Individuals with borderline personality disorder (BPD) experience emotional instability and have a high suicide rate. Treatment for BPD includes psychotherapy and adaptive emotion regulation strategies, which include cognitive reappraisal. Previous systematic reviews indicate that abnormal brain patterns may cause emotional instability in BPD individuals. To further explore this, this review collected articles that examined neural activity using fMRI during cognitive reappraisal in subjects with BPD and healthy controls. We identified four relevant articles through a search of Web of Science and PubMed. The articles included conflicting results in both participant groups regarding increased or decreased activity during cognitive reappraisal applying either reinterpretation or distancing. The affected brain regions were the following: lateral and ventrolateral prefrontal cortex, left middle temporal gyrus, and superior temporal gyri. Three of the articles reported consistent results of activity in the dorsolateral prefrontal cortex during downregulation, two in all participants and one only in the healthy control group. However, no significant group differences were found in this region during cognitive reappraisal. The discussion includes limitations regarding the comparability of the included studies, such as the method of eliciting negative affect, the use of written or verbal instructions, and the cognitive reappraisal strategy applied. Further research is necessary to better understand the involvement of distinct brain regions in cognitive reappraisal and BPD, as well as to establish more standardized research methods. These efforts can offer comprehensive insights into the neural mechanisms underlying cognitive reappraisal in individuals with BPD.

Individuals exhibit different reactions to stress, both between individuals and within individuals at different time points. A person’s current emotional state is one of the primary factors that influences how they handle a stressful situation. Someone who is feelingdepressed or anxious may not cope with stress as well as when they are feeling at peace. Another factor that impacts an individual’s ability to cope with stress is being, or at least feeling, in control of the stressful situation. Uncontrollable stress can cause greater emotional disruption and negatively affect behaviour and motivation. Stress-related psychiatric disorders are common today, and research in this field is essential to help individuals improve their stress-coping abilities. In this study, we measured physiological stress responses (heart rate variability and skin conductance) while participants performed a widelyused stress induction task and a novel stress induction task that systematically varied controllability. Before the tasks, participants reported their baseline levels of depression, anxiety, and stress. Our goal was to investigate if negative emotional states predicted the physiological stress response and if stress reactivity to the well-established task was related to stress reactivity when facing an uncontrollable stressor. We hypothesised that individuals who experience more negative emotional states would exhibit a stronger physiological stress response to both tasks. The data we obtained from 61 participants indicated that participants reacted differently to the two stress tasks, but we did not observe any significant impact of depression, anxiety, or stress levels.

A virtual environment can offer a highly immersive experience with a feeling of presence similar to the physical world. Nevertheless, it still lacks several multisensory and emotional properties to fully substitute or replicate the physical world's richness and complexity. Accordingly, this study examines how multisensory integration relates to the immersive and restorative outcomes in an artificial nature paradigm. Our experiment collected behavioral and physiological data through self-report questionnaires and heart rate variability assessment from 30 participants. Notably, due to unforeseen technicalities, the heart rate data was not analyzed. Participants were divided into three conditions comparing audio and visual stimuli.Two conditions were unisensory (visual and auditory), and one was multisensory (audio-visual). We found no statistically significant difference in the level of immersion between unisensory and multisensory conditions, supporting the inconsistency and need formore research regarding the relationship between multisensory integration and immersion. Inrelation to restorativeness, we found a significant difference between audio-visual and audioconditions. Additionally, the medium to strong effect size indicates that visual stimuli substantially influence restorative effects more than audio stimuli. Collectively, in line with previous research, we observed a positive effect on restorativeness from spending time in artificial nature. Despite some limitations, our findings provide guidance for future researchers and contribute to the understanding of immersive multisensory VR experiences and their potential to promote mental rejuvenation and optimize restoration.

