Matteo Mancini

I know that you know that I know: neural substrates associated with social cognition deficits in DM1 patients

Myotonic dystrophy type-1 (DM1) is a genetic multi-systemic disorder involving several organs including the brain. Despite the heterogeneity of this condition, some patients with non-congenital DM1 can present with minimal cognitive impairment on formal testing but with severe difficulties in daily-living activities including social interactions. One explanation for this paradoxical mismatch can be found in patients’ dysfunctional social cognition, which can be assessed in the framework of the Theory of Mind (ToM). We hypothesize here that specific disease driven abnormalities in DM1 brains may result in ToM impairments. We recruited 20 DM1 patients who underwent the “Reading the Mind in the Eyes” and the ToM-story tests. These patients, together with 18 healthy controls, also underwent resting-state functional MRI. A composite Theory of Mind score was computed for all recruited patients and correlated with their brain functional connectivity. This analysis provided the patients’ “Theory of Mind-network”, which was compared, for its topological properties, with that of healthy controls. We found that DM1 patients showed deficits in both tests assessing ToM. These deficits were associated with specific patterns of abnormal connectivity between the left inferior temporal and fronto-cerebellar nodes in DM1 brains. The results confirm the previous suggestions of ToM dysfunctions in patients with DM1 and support the hypothesis that difficulties in social interactions and personal relationships are a direct consequence of brain abnormalities, and not a reaction symptom. This is relevant not only for a better pathophysiological comprehension of DM1, but also for non-pharmacological interventions to improve clinical aspects and impact on patients’ success in life.

Assessing cortical synchronization during transcranial direct current stimulation: A graph-theoretical analysis.

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that can alter cortical excitability and modulate behaviour in a polarity-dependent way. Despite the widespread use of this method in the neuroscience field, its effects on ongoing local or global (network level) neuronal activity are still not foreseeable. A way to shed light on the neuronal mechanisms underlying the cortical connectivity changes induced by tDCS is provided by the combination of tDCS with electroencephalography (EEG). In this study, twelve healthy subjects underwent online tDCS-EEG recording (i.e., simultaneous), during resting-state, using 19 EEG channels. The protocol involved anodal, cathodal and sham stimulation conditions, with the active and the reference electrodes in the left frontocentral area (FC3) and on the forehead over the right eyebrow, respectively. The data were processed using a network model, based on graph theory and the synchronization likelihood. The resulting graphs were analysed for four frequency bands (theta, alpha, beta and gamma) to evaluate the presence of tDCS-induced differences in synchronization patterns and graph theory measures. The resting state network connectivity resulted altered during tDCS, in a polarity-specific manner for theta and alpha bands. Anodal tDCS weakened synchronization with respect to the baseline over the fronto-central areas in the left hemisphere, for theta band (p<0.05). In contrast, during cathodal tDCS a significant increase in inter-hemispheric synchronization connectivity was observed over the centro-parietal, centro-occipital and parieto-occipital areas for the alpha band (p<0.05). Local graph measures showed a tDCS-induced polarity-specific differences that regarded modifications of network activities rather than specific region properties. Our results show that applying tDCS during the resting state modulates local synchronization as well as network properties in slow frequency bands, in a polarity-specific manner.

Automatic artifact suppression in simultaneous tDCS-EEG using adaptive filtering.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method that can be used in cognitive and clinical protocols in order to modulate neural activity. Although some macro effects are known, the underlying mechanisms are still not clear. tDCS in combination with electroencephalography (EEG) could help to understand these mechanisms from a neural point of view. However, simultaneous tDCS-EEG still remains challenging because of the artifacts that affect the recorded signals. In this paper, an automated artifact cancellation method based on adaptive filtering is proposed. Using independent component analysis (ICA), the artifacts were characterized using data from both a phantom and a group of healthy subjects. The resulting filter can successfully remove tDCS-related artifacts during anodal and cathodal stimulations.

Currents induced by fast movements inside the MRI room may cause inhibition in an implanted pacemaker

The static magnetic field generated by MRI systems is highly non-homogenous and rapidly decreases when moving away from the bore of the scanner. Consequently, the movement around the MRI scanner is equivalent to an exposure to a time-varying magnetic field at very low frequency (few Hz). If people with an implanted pacemaker (PM) enter the MRI room, fast movements may thus induce voltages on the loop formed by the PM lead, with the potential to modify the correct behavior of the stimulator. In this study, we performed in-vitro measurements on a human-shaped phantom, equipped with an implantable PM and with a current sensor, able to monitor the activity of the PM while moving the phantom in the MRI room. Fast rotational movements in close proximity of the bore of the scanner caused the inappropriate inhibition of the PM, programmed in VVI modality, maximum sensitivity, unipolar sensing and pacing. The inhibition occurred for a variation of the magnetic field of about 3 T/s. These findings demonstrate that great care must be paid when extending PM MRI compatibility from patients to healthcare personnel, since the safety procedures and the MRI-conditional PM programming (e.g. asynchronous stimulation or bipolar sensing) used for patients cannot be applied.

A Pilot Study on Brain Plasticity of Functional Connectivity Modulated by Cognitive Training in Mild Alzheimer’s Disease and Mild Cognitive Impairment

Alzheimer’s disease (AD) alters the functional connectivity of the default mode network (DMN) but also the topological properties of the functional connectome. Cognitive training (CT) is a tool to slow down AD progression and is likely to impact on functional connectivity. In this pilot study, we aimed at investigating brain functional changes after a period of CT and active control (AC) in a group of 26 subjects with mild AD (mAD), 26 with amnestic mild cognitive impairment (aMCI), and a control group of 29 healthy elderly (HE) people. They all underwent a CT and AC in a counterbalanced order following a crossover design. Resting-state functional MRI and neuropsychological testing were acquired before and after each period. We tested post-CT and post-AC changes of cognitive abilities, of the functional connectivity of the DMN, and of topological network properties derived from graph theory and network-based statistics. Only CT produced functional changes, increasing the functional connectivity of the posterior DMN in all three groups. mAD also showed functional changes in the medial temporal lobe and topological changes in the anterior cingulum, whereas aMCI showed more widespread topological changes involving the frontal lobes, the cerebellum and the thalamus. Our results suggest specific functional connectivity changes after CT for aMCI and mAD.

