Barbara Basile

Deontological and altruistic guilt: Evidence for distinct neurobiological substrates

The feeling of guilt is a complex mental state underlying several human behaviors in both private and social life. From a psychological and evolutionary viewpoint, guilt is an emotional and cognitive function, characterized by prosocial sentiments, entailing specific moral believes, which can be predominantly driven by inner values (deontological guilt) or by more interpersonal situations (altruistic guilt). The aim of this study was to investigate whether there is a distinct neurobiological substrate for these two expressions of guilt in healthy individuals. We first run two behavioral studies, recruiting a sample of 72 healthy volunteers, to validate a set of stimuli selectively evoking deontological and altruistic guilt, or basic control emotions (i.e., anger and sadness). Similar stimuli were reproduced in a event‐related functional magnetic resonance imaging (fMRI) paradigm, to investigate the neural correlates of the same emotions, in a new sample of 22 healthy volunteers. We show that guilty emotions, compared to anger and sadness, activate specific brain areas (i.e., cingulate gyrus and medial frontal cortex) and that different neuronal networks are involved in each specific kind of guilt, with the insula selectively responding to deontological guilt stimuli. This study provides evidence for the existence of distinct neural circuits involved in different guilty feelings. This complex emotion might account for normal individual attitudes and deviant social behaviors. Moreover, an abnormal processing of specific guilt feelings might account for some psychopathological manifestation, such as obsessive‐compulsive disorder and depression. Hum Brain Mapp, 2011.

Speech emotion recognition using amplitude modulation parameters and a combined feature selection procedure

Speech emotion recognition (SER) is a challenging framework in demanding human machine interaction systems. Standard approaches based on the categorical model of emotions reach low performance, probably due to the modelization of emotions as distinct and independent affective states. Starting from the recently investigated assumption on the dimensional circumplex model of emotions, SER systems are structured as the prediction of valence and arousal on a continuous scale in a two-dimensional domain. In this study, we propose the use of a PLS regression model, optimized according to specific features selection procedures and trained on the Italian speech corpus EMOVO, suggesting a way to automatically label the corpus in terms of arousal and valence. New speech features related to the speech amplitude modulation, caused by the slowly-varying articulatory motion, and standard features extracted from the pitch contour, have been included in the regression model. An average value for the coefficient of determination R2 of 0.72 (maximum value of 0.95 for fear and minimum of 0.60 for sadness) is obtained for the female model and a value for R2 of 0.81 (maximum value of 0.89 for anger and minimum value of 0.71 for joy) is obtained for the male model, over the seven primary emotions (including the neutral state).

Abnormal Functional Brain Connectivity and Personality Traits in Myotonic Dystrophy Type 1

IMPORTANCE Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy observed in adults, is a genetic multisystem disorder affecting several other organs besides skeletal muscle, including the brain. Cognitive and personality abnormalities have been reported; however, no studies have investigated brain functional networks and their relationship with personality traits/disorders in patients with DM1. OBJECTIVE To use resting-state functional magnetic resonance imaging to assess the potential relationship between personality traits/disorders and changes to functional connectivity within the default mode network (DMN) in patients with DM1. DESIGN, SETTING, AND PARTICIPANTS We enrolled 27 patients with genetically confirmed DM1 and 16 matched healthy control individuals. Patients underwent personality assessment using clinical interview and Minnesota Multiphasic Personality Inventory-2 administration; all participants underwent resting-state functional magnetic resonance imaging. Investigations were conducted at the Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Catholic University of Sacred Heart, and Azienda Ospedaliera San Camillo Forlanini. INTERVENTION Resting-state functional magnetic resonance imaging. MAIN OUTCOMES AND MEASURES Measures of personality traits in patients and changes in functional connectivity within the DMN in patients and controls. Changes in functional connectivity and atypical personality traits in patients were correlated. RESULTS We combined results obtained from the Minnesota Multiphasic Personality Inventory-2 and clinical interview to identify a continuum of atypical personality profiles ranging from schizotypal personality traits to paranoid personality disorder within our DM1 patients. We also demonstrated an increase in functional connectivity in the bilateral posterior cingulate and left parietal DMN nodes in DM1 patients compared with controls. Moreover, patients with DM1 showed strong associations between DMN functional connectivity and schizotypal-paranoid traits. CONCLUSIONS AND RELEVANCE Our findings provide novel biological evidence that DM1 is a clinical condition that also involves an alteration of functional connectivity of the brain. We speculate that these functional brain abnormalities, similarly to frank psychiatric disorders, may account for the atypical personality traits observed in patients with DM1.

