Browsing by Subject "neuroscience"

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  • Tokariev, Anton (Helsingin yliopisto, 2015)
    In humans the few months surrounding birth comprise a developmentally critical period characterised by the growth of major neuronal networks as well as their initial tuning towards more functionally mature large-scale constellations. Proper wiring in the neonatal brain, especially during the last trimester of pregnancy and the first weeks of postnatal life, relies on the brain’s endogenous activity and remains critical throughout one’s life. Structural or functional abnormalities at the stage of early network formation may result in a neurological disorder later during maturation. Functional connectivity measures based on an infant electroencephalographic (EEG) time series may be used to monitor these processes. A neonatal EEG is temporally discrete and consists of events (e.g., spontaneous activity transients (SATs)) and the intervals between them (inter-SATs). During early maturation, communication between areas of the brain may be transmitted through two distinct mechanisms: synchronisation between neuronal oscillations and event co-occurrences. In this study, we proposed a novel algorithm capable of assessing the coupling on both of these levels. Our analysis of real data from preterm neonates using the proposed algorithm demonstrated its ability to effectively detect functional connectivity disruptions caused by brain lesions. Our results also suggest that SAT synchronisation represents the dominant means through which inter-areal cooperation occurs in an immature brain. Structural disturbances of the neuronal pathways in the brain carry a frequency selective effect on the functional connectivity decreasing at the event level. Next, we used mathematical models and computational simulations combined with real EEG data to analyse the propagation of electrical neuronal activity within the neonatal head. Our results show that the conductivity of the neonatal skull is much higher than that found in adults. This leads to greater focal spread of cortical signals towards the scalp and requires high-density electrode meshes for quality monitoring of neonatal brain activity. Additionally, we show that the specific structure of the neonatal skull fontanel does not represent a special pathway for the spread of electrical activity because of the overall high conductivity of the skull. Finally, we demonstrated that the choice of EEG recording montage may strongly affect the fidelity of non-redundant neuronal information registration as well as the output of functional connectivity analysis. Our simulations suggest that high-density EEG electrode arrays combined with mathematical transformations, such as the global average or current source density (CSD), provide more spatially accurate details about the underlying cortical activity and may yield results more robust against volume conduction effects. Furthermore, we provide clear instruction regarding how to optimise recording montages for different numbers of sensors.
  • Kulashekhar, Shrikanth (2017)
    Working memory is used to maintain information for cognitive operations, and its deficits are associated with several neuropsychological disorders. Human functional magnetic resonance imaging (fMRI) f isolated key brain areas associated with the maintenance of sensory and duration information. However, the systems-level mechanisms coordinating the collective neuronal activity in these brain areas have remained elusive. It has been suggested that synchronized oscillations could regulate communication in neuronal networks and could hence serve such coordination, but their role in the maintenance of sensory and duration information has remained largely unknown. In this thesis, combined magnetoencephalography (MEG) and electroencephalography (EEG) together with minimum norm estimate (MNE) based source modelling was used to study the oscillatory dynamics underlying visual and temporal working memory. In Publication I, we developed a neuro-informatics approach to understand the anatomical and dynamic structures of network synchrony supporting visual working memory (VWM). VWM was associated with a sustained and stable inter-areal phase synchrony among frontoparietal and visual areas in alpha- (10 13 Hz), beta- (18 24 Hz), and gamma- (30 40 Hz) frequency bands. In this study, the subjects' individual behavioural VWM capacity was predicted by synchrony in a network in which the intraparietal sulcus was the most central hub. In Publication II, we characterised the oscillatory amplitude dynamics associated with the VWM maintenance. Increasing VWM load was associated with strengthened oscillation amplitudes in the occipital and occipitotemporal cortical areas, in the alpha (8 14 Hz) beta- (15 30 Hz), gamma- (30-50 Hz), and high-gamma- (50 150 Hz) frequency bands. In Publication III, we addressed the functional significance of local neuronal synchronization, as indexed by the amplitudes of cortical oscillations, in the estimation and maintenance of duration information. The estimation of durations in the seconds range was associated with stronger beta-band (14 30 Hz) oscillations in cortical regions that have earlier been associated with temporal processing. The encoding of duration information was associated with strengthened gamma- (30 120 Hz), and the retrieval and comparison with alpha-band (8 14 Hz) oscillations. Further, the maintenance of stimulus duration was associated with stronger theta- and alpha-band (5 14Hz) frequencies. These data suggested that both local and large-scale phase synchrony in the alpha-, beta-, and gamma-frequency bands in the frontoparietal and visual regions could be a systems level mechanism for coordinating and regulating the maintenance of visual information in VWM. In addition, it suggested that beta-band oscillations may provide a mechanism for estimating short temporal durations, while gamma, alpha and theta-alpha oscillations support their encoding, retrieval, and maintenance in working memory, respectively.
