The childhood eye cancer retinoblastoma originates from the retina and its development is initiated while the foetus is in the uterus. Retinoblastoma has a reported incidence of 1 in 15-18 000 live births, and approximately 90% of all patients are diagnosed before the age of 5. The occurrence of retinoblastoma is usually detected by the parents and the most frequent symptoms are leukocoria (white pupillary reflex), strabismus (squinting) or if the child complains of visual problems. Retinoblastoma is diagnosed by examination under anaesthesia and documentation by RetCam. It is treated with various cytostatic agents, or by laser. If the treatment is unsuccessful, or there is a risk that the tumour cells will spread and form metastases, the eye is removed. Previous studies have indicated that the cell type from which the tumour arises, the cell-of-origin, may be the cone photoreceptors and/or their immediate interneuron, the horizontal cells. Determining the cell-of-origin for retinoblastoma is an important goal, however, understanding the molecular mechanisms that distinguish the photoreceptors and the horizontal cells from the other retinal cells may prove just as important for understanding this disease. The aim of my project has been to develop, optimise and validate methods to label, map and target expression to photoreceptors and horizontal cells in the chicken embryonic retina. We have successfully established several methods that test the expression pattern of conserved, regulatory DNA sequences, and have performed short- and long-term expression of various genes that have been reported to be involved in cell cycle regulation and cell fate determination. One of my most important findings was that a region from the RXRγ gene allowed us to specifically target the photoreceptors and horizontal cells. Our previous knowledge, together with the newly established tools, puts us an important step closer towards understanding the development and behaviour of the retinal photoreceptors and horizontal cells, however, further studies are of course needed.

Specification of the many unique neuronal subtypes found in the nervous system depends on spatiotemporal cues and terminal selector cascades, mostly acting in sequential combinatorial codes of transcription factors (TFs) to dictate cell fate. Out of 10,000 cells in the Drosophila embryonic ventral nerve cord (VNC), only 28 cells selectively express Nplp1. The Nplp1 neurons in the Drosophila VNC can be subdivided into the thoracic ventro-lateral Tv1 and the dorsal-medial dAp neurons. Nplp1 expression in both cell subtypes is activated by the same terminal selector cascade: col > ap/eya > dimm > Nplp1. However Tv1 and dAp neurons are generated by different neuronal progenitors (neuroblasts, NB), and depend on different upstream cues to activate the cell specification cascade. The Tv1 cells are generated by NB5-6T, and in these cells the Nplp1 terminal selector cascade is triggered by spatio-temporal input provided by Antp/hth/exd/lbe/cas. Our studies identified that NB4-3 gives rise to the dAp cells and that the Nplp1 terminal selector cascade in dAp cells is activated by Kr/pdm>grn. I demonstrated how two different spatio-temporal combinations can funnel on a shared downstream terminal selector cascade to determine a highly related cell fate, in different regions of the VNC. I tested this scenario at the molecular level, by identification of cisregulatory modules (CRMs) for the main factors involved in the Nplp1 terminal selector cascade. Intriguingly, I found that col is under control of two separate CRMs, which are controlled by either Antp/hth/exd/lbe/cas in the NB5-6T lineage, and Kr/pdm/grn in the NB4-3 lineage. In addition, CRISPR deletion of the endogenous col CRMs did not result in loss of Col and Nplp1, indicating that col might be under control of more, yet unidentified CRMs. Nplp1 is expressed in one out of four cells in the thoracic Apterous cluster (Ap cluster); the Tv1 cell. The allocation of the right cell fate to each of the four Ap cluster cells, is regulated by the sub-temporal cascade including the factors Sqz/Nab/Svp, acting downstream of the temporal factor Cas. The sub-temporal factors have a repressive action on Col and Dimm, and thus on the terminal selector cascade regulating Nplp1 expression in the Tv1  cell. We demonstrated that the late and Tv1 specific expression of the early temporal factor Kr suppresses Svp in the Tv1 cell and allows for the progression of the Nplp1 cell fate specification cascade. Hence, early temporal factors involved in temporal progression of neuronal progenitors, can be re-utilized late and postmitotically to specify cell fate. It is tempting to speculate that similar mechanisms act to generate similar cell fate in different regions of the CNS, as well as the issue of sub-temporal multitasking, are common features both in Drosophila and higher organisms.