Psychopathy is a frequently reported personality trait among violent offenders, and psychopaths have a higher rate of recidivism than inmates without psychopathic features. This systematic review aimed to investigate whether structural brain differences, measured with magnetic resonance imaging, are observed in violent offenders with psychopathy compared to violent offenders without psychopathy or healthy non-violent controls. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search utilised the academic databases Web of Science and Medline EBSCO and included original peer-reviewed articles written in English and published between 2013 and 2023. Seven articles fulfilling the inclusion criteria were selected for the review. The findings indicated that there are structural differences between violent psychopaths compared to non-violent psychopaths and healthy controls, such as reduced grey matter volume in the prefrontal cortical areas, posterior cingulate cortex and precuneus, and striatal and limbic regions. Further, the degree of structural brain differences in psychopaths correlated with the degree of psychopathic traits. The structural differences found in the brains of violent psychopaths can provide insight into the neurobiological basis and neural mechanisms of psychopathy and elucidate how changes in brain morphology relate to antisocial behaviour and psychopathic personality traits. In addition, the evidence of structural abnormalities in the brain of psychopaths may help develop targeted treatments that could reduce the risk of psychopathic individuals turning to crime and violence or committing repeated violent crimes.

The phenomenal experience of our visual perception, what it is like to be in that state, is something that we might take for granted. However, looking closer at the neural correlates of visual processing in relation to phenomenal experience we recognize that it is a complex issue. Whether our subjective experience of our visual representation of the world is attached to cognitive functions, like working memory and attention, or whether some sort of richness overflows such functions, is an ongoing debate within cognitive neuroscience. Advocates for overflow argue that phenomenal experience is the result of activity in posterior occipito-temporo-parietal areas and is independent of attention, while those within the non-overflow position mean that for phenomenal awareness to arise activity in higher-level areas like the prefrontal lobe is needed. Finding evidence for unattended visual phenomenal consciousness without access consciousness would support the overflow position since it could indicate phenomenal experience as independent of attention. In addition to this debate, researchers need to keep in mind what methods are being used to measure phenomenal experience, since several biases potentially follow studies using introspective measures. Through this systematic review, a search string provided empirical studies based on fMRI that investigated unconscious and conscious visual processing. The results of this review show little or weak evidence for unattended visual phenomenal consciousness and do not seem to overflow cognitive functions.

Science has recently begun showing interest in the different mechanisms of the psychopathic brain, and current scientific research points to deficits in the structural and functional brain regions of psychopaths. Psychopathy is a disorder distinguished by its persistent antisocial behavior, emotional callousness, grandiose self-estimation, and lack of empathy. Further, it is also a disorder which is hard to classify. Notably, the Hare-Psychopathy Checklist-Revised (PCL-R) is the most common clinical rating scale used to diagnose psychopaths. This current systematic review aims to scrutinize literature that reviews psychopathy, delving into articles on neural correlates of emotion recognition of psychopaths. By using the PRISMA guidelines, this systematic research was conducted through, MEDLINE EBSCO, Web of Science, PubMed, and Scopus. Through predisposed eligibility criteria, articles were chosen and reviewed. All selected articles found a significant result where psychopaths performed poorly on emotion recognition and important areas such as the prefrontal cortex and amygdala could be seen to perform worse. Notably, due to different test methods, one is unable to properly evaluate the results between the studies. Therefore, upcoming studies need to shed light on performing the same tests to provide stronger and equal evidence. This systematic review was done to shed better light on the disorder.

Anxiety is a high-prevalence disorder, and it is often treated by medication which can be costly, has side effects, and is not available for everyone in need. Mindfulness-based interventions (MBIs) such as mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT) are great alternatives to treat anxiety. Both MBIs are not only more accessible but have no side effects as well. To establish whether MBIs can become a main treatment for anxiety, the associated neural correlates and changes should be investigated further. The aim of this systematic review is to investigate whether neural correlates of MBIs are mainly caused by emotional or attentional neural mechanisms, or if both are involved. There were five studies selected and included according to a set of inclusion and exclusion criteria. The results suggest that MBIs are in fact effective in alleviating anxiety symptoms by enhancing both emotion and attention regulation. However, several of the included studies came with limitations such as having no significance in p-values, no control groups, and small samples. Thus, further research is needed to draw a conclusion on whether MBIs are the best alternative for the alleviation and treatment of anxiety.