Estimating multimodal brain connectivity in multiple sclerosis: An exploratory factor analysis

Graph-theoretical approaches have become a popular way to model brain data collected using magnetic resonance imaging (MRI), both from the structural and the functional perspectives. In structural networks, tract-based mapping allows to model different aspects of brain structures by means of the specific characteristics of the different MRI modalities. However, there has been little effort to join the information carried by each modality and to understand what level of common variance is shown in these data. In this paper, we proposed a combined approach based on graph theory and factor analysis to model magnetization transfer and microstructural properties in 18 relapsing remitting multiple sclerosis (RRMS) patients and 17 healthy controls. After defining the common factors and outlining their relationships with MRI data, we evaluated between-group differences using global and local graph measures. The results showed that one common factor describes brain structures in terms of myelin and global integrity, and such factor is able to highlight specific between-group differences.

Architectural Perspectives Survey

This paper deals with the problem of surveying Architectural Perspectives, generally painted in a 1:1 scale, which represent illusory spaces, enlarging the hosting real spaces. In particular, we intend to propose a method of survey, applicable to the case of painted surfaces in general; this method allows us to achieve high-resolution images with a large information content that gives us detailed information on the colours and on the painting construction signs, in addition to the metric data. For this purpose, we tested image-based integrated survey techniques, which aim, on the one hand, at the construction of three-dimensional virtual models through consolidated image-based modelling techniques, on the other at the construction of high resolution images that have metric valence.

Network abnormalities in generalized anxiety pervade beyond the amygdala-pre-frontal cortex circuit: Insights from graph theory

Generalized anxiety disorder (GAD) has excessive anxiety and uncontrollable worry as core symptoms. Abnormal cerebral functioning underpins the expression and perhaps pathogenesis of GAD:. Studies implicate impaired communication between the amygdala and the pre-frontal cortex (PFC). Our aim was to longitudinally investigate whether such network abnormalities are spatially restricted to this circuit or if the integrity of functional brain networks is globally disrupted in GAD. We acquired resting-state functional magnetic resonance imaging data from 16 GAD patients and 16 matched controls at baseline and after 1 year. Using network modeling and graph-theory, whole-brain connectivity was characterized from local and global perspectives. Overall lower global efficiency, indicating sub-optimal brain-wide organization and integration, was present in patients with GAD compared to controls. The amygdala and midline cortices showed higher betweenness centrality, reflecting functional dominance of these brain structures. Third, lower betweenness centrality and lower degree emerged for PFC, suggesting weakened inhibitory control. Overall, network organization showed impairments consistent with neurobiological models of GAD (involving amygdala, PFC, and cingulate cortex) and further pointed to an involvement of temporal regions. Such impairments tended to progress over time and predict anxiety symptoms. A graph-analytic approach represents a powerful approach to deepen our understanding of GAD.

Fear processing is differentially affected by lateralized stimulation of carotid baroreceptors

Information processing, particularly of salient emotional stimuli, is influenced by cardiovascular afferent signals. Carotid baroreceptors signal the state of cardiovascular arousal to the brain, controlling blood pressure and heart rate via the baroreflex. Animal studies suggest a lateralization of this effect: Experimental stimulation of the right carotid sinus has a greater impact on heart rate when compared to left-sided stimulation. We tested, in humans, whether the processing of emotional information from faces was differentially affected by right versus left carotid afferents. To achieve so, we used an automated neck suction device to stimulate the carotid mechanoreceptors in the carotid sinus (parasympathetic pathway) synchronously with functional magnetic resonance imaging (fMRI) acquisition whilst participants were engaged in an emotional rating task of fearful and neutral faces. We showed that both right and left carotid stimulation (CS) influenced brain activity within opercular regions, although a stronger activation was observed within left insula during right stimulation compared to left stimulation. As regards the processing of fearful faces, right, but not left carotid stimulation attenuated the perceived intensity of fear, and (albeit to a lesser extent) enhanced intensity ratings of neutral faces. Mirroring the behavioural effects, there was a significant expression-by-stimulation interaction for right carotid stimulation only, when bilateral amygdala responses were attenuated to fear faces and amplified to neutral faces. Individual differences in basal heart rate variability (HRV) predicted the extent to which right carotid stimulation attenuated amygdala responses during fear processing. Our study provides unique evidence for lateralized viscerosensory effects on brain systems supporting emotional processing.

Network attack simulations in Alzheimer's disease: The link between network tolerance and neurodegeneration

The brain structure is a complex network of interconnected regions with specific topological characteristics. Since the disruption of this infrastructure has been linked to brain diseases, a key element to the quest for understanding how such diseases start and spread is to outline the degenerative pattern. In this paper, we explored this aspect using network attack simulation on the structural connectomes of 60 patients among Alzheimers disease (AD) and mild cognitive impairment (MCI) and 30 healthy subjects. We considered different attack strategies and different metrics to evaluate and compare the induced changes between the different groups. We found out that patients and controls share common attack tolerance patterns in the peripheral connections compared to each other, and that hubs played analogous role in the tolerance impact. These results suggest that the spreading pattern of Alzheimers disease does not target specific class of regions.