Models for the Study of Cortical Activity During Cognitive ans Motor Tasks

This thesis is mainly devoted to show how EEG data and related phenomena can be reproduced and analyzed using mathematical models of neural masses (NMM). The aim is to describe some of these phenomena, to show in which ways the design of the models architecture is influenced by such phenomena, point out the difficulties of tuning the dozens of parameters of the models in order to reproduce the activity recorded with EEG systems during different kinds of experiments, and suggest some strategies to cope with these problems. In particular the chapters are organized as follows: chapter I gives a brief overview of the aims and issues addressed in the thesis; in chapter II the main characteristics of the cortical column, of the EEG signal and of the neural mass models will be presented, in order to show the relationships that hold between these entities; chapter III describes a study in which a NMM from the literature has been used to assess brain connectivity changes in tetraplegic patients; in chapter IV a modified version of the NMM is presented, which has been developed to overcomes some of the previous version’s intrinsic limitations; chapter V describes a study in which the new NMM has been used to reproduce the electrical activity evoked in the cortex by the transcranial magnetic stimulation (TMS); chapter VI presents some preliminary results obtained in the simulation of the neural rhythms associated with memory recall; finally, some general conclusions are drawn in chapter VII.

Cognitive and behavioural assessment of parkinsonian syndromes at onset: a longitudinal study

Background: cognitive impairment is one of the non motor features widely descripted in parkinsonian syndrome, it has been related to the motor characteristics of the parkinsonian syndrome, associated with neuropsychiatric dysfunction and the characteristic sleep and autonomic features. It has been shown to be highly prevalent at all disease stages and to contribute significantly to disability. Objectives: aim of this study is to evaluate longitudinally the cognitive and behavioral characteristics of patients with a parkinsonian syndrome at onset; to describe the cognitive and behavioral characteristics of each parkinsonian syndrome; to define in PD patients at onset the presence of MCI or Parkinson disease dementia; to correlate the cognitive and behavioral characteristics with the features of the parkinsonian syndrome and with the associated sleep and autonomic features. Results: we recruited 55 patients, 22 did not present cognitive impairment both at T0 and at T1. 18 patients presented a progression of cognitive impairment. Progressive cognitively impaired patients were older and presented the worst motor phenotype. Progression of cognitive impairment was not associated to sleep and autonomic features. Conclusion: the evaluation of cognitive impairment could not be useful as a predictor of a correct diagnosis but each non motor domain will help to clarify and characterize the motor syndrome. The diagnosis of parkinsonian disorders lies in building a clinical profile in conjunction with other clinical characteristics such as mode of presentation, disease progression, response to medications, sleep and autonomic features.

Methods for objective and interpretative evaluation of function and motor control: gait in perturbed condition and in the aquatic therapy

Gait analysis allows to characterize motor function, highlighting deviations from normal motor behavior related to an underlying pathology. The widespread use of wearable inertial sensors has opened the way to the evaluation of ecological gait, and a variety of methodological approaches and algorithms have been proposed for the characterization of gait from inertial measures (e.g. for temporal parameters, motor stability and variability, specific pathological alterations). However, no comparative analysis of their performance (i.e. accuracy, repeatability) was available yet, in particular, analysing how this performance is affected by extrinsic (i.e. sensor location, computational approach, analysed variable, testing environmental constraints) and intrinsic (i.e. functional alterations resulting from pathology) factors. The aim of the present project was to comparatively analyze the influence of intrinsic and extrinsic factors on the performance of the numerous algorithms proposed in the literature for the quantification of specific characteristics (i.e. timing, variability/stability) and alterations (i.e. freezing) of gait. Considering extrinsic factors, the influence of sensor location, analyzed variable, and computational approach on the performance of a selection of gait segmentation algorithms from a literature review was analysed in different environmental conditions (e.g. solid ground, sand, in water). Moreover, the influence of altered environmental conditions (i.e. in water) was analyzed as referred to the minimum number of stride necessary to obtain reliable estimates of gait variability and stability metrics, integrating what already available in the literature for over ground gait in healthy subjects. Considering intrinsic factors, the influence of specific pathological conditions (i.e. Parkinson’s Disease) was analyzed as affecting the performance of segmentation algorithms, with and without freezing. Finally, the analysis of the performance of algorithms for the detection of gait freezing showed how results depend on the domain of implementation and IMU position.

