Browsing by master's degree program "Master 's Programme in Neuroscience"

Each year many new-borns are at risk for long-term developmental deficits due to adverse perinatal events. Early gross motor abilities have been shown to link with cognitive development and studying infant motor behaviour may provide means to assess global neurodevelopment. This thesis aims to explore a potential association between early gross motor abilities recorded at infancy with a multi-sensor wearable jumpsuit MAIJU and later neurocognitive development assessed at two years of age. The study sample (N=26) consisted of healthy full-term infants and those with prematurity or perinatal asphyxia. Spontaneous motor activity was recorded at home with the jumpsuit. Machine learning methods were used to quantitate the time infants spent in different postures and estimate the maturity of their motor abilities, which were compared to cognitive development at two years of age with correlational- and regression analyses. There was a positive trend between early motor abilities and later cognitive development. Specifically, standing posture explained the association, such that infants who spent more time standing had better cognitive abilities at two years of age. Standing may support cognitive development by increasing opportunities for visual and manual exploration and learning. Shared neuronal circuitries for motor and cognitive functions and faster neuronal maturation may also underlie the association. The current study supports the creation of future studies with larger sample sizes to establish the potential for the use of postural and movement information obtained from wearable jumpsuit MAIJU to assess the variability of neurocognitive development of at risk and typical infants with potential goal to identify future cognitive deficits at early stage.

White matter (WM) structural connectivity alterations have been linked to depression. This study aimed to identify structural connectivity metrics associated with Major depressive disorder (MDD) and predictive of different symptom phenotypes. The study sample included N=29 control and N=86 subjects with MDD who underwent a clinical interview, Mini-International Neuropsychiatric Interview (MINI), and assessment of depression symptoms severity. Using a 3T MRI scanner, diffusion tensor imaging (DTI) was employed to capture WM connectivity markers at baseline. While no distinct differences between control and MDD groups were observed at the whole-brain network level, significant alterations were evident at the node level. Clinical group demonstrated enhanced connectivity, particularly in the DefaultB and LimbicB subsystems, as evidenced by measures such as eigenvector centrality. Furthermore, notable differences were observed in clustering coefficient and local efficiency, predominantly in DefaultB, LimbicB, and VisPeri networks, with MDD patients showing higher connectivity. Analysis of the association between WM structural connectivity measures, both global (e.g. global efficiency) and local (e.g. clustering coefficient) with MDD symptom scores and related symptoms, revealed no significant correlation at the whole-brain level, both at baseline and post-intervention. Distinct patterns were identified when evaluating node-level metrics averaged across networks, which together with group differences, point to MDD patients exhibiting characteristics consistent with regular networks. Hierarchical clustering based on standardized baseline DTI structural connectivity within the clinical cohort revealed three distinct clusters of MDD patients, with the first cluster exhibiting a higher WHO-5 score, indicating a potential association with better well-being. These findings provide insight into MDD-specific brain regions’ structural alterations and underscore the heterogeneity of depression symptom profiles. Further research is needed, including a higher sample size and control for confounding factors.

Women have exhibited higher levels of math anxiety (MA) compared to men. Despite the relationship between MA and sex differences being topic of interest for over twenty years, the focal point has mostly been on the psychological causes. This review investigates the biological underpinnings of the social phobia and identifies numerous possible correlates which could inform future efforts to support students experiencing math anxiety and encourage more females to pursue STEM related careers. Articles that investigated sex differences in the context of MA were selected for the study using PRISMA guidelines. Females were found to experience higher levels of math anxiety compared to males. Age was shown to influence the prevalence of MA between sexes, with sex differences in MA being more infrequent in children and increasing towards adulthood. The findings suggest that a diverse set of biological sex differences related to to brain function, cognition and sex hormones can, in part, explain the higher prevalence of MA among females and age-related deviations. By shedding light on possible biological factors contributing to sex differences in MA, this review represents a valuable step toward a more comprehensive understanding of this complex issue.