Binge eating disorder (BED) is the most prevalent of all eating disorders and is characterized by recurrent episodes of eating a large amount of food in the absence of control. There have been various kinds of research of BED, but the phenomenon remains poorly understood. This thesis reviews the results of research on BED to provide a synthetic view of the current general understanding on BED, as well as the neural correlates of the disorder and treatments. Research has so far identified several risk factors that may underlie the onset and maintenance of the disorder, such as emotion regulation deficits and body shape and weight concerns. However, neuroscientific research suggests that BED may characterize as an impulsive/compulsive disorder, with altered reward sensitivity and increased attentional biases towards food cues, as well as cognitive dysfunctions due to alterations in prefrontal, insular, and orbitofrontal cortices and the striatum. The same alterations as in addictive disorders. Genetic and animal studies have found changes in dopaminergic and opioidergic systems, which may contribute to the severities of the disorder. Research investigating neuroimaging and neuromodulation approaches as neural treatment, suggests that these are innovative tools that may modulate food-related reward processes and thereby suppress the binges. In order to predict treatment outcomes of BED, future studies need to further examine emotion regulation and the genetics of BED, the altered neurocircuitry of the disorder, as well as the role of neurotransmission networks relatedness to binge eating behavior.

Background: The five-factor model is the most prominent theory in personality science which aspire to understand the thoughts, feelings and behavior of individuals, determined by five relatively stable domains. Neuroticism, defined as a higher threat reactivity and susceptibility to negative affect, is one domain which has proven problematic for well-being, and has estimated societal costs of approximately 2.5 times that of common mental disorder per 1 million inhabitants. Problem: The neural correlates of neuroticism could supply research with a fundamental base of understanding the trait, however, due to scattered founding’s of segregated activity in brain structures relative to neuroticism, meta-analyses argue that increased understanding of global rather than local organization, could be more fruitful for the investigation. Methodology: Since neuroticism is convergent with emotional instability, two structures of interest with regards to global organization are the amygdala, crucial for emotion generation, and the prefrontal cortex (PFC), responsible for emotion interpretation and emotion regulation. Reviewing brain imaging research conducted with emphasis on integrative communication between the amygdala and the PFC in individuals with high trait neuroticism has therefore been the main objective of this thesis. Results/conclusion: According to the investigated research there is compromised structural integrity correlated with neuroticism, while the research on functional communication between the structures explored is not yet sufficiently covered to supply a satisfactory answer. Some of these neurobiological findings are in line with personality science observation in neuroticism, and could hence contribute to the investigation. However, more research is warranted in this field of neuroscience.

Stress-related psychological ill health has increased dramatically in Europe. A diagnosis equivalent to occupational burnout can be found in the Swedish version of the tenth edition of the “International Statistical Classification of Diseases and Related Health Problems" by the World Health Organization. The Swedish National Board of Health and Welfare lists treatment suggestions including a section of self-care that recommended something that could be translated to “a sensible diet” (“vettig kost”) without providing evidence for what could constitute a sensible diet. By using the hypothesis of burnout being a stress-mediated decrease in neurogenesis which in turn decrease the ability to cope with stress, this article systematically reviews the efficacy of dietary polyphenols on neurogenesis in rodents to evaluate if dietary polyphenols could constitute a part of a sensible diet for burnout patients. Dietary polyphenols significantly increased various parts of neurogenesis, in rodents subjected to stressors, in some cases demonstrating effect sizes comparable to antidepressants. Adverse effects have been observed in extremely high doses and young rodents not exposed to induced stressors with a putative high level of neurogenesis.

Finding the neural mechanisms of unconsciousness is a pursuit with significance to both the scientific study of consciousness as well as for the improvement of clinical diagnosis of patients with severe structural brain damage that has resulted in disorders of consciousness (DOC), such as coma or vegetative state . This literature review gives an account for what consciousness studies have contributed to the understanding of the neural mechanisms of unconsciousness, focusing on experiments using anesthetic agents to investigate the loss and return of consciousness. Mechanisms that frequently correlate with the loss of consciousness are modulation of the brainstem, the thalamus, and the cortex, but different anesthetic drugs act on different areas. According to a bottom-up approach unconsciousness can be induced by sleep-circuits in the brainstem, and according to a top-down approach unconsciousness can be induced by cortical and thalamocortical disruption. But the mechanisms involved during loss of consciousness are not the same as for return of consciousness, and this paper includes evidence for the mechanisms involved during the return being closer to what research should be further investigating. The mechanisms involved in return from anesthesia-induced unconsciousness resemble those mechanisms involved in recovery from DOC. Studying mechanisms of unconsciousness can further our understanding of consciousness, as well as improve the diagnosis and treatment of patients with DOC.

