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Jovana Belic

Publications and source records attributed to Jovana Belic.

3 recordsLinked to original sources

Interplay between periodic stimulation and GABAergic inhibition in striatal network oscillations

The network oscillations are ubiquitous across many brain regions. In the basal ganglia, oscillations are also present at many levels and a wide range of characteristic frequencies have been reported to occur during both health and disease.The striatum is the input nucleus of the basal ganglia that receives massive glutamatergic inputs from the cortex and is highly susceptible to cortical oscillations. However, there is limited knowledge about the exact nature of this routing process and therefore, it is of key importance to understand how time-dependent, periodic external stimuli propagate through the striatal circuitry. Using a large-scale network model of the striatum and corticostriatal projections, here we try to elucidate the importance of specific GABAergic neurons and their interactions in shaping striatal oscillatory activity. Our results show that fast-spiking interneurons, despite their uncorrelated firing, might have a crucial role in the emergence of high-frequency oscillations in the medium spiny neuron population, even if their activity is kept low. Rather, what matters is the firing time relative to just a few other neurons within an oscillation cycle. Finally, we show how the state of ongoing activity, the strengths of different types of inhibitions, the density of outgoing projections, and the overall activity of striatal cells influence network activity. These results suggest that the propagation of oscillatory inputs into the medium spiny neuron population is efficient, if indirect, through fast-spiking interneurons. Therefore, pharmaceuticals that target fast-spiking interneurons may provide a novel treatment for regaining the spectral characteristics of striatal activity that correspond to the healthy state.\n\nAuthor SummaryThe striatum is the largest and primary gateway component of the BG, receiving glutamatergic inputs from all cortical areas and is highly susceptible to cortical oscillations. However, there is limited knowledge about the exact nature of this routing process and therefore, it is of key importance to understand how time-dependent, external stimuli propagate through the striatal circuitry. The vast majority of striatal neurons, at least 95% of them, are medium spiny neurons (MSNs) that are also the only source of output from the nucleus. Two of the most examined sources of GABAergic inhibition into MSNs are the feedback inhibition (FB) from the axon collaterals of the MSNs themselves, and the feedforward inhibition (FF) via the small population of fast-spiking interneurons (FSIs) comprising roughly 1-2% of striatal neurons. Using a large-scale network model of the striatum we systematically investigate the propagation of asynchronous periodic cortical inputs, throughout the physiologically relevant range, onto the striatal neurons and their influence on striatal network dynamics. Our results show that FSIs, despite their firing being uncorrelated, may play a crucial role in the efficient propagation of external oscillations onto MSNs. Finally, we show how the state of ongoing activity, the strengths of different types of inhibitions, the density of outgoing projections, and the overall activity of striatal cells influence network activity.

Neuroscience

Untangling cortico-striatal connectivity and cross-frequency coupling in L-DOPA-induced dyskinesia

We simultaneously recorded local field potentials in the primary motor cortex and sensorimotor striatum in awake, freely behaving, 6-OHDA lesioned hemi-parkinsonian rats in order to study the features directly related to pathological states such as parkinsonian state and levodopa-induced dyskinesia. We analysed the spectral characteristics of the obtained signals and observed that during dyskinesia the most prominent feature was a relative power increase in the high gamma frequency range at around 80 Hz, while for the parkinsonian state it was in the beta frequency range. Here we show that during both pathological states effective connectivity in terms of Granger causality is bidirectional with an accent on the striatal influence on the cortex. In the case of dyskinesia, we also found a high increase in effective connectivity at 80 Hz. In order to further understand the 80- Hz phenomenon, we performed cross-frequency analysis and observed characteristic patterns in the case of dyskinesia but not in the case of the parkinsonian state or the control state. We noted a large decrease in the modulation of the amplitude at 80 Hz by the phase of low frequency oscillations (up to ~10 Hz) across both structures in the case of dyskinesia. This may suggest a lack of coupling between the low frequency activity of the recorded network and the group of neurons active at ~80 Hz.

Neuroscience

Decoding of human hand actions to handle missing limbs in Neuroprosthetics

The only way we can interact with the world is through movements, and our primary interactions are via the hands, thus any loss of hand function has immediate impact on our quality of life. However, to date it has not been systematically assessed how coordination in the hands joints affects every day actions. This is important for two fundamental reasons. Firstly, to understand the representations and computations underlying motor control \"in-the-wild\" situations, and secondly to develop smarter controllers for prosthetic hands that have the same functionality as natural limbs. In this work we exploit the correlation structure of our hand and finger movements in daily-life. The novelty of our idea is that instead of averaging variability out, we take the view that the structure of variability may contain valuable information about the task being performed. We asked seven subjects to interact in 17 daily-life situations, and quantified behaviour in a principled manner using CyberGlove body sensor networks that, after accurate calibration, track all major joints of the hand. Our key findings are: 1. We confirmed that hand control in daily-life tasks is very low-dimensional, with four to five dimensions being sufficient to explain 80-90% of the variability in the natural movement data. 2. We established a universally applicable measure of manipulative complexity that allowed us to measure and compare limb movements across tasks. We used Bayesian latent variable models to model the low-dimensional structure of finger joint angles in natural actions. 3. This allowed us to build a naive classifier that within the first 1000ms of action initiation (from a flat hand start configuration) predicted which of the 17 actions was going to be executed - enabling us to reliably predict the action intention from very short-time-scale initial data, further revealing the foreseeable nature of hand movements for control of neuroprosthetics and tele operation purposes. 4. Using the Expectation-Maximization algorithm on our latent variable model permitted us to reconstruct with high accuracy (<5{degrees}-6{degrees} MAE) the movement trajectory of missing fingers by simply tracking the remaining fingers. Overall, our results suggest the hypothesis that specific hand actions are orchestrated by the brain in such a way that in the natural tasks of daily-life there is sufficient redundancy and predictability to be directly exploitable for neuroprosthetics.

Neuroscience