Faculty: Faculty of Biological and Environmental Sciences Degree programme: Master’s Programme in Neuroscience Study track: Cell and Systems Physiology Author: Mélina GUILLON Title: Inflammatory activation of Macrophages by Triglyceride-Rich Lipoproteins in Atherosclerosis Level: Master’s thesis Month and year: August 2023 Number of pages: 38 Keywords: Atherosclerosis, Inflammation, Triglycerides-Rich Lipoproteins, Emulsion Particles Supervisor or supervisors: Dr. Katariina Öörni Where deposited: Helsinki University Library Additional information: Background: Inflammation is a key factor in atherosclerotic cardiovascular disease (ASCVD) and is present at all phases. It has been shown that reducing inflammation by blocking cytokine pathways diminishes the risk of stroke and myocardial infarction. Despite the well-established linked between lipoproteins and atherosclerosis, little is known on the specific effect of lipids on inflammation. In this study, we investigated the impact of triglycerides-rich lipoproteins’ (TRLs) lipids on inflammation in the context of atherosclerosis. Methods: TRLs were isolated and purified from pooled plasma of healthy volunteers, and emulsion particles (EPs) generated by sonication using lipids extracted from TRLs. TRLs and EPs were characterized in size, triglycerides, and cholesterol content. THP-1 cells were treated with EPs, TRLs, and modified EPs (oxidation, vortexed, and lipolysis with PLA2), and the release of pro-inflammatory cytokines (IL-1β and TNF-α) was detected with ELISA. Results: EPs were successfully synthesized by sonication using an ultrasonic probe. EPs induced cytokine secretion from THP-1 cells (N=4). Modified EPs (Oxidized EPs, vortexed EPs, and PLA2-treated EPs) did not increase cytokine secretion (N=4). Conclusion: Our findings suggest that TRLs’ lipids contribute to inflammation and that TRLs may play a crucial role in the pathogenesis and pathophysiology of ASCVD. Inflammatory properties of TRLs should be extensively investigated in the future for the development of preventive and curative strategies.

Goal-directed behavior is reliant on the ability to choose correct actions to perform given the context of the situation while minimizing the interfering effect of goal-irrelevant stimuli. The ability to suppress inappropriate responses is called response inhibition. It can be seen as a higher order cognitive function which is one of the cornerstones for adaptive behavior in ever changing environment. Neural oscillations have been previously used to study at the neuronal processes underlying cognitive processes such as response inhibition. Neural oscillations are rhythmic fluctuation in the excitability of a neuron or a group of neurons. These temporal windows of excitability are thought to underlie efficient communication by changing the efficacy of the synaptic transmissions between neurons/group of neurons. Although, a lot has been uncovered about the different oscillations and their possible role in response inhibition, very little is known how the spectral content (power of a frequency) adapts across as the animal is learning to suppress their responses to new novel stimuli. This kind of learning associated spectral content adaptations has been observed previously in humans during motor learning for example. In the current study we aimed to look how spectral content adapts as the animals learn to suppress their responses to novel stimuli. We used head fixed rats on a treadmill that were trained to perform Go/NoGo task. Each rat performed 1-4 learning scenarios during which the “rules” for Go/NoGo task changes in an attentional set-shifting paradigm. We measured EEG from most of the rat’s cortex. EEG was measured from the point where the rat was first introduced to these novel stimuli until the rat had learned the new stimulus-response contingences. This EEG was divided into learning stages and the power spectrum was calculated for each of them. We observed power peaks centered around 1Hz, 2Hz, 4Hz, 8Hz and 11Hz across learning stages. However further analyses comparing average power across learning stages showed that these changes were not statistically significant. Thus, we did not observe gradual changes in power while rats were learning to suppress their responses to novel stimuli.

