symptoms. A single cause for the diagnosis has not been found; therefore, various models exist. When choosing between an immediate smaller reward and a later larger reward, ADHD-diagnosed individuals often choose the immediate smaller reward, termed choice impulsivity (CI). Several models have tried to explain this phenomenon. One theory argues that the subjective value of the reward diminishes when the reward is moved furtheraway in time. Others claim that it is a deficit in inhibitory-based executive dysfunction and that ADHD individuals cannot suppress the drive and resist the temptation of the earlier reward. The delay aversion model argues that it is a motivational problem with an abnormality in the reward mechanism making the patients hypersensitive to delayed rewards. The negative affective state that evokes from the delayed rewards makes them want to escape or avoid it and therefore choose the small, immediate reward. The insula and the amygdala mediate both negative and positive emotional processes in the brain and are candidates for this phenomenon. In this systematic review, four scientific studies were selected and included to investigate if the insula and amygdala are the primary CI candidates in ADHD-diagnosed individuals. The systematic review results support the idea that the amygdala correlates with CI in ADHD-diagnosed individuals, therefore supporting the delay aversion model theory of ADHD. A correlation between insula and CI in ADHD-diagnosed individuals could not be established in this systematic review. Understanding the role that emotional structures have in ADHD can help to develop interventions or therapy to cope with the disadvantaged features of ADHD.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18876号 / 医博第3987号 / 新制||医||1008(附属図書館) / 31827 / 京都大学大学院医学研究科医学専攻 / (主査)教授 髙橋 良輔, 教授 小泉 昭夫, 教授 宮本 享 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Current neurobiological models of adolescent decision-making suggest that heightened risk taking during adolescence is a result of the asynchronous development of neural regions underlying cognitive control and reward processing, particularly during periods of heightened social and affective arousal (e.g., Casey, Getz, & Galván, 2008; Steinberg, 2008). Despite the emphasis on the interplay of cognitive and emotional processes during adolescence, the developmental literature has largely overlooked the potential importance of maturational changes in the anterior insular cortex (AIC), a region known for its role as a cognitive-emotional hub. In a recent review we proposed a theory of adolescent risk-taking in which development of the AIC, and its connectivity to other regions, biases adolescents towards engagement in risky behaviors (Smith, Steinberg, & Chein, 2014b). The current studies provide a test of the proposed model through an examination of specific aspects of AIC development and functioning, including the trajectory of structural development within the AIC, the role of AIC engagement in adolescents' risky decision-making, and the impacts of affective arousal on AIC recruitment. Results from Study 1 suggest that the AIC exhibits continued developmental changes during adolescence that likely affect its involvement in cognitive processes. Using a risk-taking task, Study 2 demonstrates the flexible role of the AIC during adolescent decision-making and explores how affective arousal biases the AIC towards engagement in risky behaviors. Implications for both the proposed model and the developmental literature are discussed. / Psychology

Made available in DSpace on 2016-06-02T19:23:02Z (GMT). No. of bitstreams: 1 6369.pdf: 1124310 bytes, checksum: 0ca17967bc2f98ad5efcffdb78af91d5 (MD5) Previous issue date: 2014-05-09 / Universidade Federal de Minas Gerais / Empathy can be defined as the capacity for perceive emotional signals from others. Among these signals, the ability to perceive pain has clear adaptive and evolutionary value. Pain can be defined as a subjective experience that includes sensorial, emotional and cognitive components. Evidence has emphasized the role of amygdala, anterior cingulate cortex (ACC) and insula in modulation of pain and empathy. Research indicates the capacity of rodents to express empathy to a conspecific in pain or suffering. Works from literature and finds from our laboratory demonstrated that living together with a cagemate is able to alter the nociceptive behavior in mice. However, there are no works evidencing if occur alterations in nociception by living together with a cagemate with chronic pain and which encephalic structures would be involved in this modulation. To overcome this, male Swiss-albino mice were housed in groups or in pairs. The role of amygdala, ACC and insula are accessed by non-selective inactivation with cobalt chloride (CoCl2). Mice housed in groups (Experiment 1), aging 6-8 weeks, underwent a stereotaxic surgery. 