Mathematical skills: intergenerational features and relationships with cognitive and linguistic abilities

This thesis aimed to investigate the cognitive underpinnings of math skills, with particular reference to cognitive, and linguistic markers, core mechanisms of number processing and environmental variables. In particular, the issue of intergenerational transmission of math skills has been deepened, comparing parents’ and children’s basic and formal math abilities. This pattern of relationships amongst these has been considered in two different age ranges, preschool and primary school children. In the first chapter, a general introduction on mathematical skills is offered, with a description of some seminal works up to recent studies and latest findings. The first chapter concludes with a review of studies about the influence of environmental variables. In particular, a review of studies about home numeracy and intergenerational transmission is examined. The first study analyzed the relationship between mathematical skills of children attending primary school and those of their mothers. The objective of this study was to understand the influence of mothers' math abilities on those of their children. In the second study, the relationship between parents’ and children numerical processing has been examined in a sample of preschool children. The goal was to understand how mathematical skills of parents were relevant for the development of the numerical skills of children, taking into account children’s cognitive and linguistic skills as well as the role of home numeracy. The third study had the objective of investigating whether the verbal and nonverbal cognitive skills presumed to underlie arithmetic are also related to reading. Primary school children were administered measures of reading and arithmetic to understand the relationships between these two abilities and testing for possible shared cognitive markers. Finally, in the general discussion a summary of main findings across the study is presented, together with clinical and theoretical implications.

Seeing emotions in others: Improving cognitive and neuronal mechanisms of facial expression processing

In the conceptual framework of affective neuroscience, this thesis intends to advance the understanding of the plasticity mechanisms of other’s emotional facial expression representations. Chapter 1 outlines a description of the neurophysiological bases of Hebbian plasticity, reviews influential studies that adopted paired associative stimulation procedures, and introduces new lines of research where the impact of cortico-cortical paired associative stimulation protocols on higher order cognitive functions is investigated. The experiments in Chapter 2 aimed to test the modulatory influence of a perceptual-motor training, based on the execution of emotional expressions, on the subsequent emotion intensity judgements of others’ high (i.e., full visible) and low-intensity (i.e., masked) emotional expressions. As a result of the training-induced learning, participants showed a significant congruence effect, as indicated by relatively higher expression intensity ratings for the same emotion as the one that was previously trained. Interestingly, although judged as overall less emotionally intense, surgical facemasks did not prevent the emotion-specific effects of the training to occur, suggesting that covering the lower part of other’s face do not interact with the training-induced congruence effect. In Chapter 3 it was implemented a transcranial magnetic stimulation study targeting neural pathways involving re-entrant input from higher order brain regions into lower levels of the visual processing hierarchy. We focused on cortical visual networks within the temporo-occipital stream underpinning the processing of emotional faces and susceptible to plastic adaptations. Importantly, we tested the plasticity-induced effects in a state dependent manner, by administering ccPAS while presenting different facial expressions yet afferent to a specific emotion. Results indicated that the discrimination accuracy of emotion-specific expressions is enhanced following the ccPAS treatment, suggesting that a multi-coil TMS intervention might represent a suitable tool to drive brain remodeling at a neural network level, and consequently influence a specific behavior.

