The ability to experience, use, and eventually control anger is crucial for maintaining well-being, achieving our goals, and building healthy relationships. Despite its relevance, the neural and psychological mechanisms behind this emotion are still in their early stages. Therefore, the present work represents an effort towards the investigation of these features of anger, where the ambition is to take a step forward to bridge the gaps between the research and clinical fields. Chapter 1 will expose an introduction on anger, while Chapter 2 will expose the evidence in literature on the neural bases of anger relying on a meta-analytic approach, where the neural bases of anger perception and anger experience will be investigated. Chapter 3 relies on a multivariate data-driven approach in order to study the neural networks of anger-related individual differences, identifying a structural network associated with trait anger and a functional network associated with anger control. Chapter 4 focuses on the neural bases of other anger-related individual differences, relying on functional connectivity analysis to investigate the frontal asymmetry hypothesis, finding an association of a left pattern of connectivity with anger externalization and a right pattern of connectivity with anger internalization. Finally, the following two chapters focused on the regulation of anger, in particular considering two different strategies, reappraisal versus suppression, and the related effect of a mindfulness course on the regulation of anger. The final chapter will summarize the evidence provided in this thesis in order to integrate the different results.

During speech perception listeners receive both linguistic information about the speech content as well as information regarding the identity of the talker. While these two aspects have been traditionally studied in isolation, with a dominant interest for linguistic information over talker identity, it is now a widely accepted notion that these two kinds of information are processed in an integrated way. The inclusion of talker-related information in the domain of speech perception highlighted both benefits and challenges for listeners. On the one hand, linguistic and talker-identity information appear to be mutually beneficial for the extraction of both kinds of information from the speech signal. On the other hand, listeners must take care of the great acoustic variability that characterizes the physical dimensions linked to the two kinds of information. The aim of the present dissertation is to study three specific cognitive mechanisms that listeners can use to access the benefits of the integrated processing of linguistic and talker-related information as well as to deal with their intrinsic variability. Three empirical studies employing both behavioural and neurophysiological techniques highlight peculiar aspects of abstraction, memory retrieval and perceptual learning mechanisms in relation to the consequences of including the talker in the study of speech perception.

The presence of networks of correlation between gray matter volumes of brain regions - as measured across subjects in a group of individuals - has been consistently described in several human studies, an approach termed structural covariance MRI (scMRI). Complementary to prevalent brain connectivity modalities like functional and diffusion-weighted imaging, this approach can provide valuable insight into the mutual influence of regional trophic and plastic processes occurring between brain regions. Previous investigations highlighted coordinated growth of these regions within specific structural networks in healthy populations and described their derangement in pathological states. However, a number of fundamental questions about the origin and significance of these couplings remains open and the mechanisms behind the formation of scMRI networks are still poorly understood. To investigate whether analogous scMRI networks are present in lower mammal species amenable to genetic and experimental manipulation such as the laboratory mouse, I coupled high resolution morpho-anatomical MRI with network-based approaches on a large cohort of genetically-homogeneous wild-type mice (C57Bl6/J). To this purpose, I first developed a semi-automated pipeline enabling reliable Voxel Based Morphometry (VBM) of gray matter volumes in the mouse. To validate this approach and its ability to detect plastic changes in brain structures, I applied it to a cohort of aged mice treated with omega-3 polyunsaturated fatty acids (n3-PUFA). This study revealed that treatment with n3PUFA, but not isocaloric olive oil preserved gray matter volume of the hippocampus and frontal cortices, an effect coincident with amelioration of hippocampal-based spatial memory functions. I next employed VBM to investigate scMRI networks in inbred mice using a seed-based approach. In striking resemblance with human findings, I observed the presence of homotopic (i.e. bilateral) architecture in several scMRI cortical and subcortical networks, a finding corroborated by Independent Component Analyses. Subcortical structures also showed highly symmetric inter-hemispheric correlations, with evidence of distributed antero-posterior networks in diencephalic regions of the thalamus and hypothalamus. Hierarchical cluster analysis revealed six identifiable clusters of cortical and sub-cortical regions corresponding to previously described neuroanatomical systems. This work documents for the first time the presence of homotopic cortical and subcortical scMRI networks in the mouse brain, and is poised to pave the way to translational use of this species to investigate the elusive biological and neuroanatomical underpinnings of scMRI network development and its derangement in neuropathological states.

