Social anxiety disorder : Functional neuroimaging and social cognitive features

Doruyter, Alexander Govert George (2018-03)

Thesis (PhD)--Stellenbosch University, 2018.

Thesis

ENGLISH SUMMARY : Neuroimaging has enabled important progress in understanding the neurobiology of social anxiety disorder (SAD). Functional neuroimaging experiments in SAD have mostly focused on regional neural activity in response to anxiety provocation or processing of emotional faces, and have found hyper-activations in limbic and paralimbic circuitry. Relatively little however, is known about resting-state conditions in SAD and how these are affected by pharmacotherapy. What is known is almost entirely based on functional magnetic resonance imaging (fMRI) techniques which, while powerful, have some important limitations. Similarly, there has been only limited work investigating the resting neural correlates of social cognitive biases in SAD; how reward processing is disrupted in the condition; and how these respective features are affected by therapy. This thesis presents the first work on SAD investigating resting functional connectivity (RFC) based on nuclear neuroimaging methods. In an experiment that analysed RFC based on single photon emission computed tomography with technetium-99m hexamethyl propylene amine oxime, it was found that RFC differences in SAD were largely consistent with a contemporary network model based on fMRI, as well as implicating disrupted connectivity of the cerebellum. Another novel finding was how pharmacotherapy in SAD increased RFC of the anterior cingulate cortex. Using graph theory and resting-state fMRI, the first evidence of reduced global efficiency and increased clustering coefficients within the theory-of-mind network in SAD as well as independent evidence of social attribution bias in the same sample were reported. In an experiment that investigated regional resting metabolism in the disorder, there was evidence of abnormality in SAD compared to controls, as well as evidence of pharmacotherapy effects, in several biologically relevant regions. These results merit further investigation. Finally, in an fMRI-based experiment on reward processing in SAD, initial results identified no evidence of disrupted processing on a monetary reward task. The findings here support a neurobiological model of SAD in which alterations in resting regional metabolism may underlie disruptions in resting brain networks that have been implicated as being important in social cognitive processing. The results also suggest that pharmacotherapy may affect resting-state conditions through compensatory effects. Finally, the provisional findings are consistent with the theory that reward deficits in SAD may be limited to the processing of social reward, and may not extend to the processing of other reward types. Future SAD research should focus on collaborative work, using pooled datasets, and place greater emphasis on molecular disruptions in neurotransmitter systems involved in the disorder.

AFRIKAANSE OPSOMMING : Breinbeelding het belangrike vooruitgang in ons begrip van die neurobiologiese onderbou van sosiale angssteuring (SAS) moontlik gemaak. Funksionele breinbeeldingseksperimente in SAS het tot dusver meestal gefokus op aktiwiteit in spesifieke areas in reaksie op die ontlokking van angs of tydens die verwerking van emosionele gesigsuitdrukkings, en resultate het op hiperaktiwiteit in limbiese en paralimbiese kringe gedui. Relatief min is egter bekend oor rustende breintoestande in SAS en hoe dit deur farmakoterapie geraak word. Wat wel bekend is, berus grootliks op tegnieke van funksionele magnetiese resonansie beelding (fMRB). Hierdie tegnieke, hoewel kragtig, het enkele belangrike beperkings. Daar is ook min bekend oor die veranderlikes in die brein wat verband hou met die disfunksionele kognitiewe sosiale vooroordele tipies van SAS, oor die verwerking van beloning in SAS, en hoe hierdie eienskappe deur terapie geaffekteer kan word. Hierdie proefskrif sluit die eerste SAS-data oor rustende funksionele konnektiwiteit (RFK) in die brein – wat gebaseer is op kerngeneeskundige reinbeeldingsmetodes – in. Hierdie bevindinge oor RFK (wat gebaseer is op enkelfoton-emissie-rekenaartomografie wat technesium-99m heksametielpropileenamienoksiem gebruik), stem grootliks ooreen met 'n kontemporêre netwerkmodel wat op fMRB gebaseer is, en dat die RFK van die serebellum in SAS ontwrig is. Nog ʼn nuwe bevinding is dat farmakoterapie in SAS RFK van die anterior singulaat korteks verhoog. Deur gebruik te maak van grafiese teorie en fMRB in die rustende toestand, word die eerste bewyse van verminderde globale doeltreffendheid en verhoogde trosvormingskoëffisiënte binne die “theory-of-mind” breinnetwerk in SAS, sowel as onafhanklike bewyse van sosiale attribusie vooroordele (“social attribution bias”) in die steuring gelewer. Na aanleiding van ʼn ondersoek oor rustende metabolisme in sekere brein-areas in SAS, word abnormaliteite in SAS in vergelyking met gesonde kontrolepersone gerapporteer, sowel as bewyse van die effek van farmakoterapie op verskeie biologies-relevante areas gelewer. Hierdie resultate regverdig verdere navorsing. Ten slotte, in 'n fMRB-gebaseerde eksperiment oor die verwerking van beloning in SAS was daar geen bewyse van ontwrigte verwerking in monetêre beloning nie. Hierdie bevindinge ondersteun 'n neurobiologiese model van SAS waarin veranderinge in rustende metabolisme in sekere brein-areas onderliggend is aan die ontwrigting van rustende brein-netwerke wat belangrik is tydens sosiale kognitiewe prosessering. Die bevindinge dui ook daarop dat farmakoterapie RFK in SAS beïnvloed, moontlik via die aktivering van kompenseringsmeganismes. Ten slotte, die voorlopige resultate stem ooreen met die teorie dat tekorte ten opsigte van die verwerking van beloning in SAS moontlik beperk is tot die prosessering van sosiale beloning, en dat dit nie veralgemeen kan word na die verwerking van ander beloningstipes nie. Toekomstige SAS-navorsing behoort op samewerking met ander navorsingsgroepe te fokus, sodat gesamentlike groter datastelle gebruik kan word. Bykomend hiertoe behoort daar groter klem te wees op ondersoeke na die ontwrigting op molekulêre vlak in die neuro-oordragstelsels van individue met SAS.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/103504
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