Introduction: Oxidative stress occurs in cells when reactive oxygen species are generated as a by-product of oxygen metabolism and start to accumulate excessively. While extensive oxidative stress is highly detrimental to the cells, trophic factors help them survive. Trophic factor MANF has interested especially Parkinson’s disease researchers, but recent findings suggest that MANF plays a role in many diseases, also ones with an early childhood-onset. For this reason, it is important to investigate MANF function in different cell types. We have studied how MANF-knockout human embryonic stem cells react to oxidative stress compared to wild-type human embryonic stem cells, by exposing the cells to hydrogen peroxide and ethanol. Results: MANF-knockout human embryonic stem cells were more sensitive to oxidative stress than wild-type cells, but the variation between measurements was remarkable and the differences were statistically insignificant. We found that a transcription factor of our interest localized in the cell nuclei of MANF-knockout cells upon oxidative stress exposure. Such a nuclear translocation did not occur in wild-type cells. Moreover, we found that high concentrations (>2%) of ethanol reduced the viability of cells in only four hours. Discussion: Our findings suggest that MANF-knockout human embryonic stem cells react to oxidative stress differently than wild-type cells. Additional studies are necessary to clarify whether MANF-knockout human embryonic stem cells are indeed more sensitive to oxidative stress than wild-type cells. In the future, it would be interesting to inspect whether MANF protects human embryonic stem cells when the cells are exposed to physiologically relevant ethanol concentrations for longer periods of time.

The sense of hearing is dependent on the sensory cells of the cochlea: inner and outer hair cells. The critical functional structure of these cells is the stereocilia bundle, the mechanotransduction (MET) organelle. The outer hair cells (OHCs) are highly vulnerable to environmental assaults, the effects of aging, and gene mutations. This vulnerability is thought to be mediated by challenges in maintaining intracellular calcium homeostasis. Endoplasmic reticulum (ER) stress is a form of cellular stress that was previously shown to cause hair cell impairment. A possibility is that this impairment is mediated by perturbations in calcium homeostasis. In this thesis, the aim was to find out how the OHC calcium homeostasis is affected by specific ER stress-inducing mutations and age in mouse models exhibiting progressive hearing loss. I studied OHC calcium homeostasis in Manf conditional knock-out (cKO) mice under C57BL/6 (B6) strain in which ER homeostasis-promoting protein MANF (Mesencephalic Astrocyte-derived Neurotrophic Factor) is depleted in cochlear hair cells. Previous studies have shown that these mice develop progressive hearing loss that includes OHC loss and prominent stereocilia pathology, stereocilia fusion. By itself, the B6 mouse strain is a model of age-related hearing loss due to a Cdh23 missense mutation that is known to cause progressive hearing loss and, according to earlier evidence, may be a source of ER stress. I studied B6 mice at 6–9 months of age and Manf cKO mice at 2 months of age to comparatively examine changes to OHC calcium homeostasis that may correlate with the changes in the stereocilia bundle morphology and with hearing loss. I studied hearing function by auditory brainstem recordings in vivo. I estimated the functionality of MET channels in OHCs by FM1-43 uptake. I used immunofluorescence microscopy to study subcellular expression of key calcium-buffering and calcium-extrusion proteins in OHCs. I used a novel super-resolution imaging technique, expansion microscopy (ExM), to study stereocilia bundle morphology. OHCs of Manf cKO mice showed changes in calcium homeostasis in all the studied aspects: (1) FM1-43 uptake through MET channels was reduced, (2) the expression of the calcium extrusion pump PMCA2 and its obligate partner, the cell adhesion protein neuroplastin, was decreased, (3) and the expression of calcium-buffering protein oncomodulin was increased. All this data indicated OHC calcium dyshomeostasis. These molecular changes were consistent with the hair bundle pathology—stereocilia fusion—revealed by phalloidin staining of the actin-rich core of the stereocilia followed by ExM imaging. OHCs of 6–9-month-old B6 mice exhibited reduced FM1-43 uptake, yet not to the extent seen in cKO mice, and there were no changes in PMCA2 and neuroplastin expression and no prominent stereocilia fusion. Together, I show in this study that OHC hair bundle dysmorphology is linked with changes in calcium homeostasis in the mouse model of ER stress-induced hearing loss. This is consistent with the fact that calcium dyshomeostasis is an integral part of cellular ER stress. An intriguing, yet unanswered question is whether these changes in stereocilia bundle physiology could actually be the trigger for the death of these sensory cells.

