Papers by Prof. Franco Cauda MSc PhD
Medication-overuse headache (MOH) is a secondary form of headache related to the overuse of tript... more Medication-overuse headache (MOH) is a secondary form of headache related to the overuse of triptans, analgesics and other acute headache medications. It is believed that MOH and substance addiction share some similar pathophysiological mechanisms. In this study we examined the whole brain resting state functional connectivity of the dorsal and ventral striatum in 30 patients (15 MOH and 15 non-MOH patients) to investigate if classification algorithms can successfully discriminate between MOH and non-MOH patients on the basis of the spatial pattern of resting state functional connectivity of the dorsal and ventral striatal region of interest. Our results indicated that both nucleus accumbens and dorsal rostral putamen functional connectivity could discriminate between MOH and non-MOH patients, thereby providing possible support to two interpretations. First, that MOH patients show altered reward functionality in line with drug abusers (alterations in functional connectivity of the nucleus accumbens). Second, that MOH patients show inability to break habitual behavior (alterations in functional connectivity of the dorsal striatum). In conclusion, our data showed that MOH patients were characterized by an altered functional connectivity of motivational circuits at rest. These differences could permit the blind discrimination between the two conditions using classification algorithms. Considered overall, our findings might contribute to the development of novel diagnostic measures.
Background: DYT1 mutation is characterized by focal to generalized dystonia and incomplete penetr... more Background: DYT1 mutation is characterized by focal to generalized dystonia and incomplete penetrance. To explore the complex perturbations in the different neural networks and the mutual interactions among them, we studied symptomatic and asymptomatic DTY1 mutation carriers by resting-state functional MRI. Methods: A total of 7 symptomatic DYT1, 10 asymptomatic DYT1, and 26 healthy controls were considered. Resting-state functional MRI (Oxford Centre for Functional MRI of the Brain) [FMRIB] Software Library) (FSL) MELODIC, dual regression, (as a toolbox of FSL, with Nets is referred to "networks") (FSLNets) (http:// fsl.fmrib.ox.ac.uk/fsl/fslwiki/FSLNets) was performed on 9 resting-state neural networks. Results: DYT1 mutation signature (symptomatic DYT1 and asymptomatic DYT1) was characterized by increased connectivity in the dorsal attention network and in the left fronto-parietal network. Functional correlates of symptomatic DYT1 patients (symptomatic DYT1 vs healthy controls) showed increased connectivity in the sensorimotor network. Discussion: This study argues that DYT1 dystonia is a network disorder, with crucial nodes in sensory-motor integration of posterior parietal structures. A better characterization of cortical networks involved in dystonia is crucial for possible neurophysiological therapeutic interventions. V
Schizophrenia spectrum disorder (SCZD), autism spectrum disorder (ASD), and obsessive-compulsive ... more Schizophrenia spectrum disorder (SCZD), autism spectrum disorder (ASD), and obsessive-compulsive spectrum disorder (OCSD) are considered as three separate psychiatric conditions with, supposedly, different brain alterations patterns. From a neuroimaging perspective, this meta-analytic study aimed to address whether this nosographical differentiation is actually supported by different brain patterns of gray matter (GM) or white matter (WM) morphological alterations. We explored two possibilities: (a) to find out whether GM alterations are specific for SCZD, ASD, and OCSD; and (b) to associate the identified brain alteration patterns with cognitive dysfunctions by means of an analysis of lesion decoding. Our analysis reveals that these psychiatric spectra do not present clear distinctive patterns of alterations; rather, they all tend to be distributed in two alteration clusters. Cluster 1, which is more specific for SCZD, includes the anterior insular, anterior cingulate cortex, ventromedial prefrontal cortex, and frontopolar areas, which are parts of the cognitive control system. Cluster 2, which is more specific for OCSD, presents occipital, temporal, and parietal alteration patterns with the involvement of sensorimotor, premotor, visual, and lingual areas, thus forming a network that is more associated with the auditory-visual, auditory, premotor visual somatic functions. In turn, ASD appears to be uniformly distributed in the two clusters. The three spectra share a significant set of alterations. Our new approach promises to provide insight into the understanding of psychiatric conditions under the aspect of a common neurobiological substrate, possibly related to neuroinflammation during brain development.
Although mindfulness meditation has been practiced in the East for more than two millennia, Weste... more Although mindfulness meditation has been practiced in the East for more than two millennia, Western scientific research and healthcare programs have only recently drawn their attention to it. Basically, the concept of mindfulness hinges on focusing on one's own awareness at the present moment. In this review we analyze different hypotheses about the functioning and the cerebral correlates of mindfulness meditation. Since mindfulness is strictly associated with a particular state of consciousness, we also examine some of the most relevant theories that have been proposed as accounts of consciousness. Finally, we suggest that consciousness and mindfulness meditation can be integrated within a neuroscientific perspective, by identifying the brain areas which seem to play an essential role in both, namely the anterior cingulate cortex, posterior cingulate cortex, insula and thalamus.