Exploration of the relationships between regional grey matter atrophy and cognition in multiple sclerosis

Cognitive impairment may result in significant disability in patients with Multiple Sclerosis (MS). Previous Magnetic Resonance Imaging (MRI) studies on cognition in MS were mainly based on measures of gross brain involvement. This study, using voxel-based morphometry (VBM), aims to investigate associations between the regional distribution of grey matter (GM) damage and cognitive performance in patients with MS. Eighteen MS patients underwent an extensive neuropsychological battery and MRI, including T2-weighted scans and T1-weighted volumes. A group of 18 healthy individuals were also investigated by MRI and served as controls for the VBM. A cross-sectional analysis was first performed, to assess the pattern of regional GM atrophy in MS patients. Then, the impact of regional GM damage on patients’ neuropsychological performance was investigated by multiple regression analyses in the patient group. Correlations between global indexes of brain damage and neuropsychological measures were also assessed for comparison with previous literature. The comparison between MS patients and healthy controls revealed a widespread pattern of regional GM atrophy. Consistent with previous studies, associations were found between neuropsychological scores, and global brain atrophy and T2-lesion volumes. Critically, significant associations were found between scores on the Symbol Digit Modalities test and Long Delay Cued Recall on the California Verbal Learning Test, and regional GM volumes in well localized areas of the prefrontal, parietal, temporal, and insular cortex. This study confirms that global assessments of brain damage correlate with measures of cognitive impairment in MS. Interestingly, VBM contributes to clarify those brain regions that more likely determine the cognitive deficits observed in patients. These findings clarify the pathophysiology of cognitive impairment in MS, and propose measures which could be considered for longitudinal monitoring of patients.

Anatomical brain connectivity can assess cognitive dysfunction in multiple sclerosis

Background: Brain disconnection plays a major role in determining cognitive disabilities in multiple sclerosis (MS). We recently developed a novel diffusion-weighted magnetic resonance imaging (DW-MRI) tractography approach, namely anatomical connectivitity mapping (ACM), that quantifies structural brain connectivity. Objective: Use of ACM to assess structural connectivity modifications in MS brains and ascertain their relationship with the patients’ Paced-Auditory-Serial-Addition-Test (PASAT) scores. Methods: Relapsing–remitting MS (RRMS) patients (n = 25) and controls (n = 25) underwent MRI at 3T, including conventional images, T1-weighted volumes and DW-MRI. Volumetric scans were coregistered to fractional anisotropy (FA) images, to obtain parenchymal FA maps for both white and grey matter. We initiated probabilistic tractography from all parenchymal voxels, obtaining ACM maps by counting the number of streamlines passing through each voxel, then normalizing by the total number of streamlines initiated. The ACM maps were transformed into standard space, for statistical use. Results: RRMS patients had reduced grey matter volume and FA, consistent with previous literature. Also, we showed reduced ACM in the thalamus and in the head of the caudate nucleus, bilaterally. In our RRMS patients, ACM was associated with PASAT scores in the corpus callosum, right hippocampus and cerebellum. Conclusions: ACM opens a new perspective, clarifying the contribution of anatomical brain disconnection to clinical disabilities in MS.

Functional connectivity changes within specific networks parallel the clinical evolution of multiple sclerosis

Background: In multiple sclerosis (MS), the location of focal lesions does not always correlate with clinical symptoms, suggesting disconnection as a major pathophysiological mechanism. Resting-state (RS) functional magnetic resonance imaging (fMRI) is believed to reflect brain functional connectivity (FC) within specific neuronal networks. Objective: RS-fMRI was used to investigate changes in FC within two critical networks for the understanding of MS disabilities, namely, the sensory-motor network (SMN) and the default-mode network (DMN), respectively, implicated in sensory-motor and cognitive functions. Methods: Thirty-four relapsing–remitting (RR), 14 secondary progressive (SP) MS patients and 25 healthy controls underwent MRI at 3T, including conventional images, T1-weighted volumes, and RS-fMRI sequences. Independent component analysis (ICA) was employed to extract maps of the relevant RS networks for every participant. Group analyses were performed to assess changes in FC within the SMN and DMN in the two MS phenotypes. Results: Increased FC was found in both networks of MS patients. Interestingly, specific changes in either direction were observed also between RR and SP MS groups. Conclusions: FC changes seem to parallel patients’ clinical state and capability of compensating for the severity of clinical/cognitive disabilities.

Abnormal processing of deontological guilt in obsessive–compulsive disorder

Guilt plays a significant role in the occurrence and maintenance of obsessive–compulsive disorder (OCD). Two major types of guilt have been identified: one deriving from the transgression of a moral rule (deontological guilt DG), another (altruistic guilt AG), relying on the assumption of having compromised a personal altruistic goal. Clinical evidence suggests that OCD patients are particularly sensitive to DG, but not AG. In this functional magnetic resonance imaging (fMRI) study, we investigated brain response of OCD patients while processing DG and AG stimuli. A previously validated fMRI paradigm was used to selectively evoke DG and AG, and anger and sadness, as control emotions in 13 OCD patients and 19 healthy controls. Patients’ behavioral results showed a prominent attitude to experience guilt, compared to controls, while accomplishing task. fMRI results revealed that patients have reduced activation in the anterior cingulate (ACC) and frontal gyrus when experiencing guilt, regardless of its specific type (DG or AG). When separately considering each type of guilt (against each of its control), patients showed decreased activation in the ACC, the insula and the precuneus, for DG. No significant differences were observed between groups when processing AG, anger or sad stimuli. This study provides evidence for an abnormal processing of guilt, and specifically DG, in OCD patients. We suggest that decreased activation may reflect patients’ cerebral efficiency, which derives from their frequent exposure to guilty feelings (“neural efficiency hypothesis”). In conclusion, our study confirms a selective abnormal processing of guilt, and specifically DG, in OCD.