Ympäristöön sopeutuminen on laaja käsite, joka pitää sisällään sekä pitkällä aikavälillä tapahtuvan evolutiivisen sopeutumisen että yksilöissä lyhyellä aikavälillä tapahtuvan fenotyypin sopeutumisen. Evolutiivisessa sopeutumisessa keskeisenä mekanismina toimivan luonnonvalinnan on havaittu olevan monille opiskelijoille haastava käsite ymmärtää, ja siihen tiedetään liittyvän paljon virhekäsityksiä. Kuitenkin suomalaisten opiskelijoiden virhekäsityksiä ja ymmärrystä aiheesta on tutkittu vain vähän. Tässä tutkimuksessa selvitettiin suomalaisten peruskoulun yhdeksäsluokkalaisten osaamista liittyen eläinten sopeutumiseen ja evoluution mekanismeihin. Lisäksi tutkimuksessa tarkasteltiin erilaisten tekijöiden, kuten oppikirjasarjan ja oppilaan luontoharrastuneisuuden, yhteyksiä aiheen osaamiseen. Tutkimusaineisto (N=90) kerättiin sähköisen kyselylomakkeen avulla. Tutkimukseen osallistui yhdeksäsluokkalaisia neljästä eri koulusta. Kyselylomake koostui sekä monivalintatehtävistä että avoimista kysymyksistä, ja aineisto analysoitiin kvantitatiivisia sekä kvalitatiivisia menetelmiä käyttäen. Kvantitatiivisessa analyysissä vastaajien kokonais- ja tehtäväkohtaisia pisteitä vertailtiin eri ryhmien, kuten eri sukupuolten ja eri kirjasarjoja käyttäneiden, välillä. Lisäksi tarkasteltiin mm. luontoharrastusten ja biologian arvosanan yhteyksiä kyselyssä menestymiseen. Kvalitatiivisessa analyysissä avoimen tehtävän vastauksista eriteltiin oppilaiden virhekäsityksiä luonnonvalinnasta, ja virhekäsitykset luokiteltiin vakavuuden perusteella eri tasoihin. Vain pieni osa yhdeksäsluokkalaisista menestyi evoluutiota ja sopeutumista koskevassa kyselyssä hyvin ja osasi vastata luonnonvalinnan mekanismeja koskevaan avoimeen kysymykseen tieteellisen käsityksen mukaisesti. Suurella osalla tutkittavista havaittiin vakavan tason virhekäsityksiä luonnonvalinnan mekanismeista. Luonnonvalinnan eri osa-alueista oppilaat ymmärsivät heikoiten populaation muutoksen, muuntelun alkuperän ja lajiutumisen. Fysiologiseen sopeutumiseen liittyvissä tehtävissä oppilaat suoriutuivat hieman paremmin kuin evolutiivista sopeutumista koskevissa tehtävissä. Oppilaan viimeisimmän biologian arvosanan ja kyselyssä menestymisen välillä havaittiin positiivinen riippuvuus. Tulosten perusteella opetussuunnitelman keskeiset, evoluutiota koskevat tavoitteet eivät näytä toteutuvan kuin harvojen oppilaiden kohdalla, ja siten peruskoulun evoluutio-opetusta olisi yhä syytä kehittää. Saatuja tietoja evoluution ymmärtämisen ongelmakohdista ja yleisimmistä virhekäsityksistä voidaan hyödyntää opetuksen kehittämisessä. Jatkossa olisi tärkeää kehittää evoluutio-opetukseen uusia, erilaisia opetusmenetelmiä sekä selvittää niiden toimivuutta tämän haastavan aiheen oppimisessa.