Models for the study of neuronal activity during cognitive tasks

Assessment of brain connectivity among different brain areas during cognitive or motor tasks is a crucial problem in neuroscience today. Aim of this research study is to use neural mass models to assess the effect of various connectivity patterns in cortical EEG power spectral density (PSD), and investigate the possibility to derive connectivity circuits from EEG data. To this end, two different models have been built. In the first model an individual region of interest (ROI) has been built as the parallel arrangement of three populations, each one exhibiting a unimodal spectrum, at low, medium or high frequency. Connectivity among ROIs includes three parameters, which specify the strength of connection in the different frequency bands. Subsequent studies demonstrated that a single population can exhibit many different simultaneous rhythms, provided that some of these come from external sources (for instance, from remote regions). For this reason in the second model an individual ROI is simulated only with a single population. Both models have been validated by comparing the simulated power spectral density with that computed in some cortical regions during cognitive and motor tasks. Another research study is focused on multisensory integration of tactile and visual stimuli in the representation of the near space around the body (peripersonal space). This work describes an original neural network to simulate representation of the peripersonal space around the hands, in basal conditions and after training with a tool used to reach the far space. The model is composed of three areas for each hand, two unimodal areas (visual and tactile) connected to a third bimodal area (visual-tactile), which is activated only when a stimulus falls within the peripersonal space. Results show that the peripersonal space, which includes just a small visual space around the hand in normal conditions, becomes elongated in the direction of the tool after training, thanks to a reinforcement of synapses.

Archaeological Baltic amber: degradation mechanisms and conservation measures

The aim of this project was to achieve a deep understanding of the mechanisms by which Baltic amber degrades, in order to develop techniques for preventive conservation of archaeological amber objects belonging to the National Museum of Denmark’s collections. To examine deterioration of Baltic amber, a starting point was to identify and monitor surface and bulk properties which are affected during degradation. The way to operate consisted of the use of accelerated ageing to initiate degradation of raw Baltic amber samples in different conditions of relative humidity, oxygen exposure or pH and, successively, of the use of non/micro-destructive techniques to identify and quantify changes in visual, chemical and structural properties. A large piece of raw Baltic amber was used to prepare several test samples for two different kinds of accelerated ageing: thermal-ageing and photo-ageing. During the ageing, amber samples were regularly examined through several analytical techniques related to different information: appearance/colour change by visual examination, photography and colorimetry; chemical change by infrared spectroscopy, Raman spectroscopy and elemental analysis; rate of oxidation by oxygen measurement; qualitative analysis of released volatiles by gas chromatography – mass spectrometry. The obtained results were analysed through both critical evaluation and statistical study. After the interpretation of the achieved data, the main relations between amber and environmental factors during the degradation process became clearer and it was possible to identify the major pathways by which amber degrades, such as hydrolysis of esters into alcohols and carboxylic acids, thermal-oxidation and photo-oxidation of terpenoid components, depolymerisation and decomposition of the chemical structure. At the end it was possible to suggest a preventive conservation strategy based on the control of climatic, atmospheric and lighting parameters in the environment where Baltic amber objects are stored and displayed.

Cognitive and affective processes in social actions and decisions

The question of how we make, and how we should make judgments and decisions has occupied thinkers for many centuries. This thesis has the aim to add new evidences to clarify the brain’s mechanisms for decisions. The cognitive and the emotional processes of social actions and decisions are investigated with the aim to understand which brain areas are mostly involved. Four experimental studies are presented. A specific kind of population is involved in the first study (as well as in study III) concerning patients with lesion of ventromedial prefrontal cortex (vmPFC). This region is collocated in the ventral surface of frontal lobe, and it seems have an important role in social and moral decision in forecasting the negative emotional consequences of choice. In study I, it is examined whether emotions, specifically social emotions subserved by the vmPFC, affect people’s willingness to trust others. In study II is observed how incidental emotions could encourage trusting behaviour, especially when individuals are not aware of emotive stimulation. Study III has the aim to gather a direct psychophysiological evidence, both in healthy and neurologically impaired individuals, that emotions are crucially involved in shaping moral judgment, by preventing moral violations. Study IV explores how the moral meaning of a decision and its subsequent action can modulate the basic component of action such as sense of agency.