4 to 5 days after surgery, these animals received saline or CoCl2 microinjection, and, after 10 minutes, they were submitted to the writhing test during 5 minutes (acetic acid 0.6%, i.p., nociceptive stimulus). On the dyads (Experiment 2), animals lived together for 28 days since weaning. On the 14th day, one animal of each pair were submitted to a sciatic nerve constriction (SNC animal) or not (sham animal). On the 24th day, the cagemate underwent a stereotaxic surgery, and, on the 28th day, they were submitted to the writhing test after microinjection of saline or CoCl2, like the procedure described to Experiment 1. To Experiment 1 were utilized Student s t test to independent samples; to Experiment 2 were utilized two-way analysis of variance (ANOVA; living together x treatment). Duncan s multiple range tests were utilized as post hoc. A p value of 0.05 or less was required for significance in both experiments. In Experiment 1, inactivation of the amygdala increased the number of writhing, while inactivation of ACC and insula did not alter this measure, suggesting a distinct modulatory role of these structures on the sensorial compound of pain. Our results demonstrated that for the mice that lived in groups, while inactivation of the ACC and insula did not change writhing, inactivation of amygdala increased it, suggesting a distinct modulatory role of these structures on sensory component of pain in the writhing test. In Experiment 2, living together with a SNC-cagemate increased writhing on the pair, suggesting that this experience activates the circuitry of neural representation of pain on the observer mouse (state of priming ). Thus, when this animal experienced nociception, its response was exacerbated. In this condition, inactivation of insula and amygdala produces opposite results, i.e., decreased and increased in contortions in those animals that lived together with a SNC animal, respectively. ACC inactivation did not alter writhing behavior. In this sense, our results suggest a different modulatory role of these structures on cognitive, affective-emotional and sensorial components of pain, and on empathy for pain. / Sob uma perspectiva evolucionista, a empatia é expressa pela capacidade de captar sinais emocionais nos outros. Neste sentido, a habilidade em perceber a dor também possui valor claramente adaptativo e evolutivo. A dor pode ser definida como uma experiência subjetiva que inclui componentes sensoriais, afetivo-emocionais e cognitivos. Evidencias apontam para o papel da amídala, córtex cingulado anterior (CCA) e insula na modulação da dor e da empatia. Estudos indicam para a capacidade de roedores em apresentarem empatia frente à dor ou ao sofrimento de seus coespecíficos. Trabalhos da literatura e do nosso grupo demonstram que a convivência em pares é capaz de alterar bidirecionalmente a resposta nociceptiva em camundongos. Entretanto, nenhum estudo havia ainda evidenciado se ocorrem alterações nociceptivas devido à convivência com um coespecífico em quadro de dor crônica, e quais estruturas encefálicas estariam envolvidas nessa modulação. Neste sentido, camundongos machos Suiço-albinos foram alojados em grupos ou em duplas para avaliação do papel da amídala, insula e córtex cingulado anterior por meio de inativação com cloreto de cobalto (CoCl2). Os animais alojados em grupo (Experimento 1), ao atingirem idade entre 6-8 semanas, passaram por cirurgia estereotáxica. De 4 à 5 dias após a cirurgia, esses animais receberam microinjeção de salina ou CoCl2 e, após 10 minutos, foram submetidos ao teste de contorções abdominais (ácido acético 0,6%, i.p., estímulo nociceptivo) durante 5 minutos. Nas duplas (Experimento 2), os animais conviveram por um período de 28 dias após o desmame. No 14º dia, um animal de cada par foi submetido à cirurgia de constrição do nervo ciático (animal CNC) ou não (animal sham). No 24º dia, o camundongo que conviveu com o animal CNC ou animal sham passou por uma cirurgia estereotáxica, e, no 28º dia, foi submetido ao teste de contorções abdominais, após microinjeção de salina ou CoCl2, conforme Experimento 1. Para o Experimento 1 foi utilizado o teste t de Student para amostras independentes; no Experimento 2 foi utilizada a análise de variância (ANOVA) de dois fatores (convívio x tratamento). O post hoc utilizado foi o teste de comparações múltiplas de Duncan. Os valores de p menores ou iguais a 0,05 foram considerados como significativos nos dois experimentos. No Experimento 1, a inativação da amídala aumentou o número de contorções, enquanto a inativação do CCA e da insula não alterou esse parâmetro, sugerindo um papel modulatório distinto dessas estruturas no componente sensorial da dor para o teste de contorções. No experimento 2, o convívio com um animal CNC aumentou o número de contorções no parceiro, sugerindo que essa convivência causou ativação dos circuitos de representatividade neural da dor no camundongo observador (state of priming ). Dessa forma, quando esse animal experiencia nocicepção, sua resposta é exacerbada. Nessa condição, a inativação da insula e amídala produziu resultados opostos, ou seja, diminuição e aumento das contorções naqueles animais que conviveram com o animal CNC, respectivamente. A inativação do CCA não alterou o número de contorções. Nesse sentido, nossos resultados sugerem um papel modulatório distinto dessas estruturas nos componentes cognitivo, afetivo-emocional e sensorial da dor, e na empatia para a dor.