  • Lesnikova, Angelina (Helsingin yliopisto, 2021)
    Induction of neuronal plasticity by drugs and physiological mechanisms has been an important topic in the modern neuroscience investigations due to its potential to restore functions in a wide range of disorders. However, significant progress in this area has been hampered by the lack of knowledge on the precise mechanisms and underlying molecular pathways. Perineuronal nets (PNNs), extracellular matrix structures that are particularly abundant around parvalbumin-containing (PV+) neurons, mature towards the end of the critical period in the brain development and inhibit neuronal plasticity. However, molecular pathways affected by PNN composition are not well known. On the other hand, tropomyosin receptor kinase B (TRKB), receptor for brain-derived neurotrophic factor (BDNF), is a well-recognized facilitator of plastic changes in the central nervous system. Whether these two opposing mechanisms converge on any common molecular pathway has not been identified previously. In the first study, we identified that perineuronal nets inhibit flexibility of neuronal cells and circuits through binding to receptor-like protein tyrosine phosphatase sigma (PTPσ), which subsequently dephosphorylates and inactivates TRKB. Specifically, we found that PNN component aggrecan restricts TRKB phosphorylation, while PNN removal by enzymatic activity of chondroitinase ABC (chABC) increases TRKB phosphorylation in neuronal cultures in vitro. We also found that a well-known ability of chABC to induce ocular dominance plasticity in the adult brain is dependent on TRKB, as mice deficient for TRKB in parvalbumin neurons (PV-TRKB+/-) do not exhibit enhanced plasticity in the visual cortex after chondroitinase treatment. We discovered that genetic knockdown of the PNN receptor PTPσ facilitates TRKB activation in vitro and in vivo, and that adult PTPσ+/- mice have juvenile-like plasticity in the visual cortex. We confirmed that TRKB and PTPσ display interaction in vitro, and identified that interaction occurs in the transmembrane domain. Finally, we found that the interaction between TRKB and PTPσ is diminished by antidepressant fluoxetine in vitro and in vivo. Altogether, our study suggests that chABC and antidepressant treatment induce plasticity through activation of TRKB by relaxing dephosphorylating control of PTPσ over it. In the second study, we focused on studying the molecular and behavioral phenotype of increased tonic plasticity displayed by genetic deficiency of PTPσ. We found that PTPσ+/- mice have increased phosphorylation of PLCγ1 but not Akt or Erk, suggesting that PTPσ specifically modulates PLCγ1 but not the other TRKB downstream signaling pathways. We did not find any changes in the expression levels of PSD-93, PSD-95 or in the number of excitatory synapses in their brain, suggesting that their phenotype cannot be explained by an altered number of synapses. We carried out a battery of behavior tests and discovered that PTPσ+/- mice have improved short-term and deteriorated long-term memory, as evident from their performance in the novel object recognition and fear conditioning tests. Finally, these mice do not exhibit any behavior abnormalities in elevated plus maze, open field, marble burying or forced swim test, suggesting that their behavioral changes are specific for tests requiring cognitive flexibility. We propose the term "hyperplasticity" to describe the PTPσ+/- mouse phenotype. Altogether, the current PhD project investigated the interaction between perineuronal nets, transmembrane phosphatase PTPσ and tyrosine receptor kinase TRKB in mediating plasticity in the brain.