Stress is an ongoing and increasing problem at a societal and individual level. This systematic review aims to evaluate which effects breathwork has on stress in a healthy population. A literature search was done on Scopus, and Web of Science for peer-reviewed, published, and original research. In the search process, it was decided to include psychological and physiological assessments due to the narrow topic. Threestudies met the inclusion criteria and were included in this review. The outcome measurements included were heart-rate variability (HRV) which measures the activity in the autonomic nervous system (ANS) and salivary cortisol to measure cortisol as a biomarker of psychological stress, as well as the questionnaires PSS, PANAS, and STAI. There are many different breathwork techniques, in this review the focus is oncontrolled, slow deep breathing techniques e.g. diaphragmatic breathing, resonance breathing, and cyclic sighing. All three studies showed significant improvement in stress in the breathing groups. These findings suggest that breathwork can be valuable in reducing stress in healthy individuals. Furthermore, more research is needed before conclusions on the general population can be drawn.

Purpose: Arterial stiffening poses an increased risk of cerebrovascular diseases, cognitive impairments, and even dementia as cardiac pulsations reach further into the brain causing white matter hyperintensities and microbleeds. Therefore it is of interest to obtain methods to estimate and map cardiac related pulsatility in the brain. Improvements of functional magnetic resonance imaging (fMRI) sequences is potentially allowing detection of rapid physiological processes in the echo-planar imaging (EPI) signal in the brainthrough a higher sampling rate. Specifically in this thesis, estimation and localization of cardiac pulsation and respiration is conducted through analysis of resting state data obtained with a multiband EPI sequence that permits whole brain imaging at a shorter repetition time (TR) than conventional EPI. The origin of these physiological signals are likely a mixture of inflow and compartment volume shifts during the cardiac- and respiratory cycles. As the amount of physiologically related signal in the multiband sequence used at the Biomedical Engineering Dept. R&D, Umeå University Hospital is unknown, the aim of this project is to find and map cardiac pulsatility and respiration for future research. Methods: Multiband fMRI data from 8 subjects was used, collected in a 3 Tesla scanner using a 32-channel head coil. The physiological signals were estimated through an algorithm that was developed to down-sample and temporally shift copies of simultaneous recordings of pulse and respiration. These signals were obtained using the scanner’s built-in pulse oximeter and a respiration belt. The shifted copies were voxel-wise, and slice by slice, correlated to the fMRI data using Pearson correlation. The time shift yielding maximum mean correlation within the brain was, for each slice, used to create statistical maps for significant voxels to show the localization and magnitude of correlation for cardiac pulsation andrespiration. Results: Many voxels around and nearby larger vessels and ventricles were highly correlated with the down-sampled, time shifted signals of the cardiac pulsation for all subjects. The cardiac pulsation maps resembled cerebral vasculature and were mostly localized around the Circle of Willis, brainstem, and the ventricles. Respiration signal was also highly correlated, and spatially located at the sides of the brain although mostly concentrated at the parietal- and occipital lobes. Conclusion: The results demonstrated that many voxels in the brain were highly correlated with cardiac pulsation and respiration using multiband EPI, and the statistical maps revealed distinct patterns for both of the physiological signals. This method and results for mapping cardiac related pulsatility, and respiration could be used for future research in order to better understand cerebral diseases and impairments, and alsoto improve fMRI filtering. Keywords: Arterial stiffness, Functional magnetic resonance imaging, Resting state, Multiband, CardiacPulsation, Respiration, Correlation analysis / Syfte: Arteriell förstyvning medför en ökad risk för cerebrovaskulära sjukdomar, kognitiva störningar och till och med demens då hjärtpulsationer når längre in i hjärnan orsakar vit materia hyperintensiteter och mikroblödningar. Av detta skäl är det därför av intresse att ta fram metoder för att estimera och kartlägga hjärtrelaterad pulsationer i hjärnan. Förbättringar av funktionella magnetresonanstomografi (fMRI) sekvenser kan möjliggöra detektering av snabba fysiologiska processer i den eko-planära (EPI) signalen i hjärnan genom en högre samplingsfrekvens. Specifikt i denna uppsats, utförs en skattning och lokalisering av hjärtpulsation och respiration genom analys av ’resting state’ data erhållet av en multiband-EPI sekvens som tillåter bildgivning av hela hjärnan med en kortare repetitionstid (TR) än konventionell EPI. Ursprunget avdessa fysiologiska signaler är sannolikt från en blandning av flöde- och volymsförändringar under hjärt- och respirationscyklerna. Då mängden av fysiologiskt relaterad signaler i multiband sekvensen, som används på Biomedicinska avdelningen, FoU Umeå Universitetssjukhust, är okänd så är målet med projektet att hitta och kartlägga hjärtpulsation och respiration för framtida forskning. Metod: Multiband fMRI data från 8 personer användes, insamlade från en 3 Tesla scanner med en 32-kanals huvudspole. De fysiologiska signalerna uppskattades genom en algoritm som utveckades för att sampla ned och tidsförskjuta kopior av simultant tagna signaler av puls och respiration. Dessa signaler samlades in med skannerns inbyggda pulsoximeter och andningsband. De förskjutna kopiorna var voxelvis, snitt för snitt, korrelerade med fMRI datat med användning av Pearson-korrelation. Det tidsskift somför varje snitt resulterade i maximal medelkorrelation i hjärnan användes för att skapa statistiska kartor, med endast signifikanta voxlar, för att visa var och hur mycket korrelation av hjärtpulsation och respiration som finns. Resultat: Många voxlar runt och nära större kärl och ventriklar var för alla personer starkt korrelerade medde samtidigt tagna, och tidsförskjutna signalerna av hjärtpulsation. Pulsationskartorna liknade cerebral vaskulatur och var mestadels lokaliserade kring Willis ring, hjärnstammen och ventriklar. Respirationssignalen var även starkt korrelerad och lokaliserad på sidorna av hjärnan, mestadels koncentrerat vid parietal- och occipital loberna. Slutsats: Resultaten visade att många voxlar i hjärnan var starkt korrelerade med hjärtpulsation och respiration vid användning av multiband EPI, och de statistiska kartorna avslöjade distinkta mönster för de båda fysiologiska signalerna. Den framtagna metoden och dess resultat för kartläggning av hjärtrelaterade pulsationer och respiration kan användas i framtida forskning i syfte att bättre förstå cerebrala sjukdomar och nedsättning, även för att förbättre fMRI filtrering. Nyckelord: Arteriell förstyvning, Funktionell magnetresonanstomografi, Resting state, Multiband, Hjärtpulsation, Andning, Korrelationsanalys