The cerebellum has been traditionally considered a sensory-motor structure, but more recently has... more The cerebellum has been traditionally considered a sensory-motor structure, but more recently has been related to other cognitive and affective functions. Previous research and meta-analytic studies suggested that it could be involved in pain processing. Our aim was to distinguish the functional networks subserved by the cerebellum during pain processing. We used functional magnetic resonance imaging (fMRI) on 12 subjects undergoing mechanical pain stimulation and resting state acquisition. For the analysis of data, we used fuzzy cmean to cluster cerebellar activity of each participant during nociception. The mean time courses of the clusters were used as regressors in a general linear model (GLM) analysis to explore brain functional connectivity (FC) of the cerebellar clusters. We compared our results with the resting state FC of the same cluster and explored with meta-analysis the behavior profile of the FC networks. We identified three significant clusters: cluster V, involving the culmen and quadrangular lobules (vermis IV-V, hemispheres IV-V-VI); cluster VI, involving the posterior quadrangular lobule and superior semilunar lobule (hemisphere VI, crus 1, crus 2), and cluster VII, involving the inferior semilunar lobule (VIIb, crus1, crus 2). Cluster V was more connected during pain with sensory-motor areas, cluster VI with cognitive areas, and cluster VII with emotional areas. Our results indicate that during the application of mechanical punctate stimuli, the cerebellum is not only involved in sensory functions but also with areas typically associated with cognitive and affective functions. Cerebellum seems to be involved in various aspects of nociception, reflecting the multidimensionality of pain perception.
It has been suggested that the Rorschach human movement (M) response could be associated with an ... more It has been suggested that the Rorschach human movement (M) response could be associated with an embodied simulation mechanism mediated by the mirror neuron system (MNS). To date, evidence for this hypothesis comes from two electroencephalogram studies and one repetitive transcranial magnetic stimulation study. To provide additional data on this topic, the Rorschach was administered during fMRI to a sample of 26 healthy adult volunteers. Activity in MNSrelated brain areas temporally associated with M responses was compared with such activity for other, non-M Rorschach responses. Data analyses focused on MNS regions of interest identified by Neurosynth, a web-based platform for large scale, automated meta-analysis of fMRI data. Consistent with the hypothesis that M responses involve embodied simulation and MNS activity, univariate region of interest analyses showed that production of M responses associated with significantly greater activity in MNS-related brain areas when compared with non-M Rorschach responses. This finding is consistent with the traditional interpretation of the M code.
Introduction. The present study was intended to evaluate the effects of a rehabilitative training... more Introduction. The present study was intended to evaluate the effects of a rehabilitative training, the Cognitive Pragmatic Treatment (CPT), aimed at improving communicative-pragmatic abilities and the related cognitive components, on the cerebral modifications of a single case patient diagnosed with schizophrenia. Methods. The patient underwent two functional magnetic resonance imaging (fMRI) sessions, before and after the treatment. In order to assess brain changes, we calculated the Amplitude of Low Frequency Fluctuation (ALFF) index of the resting-state fMRI signal, which is interpreted as reflecting the intensity of the spontaneous regional activity of the brain. Behavioural measures of the patient's communicative performance were also gathered before and after training and at follow-up. Results. The patient improved his communicative performance in almost all tests. Posttraining stronger ALFF signal emerged in the superior, inferior, and medial frontal gyri, as well as the superior temporal gyri. Conclusions. Even if based on a single case study, these preliminary results show functional changes at the cerebral level that seem to support the patient's behavioural improvements.
Recently, a lot of effort has been made to ground Rorschach interpretations to their evidence bas... more Recently, a lot of effort has been made to ground Rorschach interpretations to their evidence base. To date, however, no studies have yet described, via fMRI, what brain areas get involved when one takes the Rorschach. To fill this gap in the literature, we administered the ten-inkblot stimuli to 26 healthy volunteers during fMRI. Analysis of BOLD signals revealed that, compared to fixating a cross, looking at the Rorschach inkblots while thinking of what they might be associated with higher temporo-occipital and fronto-parietal activations, and with greater activity in some small, sub-cortical regions included in the limbic system. These findings are in line with the traditional conceptualization of the test, as they suggest that taking the Rorschach involves (a) highlevel visual processing, (b) top-down as well as bottom-up attentional processes, and (c) perception and processing of emotions and emotional memories.