Effect of Parasympathetic Stimulation on Brain Activity During Appraisal of Fearful Expressions

Autonomic nervous system activity is an important component of human emotion. Mental processes influence bodily physiology, which in turn feeds back to influence thoughts and feelings. Afferent cardiovascular signals from arterial baroreceptors in the carotid sinuses are processed within the brain and contribute to this two-way communication with the body. These carotid baroreceptors can be stimulated non-invasively by externally applying focal negative pressure bilaterally to the neck. In an experiment combining functional neuroimaging (fMRI) with carotid stimulation in healthy participants, we tested the hypothesis that manipulating afferent cardiovascular signals alters the central processing of emotional information (fearful and neutral facial expressions). Carotid stimulation, compared with sham stimulation, broadly attenuated activity across cortical and brainstem regions. Modulation of emotional processing was apparent as a significant expression-by-stimulation interaction within left amygdala, where responses during appraisal of fearful faces were selectively reduced by carotid stimulation. Moreover, activity reductions within insula, amygdala, and hippocampus correlated with the degree of stimulation-evoked change in the explicit emotional ratings of fearful faces. Across participants, individual differences in autonomic state (heart rate variability, a proxy measure of autonomic balance toward parasympathetic activity) predicted the extent to which carotid stimulation influenced neural (amygdala) responses during appraisal and subjective rating of fearful faces. Together our results provide mechanistic insight into the visceral component of emotion by identifying the neural substrates mediating cardiovascular influences on the processing of fear signals, potentially implicating central baroreflex mechanisms for anxiolytic treatment targets.

White Matter Damage Along the Uncinate Fasciculus Contributes to Cognitive Decline in AD and DLB

This study investigates the patho-physiological implications of the uncinate fasciculus (UF) in the two most common forms of dementia, namely Alzheimers disease (AD) and dementia with Lewy bodies (DLB). Forty-five consecutive patients diagnosed with either probable AD or DLB, and 16 individuals with amnesic mild cognitive impairment (a-MCI) were investigated using diffusion tensor MRI. Thirteen healthy subjects (HS) were also studied as controls. In each subject, the UF was bilaterally reconstructed by probabilistic tractography. From each UF, macroscopic volume and correspondent fractional anisotropy (FA) (an index of microscopic white matter integrity) were derived for the whole tract, and for the frontal and temporal portion of the UF. No significant between-group volumetric differences were found. In contrast, FA values from the UF were reduced bilaterally in patients with dementia (either AD or DLB) compared to HS. In addition, patients with AD showed reduced FA values compared to those with a-MCI. No significant FA difference was found between AD and DLB patients, nor between a-MCI and HS. Finally, in all patients, UF FA values were associated with neuropsychological scores at tests exploring memory and executive functions. This study indicates that the UF is remarkably damaged in patients at the stage of dementia, independently from the diagnostic form. Moreover, this UF damage seems to be driven by temporal involvement in AD, for which a prodromal stage (a-MCI) is defined.

Direct stimulation of the autonomic nervous system modulates activity of the brain at rest and when engaged in a cognitive task

The effect of autonomic perturbation (AP) on the central nervous system functioning is still largely unknown. Using an automated neck suction device to stimulate the carotid mechanoreceptors in the carotid sinus (parasympathetic pathway), operated synchronously with functional magnetic resonance imaging (fMRI) acquisition, we investigated the effects of AP on the activity of the brain at rest and when engaged in a visuo‐spatial attention task. ECG was always recorded to index changes in autonomic function. At rest, AP induced increased activation in the insula and in the amygdala, which have been previously associated with the autonomic control and emotion processing, as well as in the caudate nucleus and in the medial temporal cortex, both implicated in cognitive functions. Despite a preserved performance during visuo‐spatial attention task, AP induced increased reaction times and a positive modulation on the activation of the right posterior parietal cortex, the occipital cortex, the periaquiductal gray, and nuclei of the brainstem. We speculate that this modulation of brain activity represents, at different anatomical levels, a compensation mechanism to maintain cognitive efficiency under parasympathetic stimulation, which is traditionally considered as the system for energy regain and storage. In conclusion, this study provides the first evidence of a dynamic interaction between AP and higher level functions in humans. Hum Brain Mapp, 2013.