Structural and functional MRI study in mentally ill persons considered socially dangerous with diminished penal responsibility

La complessa relazione tra malattia mentale e criminalità rappresenta un tema di concreta rilevanza sociale, dibattuto da anni ma sempre di grande attualità. Secondo il codice penale, è considerato “socialmente pericoloso” il soggetto autore di reato, anche se non imputabile per vizio totale o parziale di mente, che abbia una elevata probabilità di recidiva del reato. Per questo motivo la prevenzione delle azioni socialmente pericolose riveste un ruolo di fondamentale importanza giuridica e sociale. In questo contesto la psichiatria forense si occupa delle questioni che sorgono all’interfaccia tra psichiatria e giurisprudenza, con l’obiettivo principale di evidenziare lo stato di salute mentale dei soggetti che commettono un reato attraverso una perizia psichiatrica. La disciplina neuroradiologica, grazie anche all’utilizzo di tecniche avanzate di analisi delle immagini, si pone oggi come strumento di valido ausilio nella valutazione clinica dei pazienti psichiatrici e può supportare gli sforzi congiunti di psichiatri e giuristi per studiare la relazione tra malattia mentale e criminalità. L’obiettivo di questo progetto di dottorato è stato quello di effettuare uno studio volumetrico della sostanza grigia cerebrale attraverso un esame di Risonanza Magnetica (RM) su un gruppo di soggetti autori di reato, considerati non imputabili al momento del fatto per vizio totale o parziale di mente, detenuti nella REMS dell’ASL Rm5 e considerati socialmente pericolosi. I risultati dell’analisi volumetrica sono stati confrontati con un gruppo di controllo, comparabile per età e sesso. E’stata inoltre effettuata un’analisi della connettività funzionale cerebrale a riposo (resting-state functional MRI) con l’intento di indagare i network cerebrali alla base del comportamento morale, dell’attribuzione della salienza e dei processi di ricompensa, confrontando sempre i risultati con un gruppo di controllo. Nel gruppo sperimentale sono stati inclusi 13 individui destrorsi (età media: 44 ± 7 anni) detenuti nella REMS dell’ASL Rm5 con disturbo dello spettro psicotico (schizofrenia, disturbo bipolare con caratteristiche psicotiche, disturbo schizo-affettivo, disturbi deliranti), che hanno commesso crimini violenti (omicidi, tentati omicidi, aggressioni e violenze domestiche) e che sono stati dichiarati socialmente pericolosi dall’autorità giudiziaria a causa dell’ alto rischio di recidiva criminale. I dati di RM sono stati acquisiti su un magnete 3 Tesla (Verio, Siemens) dotato di una bobina a 12 canali, utilizzando sequenze volumetriche T13D e sequenze BOLD eco-planari (EPI). Nello studio I abbiamo eseguito un’analisi della volumetria cerebrale con tecnica VBM (Voxel-based morphometry) utilizzando il Computational Anatomy Toolbox (CAT12) del software Statistical Parametric Mapping (SPM12). Abbiamo riscontrato come il volume della sostanza grigia cerebrale del gruppo sperimentale fosse significativamente ridotto, rispetto ai controlli, a livello della corteccia insulare bilaterale, nel giro temporale superiore (STG) dell’emisfero sinistro e nel giro fusiforme dell’emisfero destro. Abbiamo infine eseguito un’analisi di correlazione tra la gravità dei sintomi psichiatrici e le regioni con volume corticale ridotto. I cluster di volume a livello di STG e insula sinistra sono risultati essere significativamente correlati alla gravità dei sintomi espressa dalla scala di valutazione BPRS (Brief Psychiatric Rating Scale). Nello studio II abbiamo esaminato la connettività cerebrale a riposo nelle 19 regioni selezionate “a priori” sulla base della letteratura che risultassero coinvolte nella morale, nell’ attribuzione della salienza e nei processi di ricompensa. L’analisi è stata effettuata utilizzando il software CONN v. 18a, sulla piattaforma Matlab. Abbiamo documentato una ridotta connettività tra le regioni del sistema limbico, come il nucleo accumbens e l’amigdala, ed aumentata connettività nello striato dorsale, tra il nucleo accumbens e la corteccia cingolata posteriore, tra corteccia fronto-orbitale e gangli della base e tra corteccia cingolata anteriore e amigdala. Sulla base di questi risultati ipotizziamo che l’alterata connettività in queste specifiche aree possa rappresentare la modificazione del comportamento in senso maladattativo degli individui del gruppo sperimentale, in termini di alterata risposta emotiva circa le proprie violazioni morali o di mancanza di empatia verso gli altri al fine di ottenere vantaggi personali o riguardo al controllo dell’impulsività. Nonostante la bassa numerosità campionaria non consenta