In this research we have analyzed functional magnetic resonance imaging (fMRI) signals of differe... more In this research we have analyzed functional magnetic resonance imaging (fMRI) signals of different networks in the brain under resting state condition. To such end, the dynamics of signal variation, have been conceived as a stochastic motion, namely it has been modelled through a generalized Langevin stochastic differential equation, which combines a deterministic drift component with a stochastic component where the Gaussian noise source has been replaced with α-stable noise. The parameters of the deterministic and stochastic parts of the model have been fitted from fluctuating data. Results show that the deterministic part is characterized by a simple, linear decreasing trend, and, most important, the α-stable noise, at varying characteristic index α, is the source of a spectrum of activity modes across the networks, from those originated by classic Gaussian noise (α = 2), to longer tailed behaviors generated by the more general Lévy noise (1 α < 2). Lévy motion is a specific instance of scale-free behavior, it is a source of anomalous diffusion and it has been related to many aspects of human cognition, such as information foraging through memory retrieval or visual exploration. Finally, some conclusions have been drawn on the functional significance of the dynamics corresponding to different α values.
It was recently suggested that in brain disorders neuronal alterations does not occur randomly, b... more It was recently suggested that in brain disorders neuronal alterations does not occur randomly, but tend to form patterns that resemble those of cerebral connectivity. Following this hypothesis, we studied the network formed by co-altered brain regions in patients with chronic pain. We used a meta-analytical network approach in order to: i) find out whether the neuronal alterations distribute randomly across the brain; ii) find out (in the case of a non-random pattern of distribution) whether a disease-specific pattern of brain co-alterations can be identified and characterized in terms of altered areas (nodes) and propagation links between them (edges); iii) verify whether the co-alteration pattern overlaps with the pattern of functional connectivity; iv) describe the topological properties of the co-alteration network and identify the highly connected nodes that are supposed to have a pre-eminent role in the diffusion timing of neuronal alterations across the brain. Our results indicate that: i) gray matter (GM) alterations do not occur randomly; ii) a symptom-related pattern of structural co-alterations can be identified for chronic pain; iii) this co-alteration pattern resembles the pattern of brain functional connectivity; iv) within the co-alteration network a set of highly connected nodes can be identified. This study provides further support to the hypothesis that neuronal alterations may spread according to the logic of a network-like diffusion suggesting that this type of distribution may also apply to chronic pain.
The quest to characterize the neural signature distinctive of different basic emotions has recent... more The quest to characterize the neural signature distinctive of different basic emotions has recently come under renewed scrutiny. Here we investigated whether facial expressions of different basic emotions modulate the functional connectivity of the amygdala with the rest of the brain. To this end, we presented seventeen healthy participants (8 females) with facial expressions of anger, disgust, fear, happiness, sadness and emotional neutrality and analyzed amygdala's psychophysiological interaction (PPI). In fact, PPI can reveal how interregional amygdala communications change dynamically depending on perception of various emotional expressions to recruit different brain networks, compared to the functional interactions it entertains during perception of neutral expressions. We found that for each emotion the amygdala recruited a distinctive and spatially distributed set of structures to interact with. These changes in amygdala connectional patters characterize the dynamic signature prototypical of individual emotion processing, and seemingly represent a neural mechanism that serves to implement the distinctive influence that each emotion exerts on perceptual, cognitive, and motor responses. Besides these differences, all emotions enhanced amygdala functional integration with premotor cortices compared to neutral faces. The present findings thus concur to reconceptualise the structure-function relation between brain-emotion from the traditional one-to-one mapping toward a network-based and dynamic perspective.
Mirror neurons have been proposed to underlie humans' ability to understand others' actions and i... more Mirror neurons have been proposed to underlie humans' ability to understand others' actions and intentions. Despite 2 decades of research, however, the exact computational and neuronal mechanisms implied in this ability remain unclear. In the current study, we investigated whether, in the absence of contextual cues, regions considered to be part of the human mirror neuron system represent intention from movement kinematics. A total of 21 participants observed reach-to-grasp movements, performed with either the intention to drink or to pour while undergoing functional magnetic resonance imaging. Multivoxel pattern analysis revealed successful decoding of intentions from distributed patterns of activity in a network of structures comprising the inferior parietal lobule, the superior parietal lobule, the inferior frontal gyrus, and the middle frontal gyrus. Consistent with the proposal that parietal regions play a key role in intention understanding, classifier weights were higher in the inferior parietal region. These results provide the first demonstration that putative mirror neuron regions represent subtle differences in movement kinematics to read the intention of an observed motor act.
Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) are the most implemented methodo... more Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) are the most implemented methodologies to detect alterations of both gray and white matter (WM). However, the role of WM in mental disorders is still not well defined. We aimed at clarifying the role of WM disruption in schizophrenia and at identifying the most frequently involved brain networks. A systematic literature search was conducted to identify VBM and DTI studies focusing on WM alterations in patients with schizophrenia compared to control subjects. We selected studies reporting the
A targeted training program for the rehabilitation of communicative abilities-Cognitive Pragmatic... more A targeted training program for the rehabilitation of communicative abilities-Cognitive Pragmatic Treatment (CPT)-has been developed and previously tested on a sample of patients with traumatic brain injury (TBI), whose performance was found to have improved. Since cortical plasticity has been recognized as the main mechanism of functional recovery, we investigated whether and how behavioral improvements following the training program are accompanied by brain modifications. Eight TBI patients took part in the training program and were behaviorally assessed pre-and post-treatment; six of these patients were also evaluated with pre-and post-treatment resting state (rs) functional magnetic resonance imaging (fMRI). At the end of the rehabilitation program patients showed improvement in overall communicative performance, in both comprehension and production tasks. A follow-up retest revealed the stability of these results 3 months after completing the training program. At the brain level, we found significant increases in the amplitude of low frequency fluctuation (ALFF) index in the bilateral precentral gyrus, in the right middle and superior temporal gyri, in the right cingulate gyrus, and in the left inferior parietal lobule. We discuss these differences of brain activity in terms of their possible contribution to promoting recovery.
Here we investigate whether systems that minimize prediction error e.g. predictive coding, can al... more Here we investigate whether systems that minimize prediction error e.g. predictive coding, can also show creativity, or on the contrary, prediction error minimization unqualifies for the design of systems that respond in creative ways to non-recurrent problems. We argue that there is a key ingredient that has been overlooked by researchers that needs to be incorporated to understand intelligent behavior in biological and technical systems. This ingredient is boredom. We propose a mathematical model based on the Black-Scholes-Merton equation which provides mechanistic insights into the interplay between boredom and prediction pleasure as the key drivers of behavior.
It was recently suggested that in brain disorders neuronal alterations does not occur randomly, b... more It was recently suggested that in brain disorders neuronal alterations does not occur randomly, but tend to form patterns that resemble those of cerebral connectivity. Following this hypothesis, we studied the network formed by co-altered brain regions in patients with chronic pain. We used a meta-analytical network approach in order to: i) find out whether the neuronal alterations distribute randomly across the brain; ii) find out (in the case of a non-random pattern of distribution) whether a disease-specific pattern of brain co-alterations can be identified and characterized in terms of altered areas (nodes) and propagation links between them (edges); iii) verify whether the co-alteration pattern overlaps with the pattern of functional connectivity; iv) describe the topological properties of the co-alteration network and identify the highly connected nodes that are supposed to have a pre-eminent role in the diffusion timing of neuronal alterations across the brain. Our results indicate that: i) gray matter (GM) alterations do not occur randomly; ii) a symptom-related pattern of structural co-alterations can be identified for chronic pain; iii) this co-alteration pattern resembles the pattern of brain functional connectivity; iv) within the co-alteration network a set of highly connected nodes can be identified. This study provides further support to the hypothesis that neuronal alterations may spread according to the logic of a network-like diffusion suggesting that this type of distribution may also apply to chronic pain.
Gray matter alterations are typical features of brain disorders. However, they do not impact on t... more Gray matter alterations are typical features of brain disorders. However, they do not impact on the brain randomly. Indeed, it has been suggested that neuropathological processes can selectively affect certain assemblies of neurons, which typically are at the center of crucial functional networks. Because of their topological centrality, these areas form a core set that is more likely to be affected by neuropathological processes. In order to identify and study the pattern formed by brain alterations in patients' with Alzheimer's disease (AD), we devised an innovative meta-analytic method for analyzing voxel-based morphometry data. This methodology enabled us to discover that in AD gray matter alterations do not occur randomly across the brain but, on the contrary, follow identifiable patterns of distribution. This alteration pattern exhibits a network-like structure composed of coaltered areas that can be defined as coatrophy network. Within the coatrophy network of AD, we were able to further identify a core subnetwork of coaltered areas that includes the left hippocampus, left and right amygdalae, right parahippocampal gyrus, and right temporal inferior gyrus. In virtue of their network centrality, these brain areas can be thought of as pathoconnectivity hubs.
By means of a novel methodology that can statistically derive patterns of co-alterations distribu... more By means of a novel methodology that can statistically derive patterns of co-alterations distribution from voxel-based morphological data, this study analyzes the patterns of brain alterations of three important psychiatric spectra-that is, schizophrenia spectrum disorder (SCZD), autistic spectrum disorder (ASD), and obsessive-compulsive spectrum disorder (OCSD). Our analysis provides five important results. First, in SCZD, ASD, and OCSD brain
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Papers by Prof. Franco Cauda MSc PhD