Un pilier d'une vie sociale fructueuse est la capacité de prédire correctement les actions des autres et de percevoir leurs états émotionnels. Des études d'interaction sociale chez les primates ont montré qu'ils sont capables de déduire ce que les autres peuvent entendre ou voir, et de prédire leurs émotions et intentions. Il a été montré qu'ils peuvent manifester différents degrés de comportements prosociaux, allant de la coopération jusqu'à des comportements altruistes et empathiques. Des études d'imageries fonctionnelles chez l'homme ont identifié l'insula antérieur (AI) comme une région cérébrale clé dans le traitement de l'empathie.Spécifiquement, cette région apparait comme l'aire intégratrice des activités liées à la douleur ressentie et observée, suggérant que l'empathie pourrait impliquer un modèle « miroir » des propriétés affectives et sensorielles de la douleur d'autrui. Cependant, les bases neuronales de ce processus n'ont pas encore été découvertes. Dans le but d'examiner le rôle de l'AI dans le traitement de l'empathie, nous avons enregistré l'activité des neurones dans l'AI de deux singes pendant qu'ils sont engagés dans une tâche sociale leur permettant de délivrer un stimulus aversif ou appétitif à leur partenaire, à lui-même ou à personne. Les résultats comportementaux ont montré que les singes prennent en compte le bien-être de leur partenaire. Les données neuronales rapportent différentes populations neuronales répondant aux stimuli aversif ou appétitif et ceux délivrés à soi ou à autrui. Notamment, la population neuronale répondant au stimulus aversif a montré trois profils d'activité : une représentation neuronale de l'expérience désagréable du partenaire, une représentation neuronale de sa propre sensation désagréable et une minorité de neurones montrant des propriétés miroirs entre soi et autrui. Nos résultats suggèrent un modèle neuronal de l'empathie représentant des propriétés distinctes entre l'expérience vécue et observée / A cornerstone of a successful social life is the ability to correctly predict others’ actions and empathically perceive their emotional states. Studies on primates’ social interaction have shown that thanks to their keen cognitive abilities monkeys are able to deduce what others can hear or see, and to predict others’ emotions and intentions. It has been shown that primates are able to display different degrees of prosocial behavior, from cooperation to even altruism and empathically driven behavior. Studies using fMRI techniques inhumans have identified the anterior insula (AI) as a key brain region in the processing of empathy. More precisely, this region emerged as the overlapping area activated for both experienced and observed pain,leading to the idea that empathy for pain may involve a mirror-matching model of the affective and sensory features of others' pain. However, the neuronal basis of this process has yet to be uncovered. In an attempt toextend and to investigate the role of the AI in the process of empathy we have recorded single cell activity inthe AI of two monkeys while they were engaged in a social task where based on the performed trials positiveor negative reinforcements could be delivered to self, another monkey, or nobody. Behavioral results showed that monkeys take into account the welfare of their partners even when this has no impact on their ownwelfare. Our neuronal findings report that distinct population of neurons respond differentially to outcomesfor self and other, and to appetitive and aversive outcomes. Interestingly the neuronal population responding to the aversive outcome showed mainly three profiles of activity: neuronal representation of conspecifics’unpleasant experience, neuronal representation of own unpleasant experience and a minority of neurons showing mirroring properties between self and other. Thus, our results suggest a neuronal model of empathy that accounts for the distinctive features between feeling and empathizing