Empathic embarrassment is an emotional state that belongs to the self-conscious category of emotions. It is an uncomfortable condition where someone feels embarrassed over another person’s mishap or violation of social norms. It is prosocial in that one is motivated to help a person who expresses embarrassment. To experience it, one needs to be able to imagine how the other person is feeling and how one would feel if the situation happened to oneself. One is likelier to feel empathic embarrassment if one likes the person who is experiencing the mishap or if one has experienced the mishap oneself. This thesis investigates whether empathic embarrassment is a prosocial emotion and what neural basis empathic embarrassment has. The results show that empathic embarrassment is perceived as a prosocial emotion, while the areas that are the most involved are the anterior cingulate cortex, anterior insula, and medial prefrontal cortex.

Neurodevelopmental disorders such as autism spectrum disorder (ASD) and psychiatric disorders, for example, schizophrenia (SCZ) represent a large spectrum of disorders that manifest through cognitive and behavioural problems. ASD and SCZ are both highly heritable, and some phenotypic similarities between ASD and SCZ have sparked an interest in understanding their genetic commonalities. The genetics of both disorders exhibit significant heterogeneity. Developments in genomics and systems biology, continually increases people’s understanding of these disorders. Recently, pathogenic genetic variants in the regulatory factor X (RFX) family of transcription factors have been identified in a number of ASD cases. In this thesis, common genetic variants and expression patterns of genes identified to have a conserved promotor X-Box motif region, a binding site of RFX factors, are studied. Significant common variants identified through expression quantitative trait loci (eQTLs) and genome wide association studies (GWAS) are mapped to the regulatory regions of these genes and analysed for putative enrichment. In addition, single-cell RNA sequencing data is utilised to examine enrichment of cell types having high X-Box gene expression in the developing human cortex. Through the study, genes that have eQTLs or SNPs in the genomic regulatory regions of the X-Box genes have been identified. While there were no eQTLs or GWAS SNPs in the X-Box motifs, in the X-Box promoter regions some common variants were found. By hypergeometric distribution testing and the subsequent p-values obtained, all of these distributions are statistically under-enriched. Further, major cell types in the cortical region with increased expression of the X-Box genes and most expressed genes among these enriched cell types have been identified. Among the 11 cell types seven were found to be enriched for X-Box genes and many of the most expressed genes in these cell-types were similar. A further study into the cell types and genes identified, along with additional systems biological data analysis, could reveal a larger list of X-Box genes involved in ASD and SCZ and the specific roles of these genes.

Induced pluripotent stem cells (iPSCs) can self-renew and differentiate into many other cell types. IPSCs are derived from somatic cells, and upon reprogramming, they share an expression profile similar to embryonic stem cells (ESCs). Among their many applications, iPSCs are an advantageous tool for disease modelling, offering an accurate system to study human molecular networks associated with specific phenotypes. Moreover, progress in genome editing technologies improved the possibilities for investigation of genotype-phenotype relationship for diseases characterized by defined genetic variants. Indeed, CRISPR/Cas9 edited iPSCs lines from healthy donors offer the possibility to investigate molecular networks with comparison to an isogenic control line. Furthermore, the ability of iPSCs to differentiate into neural cells, makes them a good model for studying neurodevelopmental diseases (NDDs). NDDs are characterized by heterogenous genetics and phenotypes. Heterozygous gene variants in the alpha 1 subunit of the sodium-voltage gated channel 1.1 (SCN1A) and in Neurochondrin (NCDN) have been associated with epilepsy. While many variants defining NDDs are associated with genes of transcriptional networks, e.g. the zinc-finger E-box binding homeobox 2 transcription factor (ZEB2) or the RPB1 subunit of RNA polymerase II complex (POLR2A). Although published animal model systems are available, there is a lack of human derived systems to investigate the gene function in disrupted molecular networks in NDDs. In this project, IPSCs deficient for SCN1A, NCDN, ZEB2 and POLR2A were generated using CRISPR/Cas9. To further evaluate the quality of the cell lines as iPSCs model, a POLR2A knock down (K.D.) line carrying a 4 bp insertion and a ZEB2 knock out (K.O.) line carrying a 790 deletion were characterized. Pluripotency and differentiation potential were confirmed by flow cytometry analysis, immunostaining, and qPCR. Both lines maintained genome integrity and editing in the top predicted off targets was excluded with PCR and Sanger sequencing screening. Furthermore, ZEB2 is involved in induction of neural crest cells (NCC); ZEB2 deficient line and the control behave similarly after a week of NCC differentiation. In contrast, POLR2A variants suggest slowing of transcription compared to the wild-type, therefore rate of transcription was measured performing an activity assay. No relevant differences between POLR2A K.D. and control line were observed in transcription rate of early pre-mRNA.