When we observe other people's actions, a network of temporal, parietal and frontal regions is recruited, known as action observation network (AON). This network includes areas that have been reported to be involved when we perform actions ourselves. Such findings support the view that action understanding occurs by simulating actions in our own motor system (motor theories of action understanding). Alternatively, it has been argued that actions are understood based on a perceptual analysis, with access to action knowledge stored in the conceptual system (cognitive theories of action understanding). It has been argued earlier that areas that play a crucial role for action understanding should be able to (a) distinguish between different actions, and (b) generalize across the ways in which the action is performed (e.g. Dinstein, Thomas, Behrmann, & Heeger, 2008; Oosterhof, Tipper, & Downing, 2013; Caramazza, Anzelotti, Strnad, & Lingnau, 2014). Here we argue that one additional criterion needs to be met: an area that plays a crucial role for action understanding should have access to such abstract action information early, around the time when the action is recognized. An area that has access to abstract action information after the action has been recognized is unlikely to contribute to the process of action understanding. In this thesis, I report three neuroimaging studies in which we used magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) to characterize the temporal dynamics of abstract representations of observed actions (Study 1 and 2), meaning that generalize across lower level dimensions, and to characterize the type of information encoded in the regions of the AON (Study 3). Specifically, in Study 1 we examined where in the brain and at which point in time it is possible to distinguish between pointing and grasping actions irrespective of the way in which they are performed (reach direction, effector) using MEG in combination with multivariate pattern analysis (MVPA) and source analysis. We show that regions in the left lateral occipitotemporal cortex (LOTC) have the earliest access to abstract action representations. By contrast, precentral regions, though recruited relatively early, have access to abstract action representations substantially later than left LOTC. In Study 2, we tested the temporal dynamics of the neural decoding related to the oscillatory activity induced by observation of actions performed with different effectors (hand, foot). We observed that temporal regions are able to discriminate all the presented actions before effector-related decoding within effector-specific motor regions. Finally, in Study 3 we investigated what aspect of an action is encoded within the regions of the AON. Object-directed actions induce a change of states, e.g. opening a bottle means changing its state from closed to open. It is still unclear how and in which brain regions these neural representations are encoded. Using fMRI-based multivoxel pattern decoding, we aimed at dissociating the neural representations of states and action functions. Participants observed stills of objects (e.g., window blinds) that were in either open or closed states, and videos of actions involving the same objects, i.e., open or close window. Action videos could show the object manipulation only (invisible change), or the complete action scene (visible change). This design allowed us to detect neural representations of action scenes, states and action functions independently of each other. We found different sub-regions within LOTC containing information related to object states, action functions, or both. These findings provide important information regarding the organization of action semantics in the brain and the role of LOTC in action understanding.

Finding one’s way back to a safe refuge or recalling the best place to find food is essential to all animals including human beings. We engage in future actions based on past events. So how does our brain compute such important cognitive tasks? Is it an innate ability we have from birth that is hardwired into the blueprint of our brains? And what happens if for some reason we realize that we are unable to perform these cognitive abilities in old age or due to a neurological disorder? The hippocampus is the main area of the brain involved in memory and learning. Animal studies show evidence of its role in spatial navigation and memory. The complex network of spatial cells in the hippocampus, all participate in constructing a cognitive map in the brain, where an animal stores information about the external environment and uses it to engage in future actions. However, despite the importance in its function, the hippocampus is also one of the first areas of the brain to be affected by aging and other neurological disorders. The present thesis used the help of various animal models to answer three questions: first whether hippocampal function is present immediately at birth, second whether genes can regulate hippocampal activity and third whether a sensitive task such as reorientation can highlight hippocampal alteration caused by age. To answer the first question, we used the domestic chick that has the advantage of being tested after hatching. We show evidence that a change in environmental shape can alter hippocampal activity in naïve chicks, suggesting that hippocampal function is present already in early stages of life. Furthermore, we investigated if genes regulate hippocampal activity. We used a mouse model that carried one half of the Williams syndrome deletion, a disorder known for its hippocampal deficit. We show evidence that genes on the proximal deletion of Williams syndrome deletion, can alter reorientation and episodic memory, two hippocampal related functions. Finally, we aimed to find an appropriate task to highlight the allocentric difficulty that arises in age. We used aged animals of two species (mice and rats) and tested them in the reorientation paradigm. We show that this simple task has potential to be a better suited assay to evaluate hippocampal behavior.