Stochastic models and dynamic measures for the characterization of bistable circuits

During the last few years, a great deal of interest has risen concerning the applications of stochastic methods to several biochemical and biological phenomena. Phenomena like gene expression, cellular memory, bet-hedging strategy in bacterial growth and many others, cannot be described by continuous stochastic models due to their intrinsic discreteness and randomness. In this thesis I have used the Chemical Master Equation (CME) technique to modelize some feedback cycles and analyzing their properties, including experimental data. In the first part of this work, the effect of stochastic stability is discussed on a toy model of the genetic switch that triggers the cellular division, which malfunctioning is known to be one of the hallmarks of cancer. The second system I have worked on is the so-called futile cycle, a closed cycle of two enzymatic reactions that adds and removes a chemical compound, called phosphate group, to a specific substrate. I have thus investigated how adding noise to the enzyme (that is usually in the order of few hundred molecules) modifies the probability of observing a specific number of phosphorylated substrate molecules, and confirmed theoretical predictions with numerical simulations. In the third part the results of the study of a chain of multiple phosphorylation-dephosphorylation cycles will be presented. We will discuss an approximation method for the exact solution in the bidimensional case and the relationship that this method has with the thermodynamic properties of the system, which is an open system far from equilibrium.In the last section the agreement between the theoretical prediction of the total protein quantity in a mouse cells population and the observed quantity will be shown, measured via fluorescence microscopy.

Integration of cognitive and affective processes in perception and decision-making

The relationship between emotion and cognition is a topic that raises great interest in research. Recently, a view of these two processes as interactive and mutually influencing each other has become predominant. This dissertation investigates the reciprocal influences of emotion and cognition, both at behavioral and neural level, in two specific fields, such as attention and decision-making. Experimental evidence on how emotional responses may affect perceptual and attentional processes has been reported. In addition, the impact of three factors, such as personality traits, motivational needs and social context, in modulating the influence that emotion exerts on perception and attention has been investigated. Moreover, the influence of cognition on emotional responses in decision-making has been demonstrated. The current experimental evidence showed that cognitive brain regions such as the dorsolateral prefrontal cortex are causally implicated in regulation of emotional responses and that this has an effect at both pre and post decisional stages. There are two main conclusions of this dissertation: firstly, emotion exerts a strong influence on perceptual and attentional processes but, at the same time, this influence may also be modulated by other factors internal and external to the individuals. Secondly, cognitive processes may modulate emotional prepotent responses, by serving a regulative function critical to driving and shaping human behavior in line with current goals.

Assessing the state of Nephrops norvegicus and management measures in the Central Adriatic Sea

Nephrops norvegicus is a sedentary bottom-dwelling crustacean that represents one of the main commercial species exploited in the Adriatic Sea (Central Mediterranean). An evaluation of the status of this important resource is thus extremely important in order to manage it in a sustainable way. The evaluation of N. norvegicus is complicated by several issues, mainly: (i) the complex biology and behaviour of the species itself, (ii) the presence of subpopulations with different biological traits within the same stock unit. Relevant concentration of N.norvegicus occurs within the Pomo/Jabuka Pits area which is characterised by peculiar oceanographic and geophysical conditions. This area represented for a long time an important fishing ground shared by Italian and Croatian fleets and recently a Fishery Restricted Area (FRA) was established there. The aim of the present study is to perform for the first time an evaluation of the status of the N.norvegicus subpopulation inhabiting the Pomo/Jabuka Pits also accounting for the possible effects on it of the management measures. To achieve this, the principal fisheryindependent and fishery-dependent dataset available for the study area were firstly analysed and then treated. Data collected by the CNR-IRBIM of Ancona through both indirect (“UWTV”) and direct (trawling) methods were refined by means of a revision of the time series and related biases, and a modelling approach accounting for environmental and fishery effects, respectively. Commercial data for both Italy and Croatia were treated in order to obtain landings and length distributions for the Pomo area only; an historical reconstruction of data starting from 1970 was carried out for both countries. The obtained information was used as input for a Bayesian length-based stock assessment model developed through the CASAL software; the flexibility of this model is recommended for N.norvegicus and similar species allowing to deal with sex- and fleet-based integrated assessment method