The time of adolescence is marked by enhanced emotional experiences and difficulties with regulating one’s emotions. One way to improve the adolescent’s ability to regulate their emotions is to let them practice mindfulness meditation. The motivational drive behind this thesis is the question of what forms of mindfulness meditation are needed to give the highest increase in their emotion regulation-abilities. One problem is that while there exist neural studies on mindfulness meditation for adults, the research field of adolescent meditation lacks them. Because neural studies are needed to adequately answer this question, and the lack of brain imaging tools for this thesis, the focus here was to conduct some groundwork for this discussion. The first aim was to investigate the neural effects of mindfulness meditation on emotion regulation in adults and the second aim was to investigate to what extent we can generalize these neural effects to adolescents. To be able to theoretical discuss the second aim, neural and psychological studies on mindfulness meditation and emotion regulation were used as a base. The studies were grouped into five sub-categories based on age group and research field and then discussed with the help of developmental studies. Adult meditators had stronger functionality in regulatory brain regions than non-meditators during meditation and during the perception of negative stimuli. The discussion about the generalization of the adult neural patterns to adolescents showed that the findings were too diverse to come to any useful conclusions. Empirical and conceptual improvements, along with neural meditation studies on adolescents, are needed to improve the research field in both age groups.

My aim for this literature review is to present and discuss a possible relationship between physical exercise and different kinds of cognitive functions. With the increasing interest on the topic, more studies have been conducted and the results from the studies have been a little ambiguous. The most part of the studies has been showing that exercise has a positive effect on cognitive functions. The evidence from the studies also says that exercise can help the brain to regulate the production of new neurons and to increase brain volume in the prefrontal and temporal areas. That can be very beneficial for elderly people with dementia, Alzheimer's disease or other cognitive declines. Evidence of exercise combined with the right nutrition can enhance cognitive performance even more but to establish this more research is needed.

Frågan om människans drivkrafter och vad som ligger bakom våra handlingar har en lång historia och ju mer man har försökt att förklara och definiera begreppet motivation desto mer komplext tycks det ha blivit. Den här uppsatsens syfte är att ge en förståelse till komplexiteten kring problematiken om begreppet motivation. Detta görs genom att belysa dess djupa rötter i filosofins och psykologins värld samt lyfta fram några av motivationsteorierna ur den omfattande breda litteraturen som skrivits om ämnet. Vidare genom att belysa vad den moderna neurovetenskapliga forskningen har tillfört i studierna om motivation. Resultatet visar på att de gamla klassiska motivationsteorierna än idag influerar på ämnet. Självbestämmandeteorin (SDT) visar på att det finns olika typer av motivation och att vi föds med tre psykologiska behov som ligger till grund för en individs intrinsiska och extrinsiska motivation. Den affektiva neurovetenskapen visar på att det finns en ömsesidig interaktion mellan kognition, affektion och beteende som baseras på djupa evolutionära emotionella rötter djupt in i det limbiska systemet. Bevis finns för att nucleus accumbens (NAc) spelar en viktig roll i val av handlingsalternativ som underlättar och effektiviserar målorienterat beteende samt har både exciterande och inhiberande funktion på beteende.

Meditation, used initially as a vehicle for self-discovery and attainment of enlightenment, is today a tool for well-being among the general public and has even found its way into the clinical milieu. Meditation is challenging term to define and the variety of meditation practices, all with their own aims, pose a problem in terms of scientific understanding. A better sense of how these practices compare will help both general public and neuroscientists. Here, two of the fundamental practices originating from Buddhist tradition, focused attention (FA) and open monitoring (OM) meditation are compared. FA meditation activates mainly right medial/lateral PFC, parts of the limbic system and ACC. These regions help with sustaining attention and monitoring goal-conflicting distractors. FA deactivates parts of the default mode network (DMN), responsible for non-task specific processes and mind wandering. OM meditation reduces pain by top-down regulation of the limbic system. OM engages left fronto-parietal and insular regions, which help with conscious access of thoughts and emotions. OM seems to affect parts of the DMN. The thalamus is involved in both practices, where it helps to relay sensory signals in accordance with the different aims of each practice. This thesis hopes to contribute to a better understanding of how two main categories of meditation compare concerning their neural correlates.