Lateralization of the nervous system enhances optimization of neural circuitry and parallel processing in individual organisms. Over groups of individuals, brain-behavioural asymmetries might present a direction in the occurrence of the bias (the majority of the individuals showing the same direction at the population level) that has been mathematically demonstrated to be an evolutionarily stable strategy in social groups, thus optimizing coordination and cooperation. The superfamily Apoidea represents a group in which both the study of the appearance of population-level asymmetries and advantages in individual organisms (e.g., in the A. mellifera model) can be exploited. Here I described a study on olfactory lateralization in a primitively eusocial species of Apoidea, B. terrestris. I reported here that this species showed a direction in the behavioural asymmetry of short-term odour memory, but only individual-level differences in odour detection at the periphery of the nervous system. Moreover, B. terrestris showed a morphological difference at the level of the population in the number of structures where olfactory neurons are housed. In the same subfamily Apoidea, the perennial eusocial honeybee, A. mellifera, is a good candidate for assessing neural correlates of odour asymmetries. Lateralization in olfactory memory was reported in this species in the past; here I performed for the first time a study of anatomical and functional asymmetries within the brain, in the first olfactory neuropils, the antennal lobes. I measured a subset of glomeruli in naïve individuals and found symmetrical volumes between the sides for those glomeruli that are mainly activated by odours that show lateralization in behvaiour. Furthermore, I performed single-antenna recall tests, conditioning bees to extend their proboscis (in the so-called PER paradigm) in association with those odours that more strongly activated functional responses in the selected glomerular subset. The behavioural tests showed an odour dependency in the capacity of bees to recall compounds with the two antennae. A broader subset of glomeruli was measured after long-term memory formation and symmetrical volumes were confirmed in all glomerular classes revealing also memory-dependent shrinkage effect. At the functional level, I performed in vivo calcium imaging data of the bee antennal lobes. Odor-evoked activity maps were recorded with two-photon microscopy allowing for better spatial and temporal resolution compared to conventional fluorescence microscopy. A first comparison between sides from wide-field fluorescence microscopy data showed a left/right difference in distance between odour representations and different mixture interactions within each lobe. In the same social species, A.mellifera, I reported the results of experiments measuring social interactions between pairs of bees with only one antenna in use, revealing that animals tested with only their right antenna in use exhibited better social context-dependent behaviours. Overall, these results provide new evidence for the occurrence of behavioural lateralizations at the population level, and identify some of their possible anatomical and functional correlates. Finally, in relation to previous studies these results tighten the link between the occurrence of population-level asymmetries and their evolution in a social context.

The ability of moving freely in the environment gives us the great advantage to directly interact with it, improving our discriminative abilities. For example, if we were to inspect an object without the chance to actively moving around it, then we could only rely on the information that we can extract from a single point of view with respect of the object. We would have restricted access to the object properties and we would then establish our decisions within those limits. Moving actively allow us to overcome these limitations and gain access to a more complete set of informations regarding the object. This would help us decide what to do next, whether or not to interact with an external object and, in case, providing hints on how to interact. To this extent moving and exploring the environment augment our discrimination abilities. Moreover, active movements help us to form a complete sense of space.