The Financial Services Regime in International Economic Law: on the Difficult Relationship between Trade Liberalization and Prudential Measures

The PhD thesis analyses the financial services regime in international economic law from the perspective of the difficult relationship between trade liberalisation and prudential measures. Financial stability plays a fundamental role for the well-being and well-functioning of the global economy, but, it is at the same time a complex sector to regulate and supervise and, especially after the 2007-08 economic crisis, States have tightened up their regulation of financial services, introducing more severe and protectionist prudential measures. However, in an increasingly interconnected global economy, the harmonization of prudential regulation at the international level is an essential step to guarantee integrity, fairness and stability of financial markets and trade. The research analyses the tools at disposition to achieve this aim, the related problematic issues and the perspectives and possible solutions for the future, starting from the World Trade Organization (WTO) legal framework and its General Agreement on Trade in Services (GATS), devoted to discipline trade in services among the WTO Members. Then, the research moves to a second legal instrument, the Free Trade Agreements (FTAs), which has witnessed a remarkable spread in the last decades. Finally, the research addresses the international standards, developed by supranational entities and implemented by an increasing number of States, as they offer rules and guidelines adequate to update the international financial scenario. Nevertheless, the international standards alone cannot be the solution because, first, they are not mandatory, as governments decide voluntarily to apply them and, second, their decision-making process do not respect the requirements of transparency and representative membership. In light of this analysis, the thesis aims at providing an answer to its research question: how to give more certainty to States and economic operators in the planning of the domestic disciplines and business activities in order to provide a sound and stable international financial system.

The psychoactive effects of “Light Cannabis”. From Italian law to psychopharmacology

In 2019, the Italian Supreme Court established that hemp, for non-medical use, cannot be commercialized for human use, when the “psychotropic effect” of the product or its “offensiveness” can be demonstrated. The first chapter of this work reports a review of the European and Italian legislation on hemp cultivation, as well as the hemp production chain and commercial activities. The second chapter reports the pharmacological aspects and the psychoactive effects of light cannabis, along with pharmacokinetics of the main Cannabis compounds: Δ9-tetrahydrocannabinol (Δ9-THC), Cannabidiol (CBD) and Cannabinol (CBN). The aim of the experimental study, reported in the third chapter, is to assess Δ9-THC and CBD blood concentrations after smoking “light cannabis”, and its effects on vigilance, cognitive and motor skills. Eighteen young adults consumed three light cannabis cigarettes with a percentage of 0.41% of Δ9-THC and of 12.41% of CBD. Blood samples were collected before the experiment (t0) and after pre-defined time-lapses. Five performance tasks and a subjective scale were employed for measuring cognitive and psychomotor performances the day before the experiment (TT0) and after the third cigarette (TT1). Mean (SD) concentrations (ng/ml) were between 1.0(0.8) in t1 and 0.3(0.3) in t5 for Δ9-THC; and 10.5(10.3) in t1 and 5.7(5.7) in t5 for CBD. No significant differences were observed between TT0 and TT1 for all performed psychomotor performance task. Δ9-THC and CBD concentrations showed a high inter-subject variability, and the average concentrations were lower than those previously reported. Toxicological results showed a decrease of Δ9-THC and CBD after the third light cannabis cigarette, and a Δ9-THC /CBD ratio always < 1 was observed. This value might be useful in discriminating light cannabis versus illegal/medical cannabis consumption. The lack of impairment observed in our participants can be interpreted as a consequence of the very low concentrations in the blood.