Adolescence is a unique period of development. This life phase seems to entail being sensitive to aversive and social cues. However, adolescents' performances have been seen as equivalent to that of adults in nonemotional contexts. For this reason, questions remain regarding adolescents’ sensitivity to, and cognitive regulation of, emotional content. In line with this, the following paper aimed to provide a literature review of the successful use of an emotion regulation (ER) strategy, known as reappraisal, and its normative development during adolescence. Specifically, the main focus ofthis paper was to review studies investigating age differences of adolescents' reappraisal capacity in association with related functional activity, as measured by functional magnetic resonance imaging (fMRI). Reappraisal, i.e., to rethink the appraisal of an emotionally eliciting stimulus as to change one’s emotional response, is a well-studied psychological phenomenon. Research of reappraisal ability has mainly been studied on adults when viewing aversive images. Therefore, such findings in the field that are of relevance for the more in-depth review a represented. The studies reviewed suggest that reappraisal may account more for age differences in emotional responding than emotional reactivity. Generally, reappraisal ability shows increased success with increasing age. The paper ends with a discussion of results and limitations within the field, such as regarding the various terminology and instructions used for reappraisal tactics.

Studies have shown that aberrant activity in some brain regions involved in the pathology of OCD overlaps similarly with individuals with addiction disorders. The reduced anxiety following a compulsion together with findings of diminished activation in the striatum during reward anticipation proposes a view of OCD being a behavior addiction. To investigate if there are consistent results across studies that support this view a systematic search of the literature was conducted. The keywords in the final search string used were: Obsessive-compulsive disorder, OCD, reward, risk, functional MRI, MRI, fMRI. Databases used for the search were Web of Science and PubMed. The inclusion criteria were studies that compared the neural activity during the anticipation phase of reward between OCD patients and healthy controls. The intervention and brain imaging used in the included studies were the monetary incentive delay task and fMRI. The main data extracted were the alterations in the striatum. Four studies were included in this review with inconsistent results. Three studies did not find any significant difference between OCD and healthy controls and therefore the findings in principle did not support the view of OCD being a behavior addiction. However, differences in study design between studies could be an explanation for the conflicting findings.

Trait mindfulness refers to the tendency of being mindful in everyday life. Individuals characterized with high trait mindfulness have reported high subjective wellbeing and are less prone to depression and stress. The aim with this systematic review was to investigate the neural correlates of trait mindfulness. Also, to compare the neural correlates underlying trait mindfulness with those related to mindfulness practices. A systematic search, screening and selection was conducted, resulting in twelve articles included for data extraction and discussion. All studies investigated resting state brain activity or brain structure, measured by fMRI or MRI, in relation to individual scores in trait mindfulness measures. Trait mindfulness was characterized by reduced connectivity within the DMN (between the PCC, the medial PFC, the STG and the thalamus e.g.) and increased functional connectivity between the insula and the ACC within the SN. Further, decreased functional connectivity between the DMN and the SN was observed. No consistent structural correlates characterizing trait mindfulness were reported. Reduced connectivity within the DMN is thought to associate with reduced vulnerability to rumination and depression. Increased connectivity within the SN has been linked to enhanced body awareness and interoception. Decreased functional connectivity between the DMN and the SN has been suggested to facilitate enhanced attention. Trait mindfulness appears to share some neural characteristics with those linked to mindfulness practices: weaker functional connectivity within the DMN, increased involvement of the insula and the ACC within the SN, and weaker connectivity between the DMN and the SN.