Successfully acting largely depends on moving at the right time. Consider a member of an orchestra just few instants before starting to play her piece. She should be ready not only to launch the planned movements when appropriate, but also to stop them if required. Action initiation and control are characteristic features of many of our daily life actions. There is a large amount of evidence in monkeys and humans suggesting that the dorsal premotor cortex (PMD) and the supplementary motor areas (SMA) might be critically involved in these features. However, the distinctive role of these areas is still matter of controversy. The aim of the present thesis is to provide some preliminary steps toward a comprehension of whether and how the human dorsal precentral areas may selectively contribute to action initiation and control. In doing this we shall introduce and discuss a series of transcranial magnetic stimulation (TMS) experiments carried out with two different paradigms, namely dual-coil TMS and single pulse TMS paradigm. These experiments were primarily devoted to explore the structural and functional properties of PMD. They also allowed us to assess whether PMD and SMA may be differentially and selectively involved in action control. In more detail, we first investigated the structural connectivity between PMD and the ipsilateral orofacial M1, introducing a novel dual-coil TMS approach. Results displayed the existence of short-latency influences of the left PMD on the ipsilateral orofacial M1, measured by recording motor evoked potentials (MEPs) in the orofacial muscles. Then, taking advantage of this novel approach, we started to explore the functional PMD-M1 connectivity. We tested the short-latency effects of TMS, as measured by changes in orofacial MEPs, during a delayed motor task. The results showed an inhibitory activity in the PMD-M1 module during the SET-period. We also manipulated the duration of the SET-period, to establish whether the effects were time-locked to the start of the delay period or rather time-locked to the predicted GO-signal. Hence, the investigation of the PMD-M1 connectivity paved us the way to explore, first, the role of PMD in initiating action and, then, the differential role of PMD and SMA in controlling and inhibiting action. Indeed, we run a further study, in which we carried out two single pulse TMS experiments. We first stimulated PMD during a stop-signal task, then we contrasted the PMD stimulation with SMA stimulation when participants underwent the same stop-signal task. There are five chapters to come. In Chapter 1 we shall review some key studies exploring anatomical and functional properties of PMD and SMA in both monkeys and humans, with particular emphasis on their putative role in action initiation and control. In Chapter 2 we shall focus on the methodological aspects of our experimental studies. In particular, we shall introduce the so-called twin- or dual-coil TMS paradigm, discuss its main approaches present in the literature and propose a variant of them. In Chapter 3 we shall present and discuss our first dual-coil TMS study exploring, for the first time, the ipsilateral PMD-corticofacial system connectivity. In Chapter 4 we shall examine three dual-coil TMS studies investigating the functional connectivity between PMD and ipsilateral M1 during a motor delayed task. Finally, in Chapter 5 we shall scrutinize two single pulse TMS studies capitalizing on a stop-signal task in order to assess the role of PMD and SMA in action control. Results and future lines of research will be sketched in the Concluding remarks.

One of the core human abilities is that of interpreting symbols. Prompted with a perceptual stimulus devoid of any intrinsic meaning, such as a written word, our brain can access a complex multidimensional representation, called semantic representation, which corresponds to its meaning. Notwithstanding decades of neuropsychological and neuroimaging work on the cognitive and neural substrate of semantic representations, many questions are left unanswered. The research in this dissertation attempts to unravel one of them: are the neural substrates of different components of concrete word meaning dissociated? In the first part, I review the different theoretical positions and empirical findings on the cognitive and neural correlates of semantic representations. I highlight how recent methodological advances, namely the introduction of multivariate methods for the analysis of distributed patterns of brain activity, broaden the set of hypotheses that can be empirically tested. In particular, they allow the exploration of the representational geometries of different brain areas, which is instrumental to the understanding of where and when the various dimensions of the semantic space are activated in the brain. Crucially, I propose an operational distinction between motor-perceptual dimensions (i.e., those attributes of the objects referred to by the words that are perceived through the senses) and conceptual ones (i.e., the information that is built via a complex integration of multiple perceptual features). In the second part, I present the results of the studies I conducted in order to investigate the automaticity of retrieval, topographical organization, and temporal dynamics of motor-perceptual and conceptual dimensions of word meaning. First, I show how the representational spaces retrieved with different behavioral and corpora-based methods (i.e., Semantic Distance Judgment, Semantic Feature Listing, WordNet) appear to be highly correlated and overall consistent within and across subjects. Second, I present the results of four priming experiments suggesting that perceptual dimensions of word meaning (such as implied real world size and sound) are recovered in an automatic but task-dependent way during reading. Third, thanks to a functional magnetic resonance imaging experiment, I show a representational shift along the ventral visual path: from perceptual features, preferentially encoded in primary visual areas, to conceptual ones, preferentially encoded in mid and anterior temporal areas. This result indicates that complementary dimensions of the semantic space are encoded in a distributed yet partially dissociated way across the cortex. Fourth, by means of a study conducted with magnetoencephalography, I present evidence of an early (around 200 ms after stimulus onset) simultaneous access to both motor-perceptual and conceptual dimensions of the semantic space thanks to different aspects of the signal: inter-trial phase coherence appears to be key for the encoding of perceptual while spectral power changes appear to support encoding of conceptual dimensions. These observations suggest that the neural substrates of different components of symbol meaning can be dissociated in terms of localization and of the feature of the signal encoding them, while sharing a similar temporal evolution.

From the methodological perspective, we validated the use of a recently introduced multivariate searchlight pattern classification method for the analysis of training effects in language studies. We found that, compared to the standard GLM method, the searchlight analysis has comparable and, in some cases, greater sensitivity in localizing BOLD signal changes, and thus it represents a promising complementary tool in studies of training. "