di approdare a conclusioni definitive, questo studio cerca di approfondire i correlati neurali degli individui autori di reato con ridotta responsabilità penale e socialmente pericolosi al fine di fornire un eventuale strumento di ausilio nella valutazione di questa particolare categoria di persone, con importanti risvolti giuridici ed etici oltre che nella pianificazione e nello sviluppo del trattamento di questi pazienti durante la loro permanenza nelle REMS.The relation between mental illness and criminality is a relevant social issue that has been debated over the years. Socially dangerous actions committed by mentally ill patients often have severe consequences, which is why much public attention is directed toward the prevention of these actions by these individuals. Modern neuroimaging investigations support the joint efforts of psychiatrists and lawyers to study the relationship between psychiatric illness and criminality. The overall aim of this PhD project was to investigate differences in cortical GM volumes of this population, compared to a control group of healthy non-offender participants, using a VBM analysis of structural MRI. We also decided to investigate brain networks underpinning moral behaviour, salience attribution and reward processes performing a functional MRI at resting-state. Experimental Group (EG) included 13 right-handed individuals (mean age: 44 ± 7 yrs) who committed violent crimes (homicides, attempted homicides, aggressions, and domestic violence), had a diagnosis included in the psychotic spectrum (schizophrenia, bipolar disorder with psychotic features, schizoaffective disorder, delusional disorders) and were declared socially dangerous by the judicial authority due to a high risk of criminal recidivism. All subjects of the EG were institutionalized in the REMS psychiatric unit of ASL RM5 (Rome, Italy) for no longer than two years. Thirteen healthy right-handed men, who had never received a psychiatric diagnosis, undergone any psychiatric treatment, or been convicted of any crime were included in the control group (CG) (mean age: 38 ± 11yrs). MRI data were acquired using a 3 Tesla Siemens imaging system (Siemens, Verio, Erlangen, Germany) equipped with a 12-channel head coil. Structural scans of the brain were acquired for each participant using a T1-weighted three dimensionals sagittal magnetization-prepared rapid gradient echo sequence. Resting state functional (rs-fMRI) data were collected while participants lay still and awake, with eyes closed using T2*-weighted gradient-echo echo-planar functional images (EPIs). In study I we performed a voxel-based morphometry (VBM) analyses on participants’ T1-weighted structural images using Computational Anatomy Toolbox (CAT12), which runs within SPM12. We found that total cerebral GM volume was significantly reduced in EG in specific regions within the bilateral insular cortex compared to controls. We also found a reduced GM volume in the superior temporal gyrus (STG) of left hemisphere and in the fusiform gyrus of the right hemisphere. We finally performed a correlation analyses between psychiatric symptoms and regions with reduced GM volume. The clusters in STG and insula of left hemisphere significantly correlated with the gravity of symptoms expressed by the BPRS (Brief Psychiatric Rating Scale). In study II, temporal correlations of the resting-state BOLD signal time series were examined between nineteen seed regions that we selected “a priori” among those known to be involved in moral judgment salience attribution and reward processes. Analysis was performed using the software CONN v. 18a, running in Matlab. Our results documented reduced connectivity in limbic regions like the nucleus accumbens and the amiygdala and augmented connectivity within the dorsal striatum, between nucleus accumbens and the posterior cingulate cortex, between fronto- orbitalis cortex and basal ganglia and anterior cingulate cortex and amygdala. We suggest that dysregulation in these areas reflects the maladaptive behavior of socially dangerous subjects in terms of an altered emotional response to their own moral violations and a lack of empathy for others when making personal desire-oriented decisions. While the small sample size does not allow definitive conclusions to be reached, the present study sheds some light on the neural correlates of this specific population, which deserves further attention due to their theoretical and clinical implications. A further understanding of the neural basis of risk evaluation in mentally ill persons with a history of violence who are judged not criminally responsible could aid in forensic assessment and treatment development

