NEURAL MECHANISMS OF EMOTIONAL REGULATION AND DECISION MAKING

Emotions influence our perception and decision making. It is of great importance to understand the neurophysiology behind these processes as they influence human core functions. Moreover, knowledge within this field is required in order to develop new medical therapies for pathological conditions that involve dysregulation of emotions. In this thesis the neural mechanisms of emotional regulation and decision making were investigated using different pharmacological manipulations and brain imaging. In Study I, we examined whether a CCKb-receptor and a mu-opioid receptor agonist could modulate emotional perception of visual stimuli in opposite directions. In Study II and III, we examined if amygdala, a subcortical structure involved in emotional coding, was involved in social punishment and neural processing of unfairness. The participants played an economic game that examined their proneness to hand out social punishment and their processing of unfairness. Prior to the game, participants had been treated with either an active drug (oxazepam or madopark) or placebo. With this intervention we could manipulate the participants‟ behavior and brain activity. Lastly, in Study IV we investigated neural mechanisms of hypothetical bias; that is, the difference between a real decision versus a hypothetical decision. In summary we found, in Study I, that the CCK-opioid system can modulate emotional visual perception in opposite directions. In Study II we demonstrate that amygdala is involved in social punishment and neural processing of unfairness. The degree to which participants gave out social punishment was suppressed with oxazepam without affecting the participants‟ perception of unfairness. In Study III we noted that madopark increased amygdala activity in response to unfairness without detectable changes in behavior. In Study IV, we showed that real decisions, in comparison to hypothetical decisions, involve amygdala processing and amygdala activity co-varies positively with the real cost for the participants. In conclusion, this thesis demonstrates that specific neuromodulatory systems participate in emotional regulation and decision making. Our findings also prompt an ethical discussion as we show that a commonly used drug influences core functions in the human brain that underlie individual autonomy and decision making. SAMMANFATTNING PA SVENSKA Kanslor paverkar var upplevelse av varlden och var formaga att fatta beslut. Det ar darfor viktigt att forsta de underliggande hjarnprocesser for dessa fenomen eftersom de paverkar pa grundlaggande manskliga beteenden. Kunskap inom omradet kravs for att kunna utveckla nya medicinska behandlingar for sjukdomstillstand dar bristande kanslomassig reglering ar ett problem. I denna avhandling utredde vi vilka delar av hjarnan som reglera vara kanslor och beslutsfattning samt vilka amnen i hjarnan som styr dessa processer. Vi studerade detta genom att paverka forsoksdeltagarnas beteende med lakemedel samtidigt som vi undersokte deras hjarnaktivitet. I Studie I utredde vi huruvida tva lakemedel (pentagastrin och remifentanil) kunde paverka upplevelsen av kanslomassiga bilder i motsatta riktningar. I Studie II och III undersokte vi om amygdala, en “primitiv” hjarnstruktur som bearbetar kanslor, var inblandad i social bestraffning och bearbetning av orattvisa. Deltagarna spelade ett ekonomiskt spel, som undersokte deras benagenhet att utdela social bestraffning och bearbetning av orattvisa, samtidigt som de mottagit antigen en aktiv lakemedelsbehandling oxazepam (lugnande lakemedel) eller madopark (stimulerande lakemedel), eller ett sockerpiller. Saledes, kunde vi paverka deras beteende och hjarnaktivitet. I Studie IV undersokte vi vilka delar av hjarnan som ligger bakom “hypotetisk paverkan”, det vill saga, skillnaden mellan att fatta ett riktigt beslut jamfort med att ta ett hypotetiskt beslut. I korthet rapporterar vi, i Studie I, att pentagastrin och remifentanil kan paverka kanslomassiga synintryck i motsatta riktningar. I Studie II visar vi att amygdala deltar i social bestraffning och bearbetning av rattvisa. Graden av att utdela social bestraffning minskade med oxazepam utan att paverka deltagarnas upplevelse av orattvisa. I Studie III demonstrerar vi att madopark okade amygdala aktivitet som svar pa orattvisa utan att markbart paverka beteende. I Studie IV visar vi att riktiga beslut i jamforelse med hypotetiska beslut involverar amygdala. Sammanfattningsvis, visar denna avhandling att specifika hjarnomraden respektive vissa amnen i hjarnan deltar i regleringen av kanslor och beslutsfattning. Vara fynd uppmanar aven till en etisk debatt da vi visat att vanligt forekommande lakemedel kan paverka beslutsfattning utan att paverka ens fornimmelse av situationen. LIST OF PUBLICATIONS I. Gospic K. , Gunnarsson T. , Fransson P., Ingvar M. , Lindefors N. , Petrovic P. (2008) Emotional Perception Modulated by an Opioid and a Cholecystokinin Agonist. Psychopharmacology 197(2):295-307. Reproduced with kind permission from Springer Science and Business Media. II. Gospic K. , Mohlin E. , Fransson P., Petrovic P., Johannesson M, Ingvar M. (2011) Limbic Justice Amygdala Involvement in Immediate Rejection in the Ultimatum Game. PLoS Biology 9(5):e1001054. III. Gospic K. , Mohlin E. , Fransson P., Petrovic P., Johannesson M, Ingvar M. (2011) Limbic Justice Revisited – Dopamine Fuels Social Punishment. Submitted. IV. Gospic K. , Sundberg M. , Mader J., Fransson P., Petrovic P., Isacsson G. , Karlstrom A. , Ingvar M. (2011) Altruism Costs the Cheap Signal from Amygdala. Submitted. ADDITIONAL PUBLICATION I. Olofsson JK. , Gospic K. , Petrovic P., Ingvar M. , Wiens S. (2011) Effects of Oxazepam on Affective Perception, Recognition, and Event-Related Potentials. Psychopharmacology 215(2):301-309.