Schizophrenia (SZ) is a neurodevelopmental psychiatric disorder with high heritability. Patients with SZ commonly suffer from sleep problems of different types, some of them with potential underlying abnormalities in sleep oscillations. These changes in sleep are usually accompanied by deficits in cognitive performance. However, the relationship between sleep, cognitive performance and genetic risk factors are not well known in SZ. In this study, patients were selected from a nation-wide SUPER -cohort. Sleep and circadian rhythm of patients with SZ (n = 26) and age-matched healthy controls (n = 11) were followed for a week with actigraphy and sleep diary, combined with word-pair -memory task and polysomnography at the end of the week. The results showed that patients spend more time in lighter sleep and awake during the night than controls. As expected, patients had impaired sleep spindle density compared to controls. Additionally, patient had worse overnight memory consolidation. However, sleep spindle density was not associated with memory performance. Lastly, polygenic risk score (PRS) for long sleep, but not PRS for SZ, predicted lower spindle density in patients, which could be indirect evidence for deviated neurophysiological processes of sleep behind the observed deviations in EEG oscillations among the patients. These results show that, as compared to controls, patients with SZ demonstrate abnormalities in their sleep, which can be seen both in macro- and microstructures of sleep. Further analyses of the interplay between sleep oscillations and genetic risk factors are likely needed to link sleep problems with overnight memory consolidation.

Faculty: Faculty of Biological and Environmental Sciences Degree programme: Master’s Programme in Neuroscience Study track: Neuroscience Author: Emma-Helka Erkkilä Title: The brain physiology of stress and the effects of burnout on executive functions Level: Master’s thesis Month and year: 08/2022 Number of pages: 35 Keywords: executive functions, emotion, cognition, stress, burnout Supervisor or supervisors: Docent Kaisa Hartikainen and Lic.Med. Mia Pihlaja Where deposited: Helsinki University Library Additional information: Abstract: BACKGROUND- Burnout as a result of prolonged and excessive stress may impair higher order cognitive functions of the brain such as executive functions and their efficiency. This Master's thesis examines the effects of chronic stress on the brain, more specifically the effects of burnout on executive functions. The aim of this study was to specifically research the effects of burnout on executive and emotional functions and their interaction. The research was conducted at the Behavioral Neurology Research Unit, Tampere University Hospital as part of Sustainable Brain Health project funded by the European Social Fund. MATERIAL AND METHODS- 54 voluntary examinees of whom 51 were analyzed. The examinees were divided into two groups based on BBI-15 survey (27 suffering from burnout and 24 control subjects without burnout). The examinees performed a computer-based Executive reaction time (RT) test, during which a 64-channel electroencephalogram (EEG) was recorded. In additions all examinees received alternating transcutaneous vagus nerve stimulation (tVNS) and placebo stimulation. From the Executive RT test, we obtained objective measures reflecting the efficiency of executive functions (RT and total errors) and specific executive functions such as working memory, inhibition and attention. Additionally, the emotional stimulus included in the test enabled the assessment of the emotional functions and the interaction between emotional and executive functions. The EEG and tVNS results were not in the scope of this master’s thesis, and they will be reported later on. RESULTS- The results of this thesis are preliminary. Distinct positive correlation was observed between burnout assessment based on the BBI-15 survey and the results of the BRIEF-A self-report which measures the subjective experience of challenges in executive functions in daily life. There was no statistically significant (p<0.05) difference between the groups in RTs or errors made in the Executive function RT test. Instead, the groups differed on how the threatening emotional stimulus affected the accuracy of responses. Subjects suffering from burnout made less errors with a threatening emotional stimulus compared to a neutral stimulus and vice versa the control subjects made more errors with the threatening emotional stimulus compared to neutral. This difference was statistically significant (p=0,025). DISCUSSION- Challenges experienced in everyday executive functions were linked with burnout. However, RTs and errors in the Executive reaction time test did not correlate with the severity of the burnout nor were the self-evaluated problems in executive functions depicted in the test performance. Instead, the subjects suffering from burnout differed from the control group in how the threatening stimulus affected the accuracy of responses in the test. It is possible that the subjects suffering from burnout benefit from the increase in arousal caused by the threatening emotional stimulus which was shown as improved accuracy of responses when there was a threatening stimulus, whereas the control group's accuracy of responses was disrupted by the threatening stimulus. We speculate that if the control group’s baseline level of arousal was optimal then the threatening emotional stimulus may have increased arousal to suboptimal level causing decrease in performance. Subjectively experienced challenges in executive functions and objective changes in the interaction between emotions and the executive functions were observed in the study. In conclusion, burnout causes changes in executive functions.