PROGETTO DI UNA MACCHINA A CONTROLLO NUMERICO PER L'APPLICAZIONE DI FILM PLASTICO SU SUOLA

Il seguente lavoro di tesi costituisce il progetto di una macchina a controllo numerico per l’applicazione di film plastico su suole. E’ stata progettata una macchina, denominata P.94, a doppia postazione. Le suole vengono posizionate su una postazione dove è stato precedentemente svolto il film plastico e quindi tagliate nella stessa posizione nella quale sono state caricate. Per ridurre i costi della macchina è stata scelta una soluzione semiautomatica con carico e scarico delle suole manuali. Il progetto della meccanica della P.94 è stato diviso in tre nuclei fondamentali: sistema di avvolgimento, sistema di taglio e pressatura e sistema di centraggio. Per il controllo della testina di taglio le specifiche richiedevano che il profilo delle suole venisse seguito con un errore massimo di 2 mm in un tempo tale che l’operatore potesse scaricare la seconda postazione, riavvolgere il film e caricare le nuove suole senza tempi di attesa. E’ stato quindi progettato un sistema di controllo composto da diversi controllori con scopi differenti: un controllore dinamico, più interno, che opera sul modello dinamico ed ha come riferimenti le velocità angolari richieste ai motori e come uscite le tensioni di armatura da fornire ai motori stessi e un controllore cinematico, più esterno, che opera sul modello solo cinematico della testina di taglio e la stabilizza sul percorso assegnato. Le specifiche richieste al controllore dinamico riguardavano solamente la velocità di convergenza; per rispettare questo tipo di specifica è stato sufficiente un controllore di tipo PID. Il controllore cinematico invece è risultato essere più complesso ed ha richiesto uno studio più accurato. In particolare sono stati progettati tre controllori cinematici: due PID per gli spostamenti in rapido dalla posizione di riposo alle Postazioni 1 e 2, ed un controllore progettato a partire dalla cinematica della testina di taglio per la fase di taglio. L’intero sistema di controllo è stato poi campionato e sono stati valutati gli effetti di tale trasformazione. E’ stata infine progettata l’interfaccia utente, per consentire una semplice ed intuitiva interazione tra operatore e macchina

Wine tasting: a neurophysiological measure of taste and olfaction interaction in the experience

In the last years have been provided evidences of sensory–sensory connectivity and influences of one modality over primary sensory cortex of another, a phenomena called crossmodality. Typically, for the wine tasting, sommeliers in addition to the use of the gustation, by the introduction of the wine into the mouth, employ the stimulation of the olfactory system both through a direct olfactory stimulation (by the nose) and a retro-nasal pathway (inhaling air while swirling the wine around in the mouth). Aim of the present study was to investigate the reaction to the wine gustation with and without the direct olfactory contribution, through an electroencephalographic index of approach or withdrawal (AW) motivation, and an autonomic index (Emotional Index – EI), deriving from the matching of heart rate and galvanic skin response activity and considered an indicator of emotional involvement. Results showed a statistically significant increase of the EI values in correspondence of wine tasting with the olfactory component (p<0.01) in comparison to the tasting without the direct olfactory contribution, and a trend of greater approach attitude was reported for the same condition. Data suggest an interaction of the two sensory modalities influencing the emotional and the cognitive aspects of wine tasting experience in a non-expert sampl

The choice of gadolinium-based contrast agents: a radiologist’s responsibility between pharmaceutical equivalence and bioethical issues