Our genome operates by sending instructions, conveyed by mRNA, for the manufacture of proteins from chromosomal DNA in the nucleus of the cell to the protein synthesizing machinery in the cytoplasm. Alternative splicing is a natural process in which a single gene can encode multiple related proteins. During RNA splicing, introns are selectively removed resulting in alternatively spliced gene products. Alternatively spliced protein products can have very different biological effects, such that one protein isoform is disease-related while another isoform is desirable. Splice switching opens the door to new drug targets, and antisense oligonucleotides (asONs), designed to switch splicing, are effective drug candidates. Cellular uptake of oligonucleotides(ONs) is poor, therefore utilization of cell-penetrating peptides (CPPs), well recognized for intracellular cargo delivery, is a promising approach to overcome this essential issue. Most CPPs are internalized by endocytosis, although the mechanisms involved remain controversial. Here, evaluation of CPP-mediated ON delivery over cellular membranes has been performed. A protocol that allows for convenient assessment of CPP-mediated cellular uptake and characterization of corresponding internalization routes is established. The protocol is based on both fluorometric uptake measurements and a functional splice-switching assay, which in itself is based on biological activity of conveyed ONs. Additionally, splice switching ONs (SSOs) have been optimized for high efficiency and specificity. Data suggest that SSO activity is improved for chimeric phosphorothioate SSOs containing locked nucleic acid (LNA) monomers. It is striking that the LNA monomers in such chimeric constructs give rise to low mismatch discrimination of target pre-mRNA, which highlight the necessity to optimize sequences to minimize risk for off-target effects. The results are important for up-coming work aimed at developing compounds consisting of peptides and novel synthetic nucleic acids, making these entities winning allies in the competition to develop therapeutics regulating protein expression patterns.