Sonno e funzioni cognitive: ruolo della microstruttura del sonno NREM

STUDY OBJECTIVE: Cyclic Alternating Pattern (CAP) is a fluctuation of the arousal level during NREM sleep and consists of the alternation between two phases: phase A (divided into three subtypes A1, A2, and A3) and phase B. A1 is thought to be generated by the frontal cortex and is characterized by the presence of K complexes or delta bursts; additionally, CAP A1 seems to have a role in the involvement of sleep slow wave activity in cognitive processing. Our hypothesis was that an overall CAP rate would have a negative influence on cognitive performance due to excessive fluctuation of the arousal level during NREM sleep. However, we also predicted that CAP A1 would be positively correlated with cognitive functions, especially those related to frontal lobe functioning. For this reason, the objective of our study was to correlate objective sleep parameters with cognitive behavioral measures in normal healthy adults. METHODS: 8 subjects (4 males; 4 females; mean age 27.75 years, range 2334) were recruited for this study. Two nocturnal polysomnography (night 2 and 3 = N2 and N3) were carried out after a night of adaptation. A series of neuropsychological tests were performed by the subjects in the morning and afternoon of the second day (D2am; D2pm) and in the morning of the third day (D3am). Raw scores from the neuropsychological tests were used as dependent variables in the statistical analysis of the results. RESULTS: We computed a series of partial correlations between sleep microstructure parameters (CAP, A1, A2 and A3 rate) and a number of indices of cognitive functioning. CAP rate was positively correlated with visuospatial working memory (Corsi block test), Trial Making Test Part A (planning and motor sequencing) and the retention of words from the Hopkins Verbal Learning Test (HVLT). Conversely, CAP was negatively correlated with visuospatial fluency (Ruff Figure Fluency Test). CAP A1 were correlated with many of the tests of neuropsychological functioning, such as verbal fluency (as measured by the COWAT), working memory (as measured by the Digit Span – Backward test), and both delay recall and retention of the words from the HVLT. The same parameters were found to be negatively correlated with CAP A2 subtypes. CAP 3 were negatively correlated with the Trial Making Test Parts A and B. DISCUSSION: To our knowledge this is the first study indicating a role of CAP A1 and A2 on behavioral cognitive performance of healthy adults. The results suggest that high rate of CAP A1 might be related to an improvement whereas high rate of CAP A2 to a decline of cognitive functions. Further studies need to be done to better determine the role of the overall CAP rate and CAP A3 on cognitive behavioral performances.

Uncovering the encoding and transmission of behaviourally relevant information in neural activity

Most cognitive functions require the encoding and routing of information across distributed networks of brain regions. Information propagation is typically attributed to physical connections existing between brain regions, and contributes to the formation of spatially correlated activity patterns, known as functional connectivity. While structural connectivity provides the anatomical foundation for neural interactions, the exact manner in which it shapes functional connectivity is complex and not yet fully understood. Additionally, traditional measures of directed functional connectivity only capture the overall correlation between neural activity, and provide no insight on the content of transmitted information, limiting their ability in understanding neural computations underlying the distributed processing of behaviorally-relevant variables. In this work, we first study the relationship between structural and functional connectivity in simulated recurrent spiking neural networks with spike timing dependent plasticity. We use established measures of time-lagged correlation and overall information propagation to infer the temporal evolution of synaptic weights, showing that measures of dynamic functional connectivity can be used to reliably reconstruct the evolution of structural properties of the network. Then, we extend current methods of directed causal communication between brain areas, by deriving an information-theoretic measure of Feature-specific Information Transfer (FIT) quantifying the amount, content and direction of information flow. We test FIT on simulated data, showing its key properties and advantages over traditional measures of overall propagated information. We show applications of FIT to several neural datasets obtained with different recording methods (magneto and electro-encephalography, spiking activity, local field potentials) during various cognitive functions, ranging from sensory perception to decision making and motor learning. Overall, these analyses demonstrate the ability of FIT to advance the investigation of communication between brain regions, uncovering the previously unaddressed content of directed information flow.