Contrast Agents (CA) are among the most commonly prescribed drugs worldwide, and are used, with a variety of techniques, to increase and intensify the differences between body tissues and to help radiologist make diagnoses in a fast and precise way. In recent decades, advancements in research have resulted in significant improvements in their composition, and have made them safer and better-tolerated by patients; this notwithstanding, although the currently available CA are generally considered to be safe, their use is not completely without risk. The use of CA faces the radiologist with economic considerations, bioethical dilemmas, and possible profiles of professional responsibility. In fact, to achieve the best results in diagnostic imaging, radiologists have to focus on making an appropriate choice of CA, in consideration of efficacy, safety and appropriateness. Moreover, besides by cost/benefit models widely introduced in health management, radiologists are also influenced by their responsibility of appropriate use for the various diagnostic tests and, finally, the choice of best CA to utilise for each individual patient. Thus, the dilemma of choosing between the best and the most cost-effective tests and procedures is occurring more frequently every day. Different variables, such as the patient, examinations, and technology available, can affect the choice of CA in terms of obtaining the highest diagnostic quality, minimum impact on higher-risk patients, and optimisation of used volumes and injection flow

Gender and Age Related Effects While Watching TV Advertisements: An EEG Study

The aim of the present paper is to show how the variation of the EEG frontal cortical asymmetry is related to the general appreciation perceived during the observation of TV advertisements, in particular considering the influence of the gender and age on it. In particular, we investigated the influence of the gender on the perception of a car advertisement (Experiment 1) and the influence of the factor age on a chewing gum commercial (Experiment 2). Experiment 1 results showed statistically significant higher approach values for the men group throughout the commercial. Results from Experiment 2 showed significant lower values by older adults for the spot, containing scenes not very enjoyed by them. In both studies, there was no statistical significant difference in the scene relative to the product offering between the experimental populations, suggesting the absence in our study of a bias towards the specific product in the evaluated populations. These evidences state the importance of the creativity in advertising, in order to attract the target population

The relationships between vitamin K and cognition: a review of current evidence

Vitamin K is a fat-soluble nutrient discovered in 1935 and its role in blood coagulation has been thoroughly explored. In recent years, studies conducted in vitro and on animals highlighted vitamin K involvement in brain cells development and survival. In particular, vitamin K seems to have an antiapoptotic and anti-inflammatory effect mediated by the activation of Growth Arrest Specific Gene 6 and Protein S. Moreover, this vitamin is involved in sphingolipids metabolism, a class of lipids that participate in the proliferation, differentiation, and survival of brain cells. An altered expression in sphingolipids profile has been related to neuroinflammation and neurodegeneration. This review stems from a growing interest in the role of vitamin K in brain functions, especially in cognition, also in view of an expected increase of prevalence of Alzheimer's disease and other forms of dementia. It collects recent researches that show interesting, even though not definitive, evidence of a direct correlation between vitamin K levels and cognitive performance. Moreover, vitamin K antagonists, used worldwide as oral anticoagulants, according to recent studies may have a negative influence on cognitive domains such as visual memory, verbal fluency and brain volume. The aim of this review is to analyze the evidence of clinical studies carried out up to date on the relationship between vitamin K intake and cognitive performances. The involvement of vitamin K antagonists (VKAs) in declining cognitive performances is also addressed separately

I papiri matematici del Medio Regno

A form of thought in the pure state stripped of the garb of words, mathematics embodies in an essential manner, with numbers and operations, the logical structures of those who have created it. Hence it can represent a source of insight into a lost civilisation. This study has essentially two objectives: to sketch out a compendium of the mathematical themes and techniques known in the Egypt of the Middle Kingdom, and to deduce from these as much information as possible on the Egyptian mentality. The mathematical evidence is tackled here from a dual viewpoint: as the tools of an empirical science of calculation, and also as emblematic of a mode of conceiving mathematics as an instrument of knowledge in the sense of being a reflection of the established order. The evidence throws up the fact that mathematics is not conceived as an abstract science, but rather as the practical preliminary tool of a physics understood as measurement of the quantities and the greatness of the visible world. The role which it plays in the cognitive process is not independent, but always connected with questions of a philosophical nature. It is therefore a practical science in the sense in which the Egyptians understood it, that is an instrument for understanding nature: a science at the service of theology