Depression and anxiety are two of the most common psychiatric disorders and leading causes of disability. Antidepressants and anxiolytics, though revolutionary, do not treat all those suffering from these diseases satisfactorily. Psychedelics are currently under investigation as remedies for several ailments, including depression and anxiety. One classical psychedelic, Ayahuasca, is a concoction of the plants Banisteriopsis caapi and Psychotria viridis and has historically been used by Amazonian natives for therapeutic and ritual purposes. The brew contains monoamine oxidase-A inhibitors (MAOI) and N,N-dimethyltryptamine (DMT), producing an altered state of consciousness characterized by visions and introspection. In this systematic review, I aimed to determine the antidepressant and anxiolytic effects of Ayahuasca. Sixteen articles out of 687 hits on electronic databases (Web of Science, Scopus, and PubMed) were finally included after closer examination. The studies range in quality and are performed on healthy volunteers and volunteers with self-reported depression or anxiety and patients suffering from treatment-resistant and major depression. Ayahuasca seems to be well tolerated and safe to administer and consistently produce antidepressant and anxiolytic effects in the studies. However, the description of the sometimes arbitrary results vary, and higher-quality research is needed before we can be certain of Ayahuasca as a remedy.

A big part of the female population experience pregnancy and giving birth. Evidence from animal studies indicates numerous adaptations in the brain throughout pregnancy and the postpartum period. The effects on the human brain are not as well studied, which is problematic due to the complexity of comparing species. Therefore, a systematic review of existing research regarding the structural and functional brain changes in humans, due to pregnancy and early postpartum period, was conducted. Databases used for the search were PubMed, Scopus, and Web of Science. The literature search and screening process resulted in eight studies included for data extraction. The included studies have a wide range of methods, where four studies used magnetic resonance imaging (MRI), two functional magnetic resonance imaging (fMRI), one near infrared spectroscopy (NIRS), and one study used electroencephalography (EEG) and MRI. The result indicates that the female brain is smaller and anatomically older during pregnancy but quickly restores after delivery. It also showed that normal changes in brain function occur during pregnancy and early postpartum period. The main limitation in this review were the lack of studies, and their heterogeneity of neuroimaging techniques, study design, and time of measurement. More studies during pregnancy or shortly after delivery are needed to fully understand the effects pregnancy has on the human female brain.

Depression and anxiety are two of the world’s most common neuropsychiatric conditions. There has been some success in treating depression and anxiety by using classic psychedelic drugs to cause positive changes in psychological well-being. Depression and anxiety are often correlated to self-rumination and a heightened sense of self, making sufferers unable to withdraw from repetitive negative self-referenced thought patterns. Some researchers hypothesize that the therapeutic effects of psychedelics come from their acute subjective effects, specifically ego-dissolution. This systematic review aimed to investigate what clinical studies can support this hypothesis. By reviewing five studies that examined this correlation, this review found that the majority of the studies could present a moderate correlation. This suggests a negative correlation between the degree of ego-dissolution and the therapeutic improvements in disorders with a heightened sense of self.

Compassion is an affective state and comprises recognition of the suffering of others and a motivation to help them. Studies have indicated that compassion is trainable and compassion training based on contemplative practice has beneficial effects on well-being. The primary aim of this thesis was to conduct a systematic review on the functional and structural neural effects of compassion training in healthy adults. The secondary aim was to review the psychological or behavioral changes after compassion training in the reviewed articles. Eight articles employing compassion meditation or loving-kindness meditation, and applying the same definition of compassion, were reviewed. The neural effects of compassion training were diverse, but changes in the activity of the medial orbitofrontal cortex (mOFC), the amygdala, and reward-related areas were the most consistent outcomes. Also, compassion training resulted in increased positive affect and feelings of compassion, decreased depression scores, and more charitable donations (i.e., prosociality). The findings of this systematic review suggest that compassion training engages a broader neural network than previous studies have indicated and is a strategy that may lead to improved well-being andprosocial behavior.