Detecting cognitive states from the analysis of structural and functional images of the brain: two applications of Multi-Voxel Pattern Analysis on MRI and fMRI data

In recent years, the efficacy and accuracy of multivariate analysis techniques on neuroimaging data has been tested on different topics. These methods have shown the ability to decode mental states from the analysis of brain scans, for this reason it has been called “brain reading”. The predictions can be applied to general mental states, referring to stable conditions not related to a contingent task (e.g., a neurological diagnosis), or specific mental states, referring to task-related cognitive processes (e.g., the perception of a category of stimuli). According to several neuroscientists, brain reading approach can potentially be useful for applications in both clinical and forensic neuroscience in the future. In the present dissertation, two applications of the brain reading approach are presented on two relevant topics for clinical and forensic neuroscience that have not been extensively investigated with these methods. In Section A, this approach is tested on decoding different levels of Cognitive Reserve from the pattern of grey matter volume, in two MRI studies. In Section B two fMRI studies investigate the possibility of decoding real autobiographical memories from brain activity. The aim of this thesis is to contribute to the amount of studies showing the usefulness of multivariate techniques in decoding “mental states” starting from the analysis of structural and functional brain imaging data, as well as the potential uses in clinical and forensic settings

Me, myself and you: How self-consciousness influences time perception

Several investigations have shown that the processing of self-relevant information differs from processing objective information. The present study aimed to investigate the effect of social stimuli on subjective time processing. Here, social stimuli are images of an unknown male and female person and an image of participants' self. Forty university students were tested with a time reproduction task in which they were asked to reproduce the duration of the stimulus previously presented. Images of others or themselves were used to mark the temporal intervals. Participants also performed questionnaires to evaluate the level of anxiety and depression as well as self-consciousness. A generalised linear mixed-effects model approach was adopted. Results showed that male participants with higher Private Self-Consciousness scores showed higher time perception accuracy than females. Also, female participants reported higher scores for the Public Self-Consciousness subscale than male participants. The findings are discussed in terms of social context models of how attention is solicited and arousal is generated by social stimuli, highlighting the effect of social context on subjective perception of time

Extra-telomeric functions of telomerase in the pathogenesis of Epstein-Barr virus-driven B-cell malignancies and potential therapeutic implications

Abstract The Epstein-Barr virus (EBV) is a ubiquitous human \u3b3-herpesvirus causally linked to a broad spectrum of both lymphoid and epithelial malignancies. In order to maintain its persistence in host cells and promote tumorigenesis, EBV must restrict its lytic cycle, which would ultimately lead to cell death, selectively express latent viral proteins, and establish an unlimited proliferative potential. The latter step depends on the maintenance of telomere length provided by telomerase. The viral oncoprotein LMP-1 activates TERT, the catalytic component of telomerase. In addition to its canonical role in stabilizing telomeres, TERT may promote EBV-driven tumorigenesis through extra-telomeric functions. TERT contributes toward preserving EBV latency; in fact, through the NOTCH2/BATF pathway, TERT negatively affects the expression of BZLF1, the master regulator of the EBV lytic cycle. In contrast, TERT inhibition triggers a complete EBV lytic cycle, leading to the death of EBV-infected cells. Interestingly, short-term TERT inhibition causes cell cycle arrest and apoptosis, partly by inducing telomere-independent activation of the ATM/ATR/TP53 pathway. Importantly, TERT inhibition also sensitizes EBV-positive tumor cells to antiviral therapy and enhances the pro-apoptotic effects of chemotherapeutic agents. We provide here an overview on how the extra-telomeric functions of TERT contribute to EBV-driven tumorigenesis. We also discuss the potential therapeutic approach of TERT inhibition in EBV-driven malignancies

Short-term inhibition of TERT induces telomere length-independent cell cycle arrest and apoptotic response in EBV-immortalized and transformed B cells

open7siBesides its canonical role in stabilizing telomeres, telomerase reverse transcriptase (TERT) may promote tumorigenesis through extra-telomeric functions. The possible therapeutic effects of BIBR1532 (BIBR), a powerful TERT inhibitor, have been evaluated in different cellular backgrounds, but no data are currently available regarding Epstein-Barr virus (EBV)-driven B-cell malignancies. Our aim was to characterize the biological effects of TERT inhibition by BIBR on EBV-immortalized lymphoblastoid cell lines (LCLs) and fully transformed Burkitt's lymphoma (BL) cell lines. We found that BIBR selectively inhibits telomerase activity in TERT-positive 4134/Late and 4134/TERT+ LCLs and EBV-negative BL41 and EBV-positive BL41/B95.8 BL cell lines. TERT inhibition led to decreased cell proliferation, accumulation of cells in the S-phase and ultimately to increased apoptosis, compared with mock-treated control cells. All these effects occurred within 72 h and were not observed in BIBR-treated TERT-negative 4134/TERT- and U2OS cells. The cell cycle arrest and apoptosis, consequent upon short-term TERT inhibition, were associated with and likely dependent on the activation of the DNA damage response (DDR), highlighted by the increased levels of γH2AX and activation of ATM and ATR pathways. Analyses of the mean and range of telomere lengths and telomere dysfunction-induced foci indicated that DDR after short-term TERT inhibition was not related to telomere dysfunction, thus suggesting that TERT, besides stabilizing telomere, may protect DNA via telomere-independent mechanisms. Notably, TERT-positive LCLs treated with BIBR in combination with fludarabine or cyclophosphamide showed a significant increase in the number of apoptotic cells with respect to those treated with chemotherapeutic agents alone. In conclusion, TERT inhibition impairs cell cycle progression and enhances the pro-apoptotic effects of chemotherapeutic agents in TERT-positive cells. These results support new therapeutic applications of TERT inhibitors in EBV-driven B-cell malignancies.openCeleghin, Andrea; Giunco, Silvia; Freguja, Riccardo; Zangrossi, Manuela; Nalio, Silvia; Dolcetti, Riccardo; De Rossi, AnitaCeleghin, Andrea; Giunco, Silvia; Freguja, Riccardo; Zangrossi, Manuela; Nalio, Silvia; Dolcetti, Riccardo; DE ROSSI, Anit

Cognitive reserve in dementia: Implications for cognitive training

open9noCognitive reserve (CR) is a potential mechanism to cope with brain damage. The aim of this study was to evaluate the effect of CR on a cognitive training (CT) in a group of patients with dementia. Eighty six participants with mild to moderate dementia were identified by their level of CR quantified by the CR Index questionnaire (CRIq) and underwent a cycle of CT. A global measure of cognition mini mental state examination (MMSE) was obtained before (T0) and after (T1) the training. Multiple linear regression analyses highlighted CR as a significant factor able to predict changes in cognitive performance after the CT. In particular, patients with lower CR benefited from a CT program more than those with high CR. These data show that CR can modulate the outcome of a CT program and that it should be considered as a predictive factor of neuropsychological rehabilitation training efficacy in people with dementia.openMondini, Sara; Madella, Ileana; Zangrossi, Andrea; Bigolin, Angela; Tomasi, Claudia; Michieletto, Marta; Villani, Daniele; Di Giovanni, Giuseppina; Mapelli, DanielaMondini, Sara; Madella, Ileana; Zangrossi, Andrea; Bigolin, Angela; Tomasi, Claudia; Michieletto, Marta; Villani, Daniele; Di Giovanni, Giuseppina; Mapelli, Daniel

Detecting cognitive states from the analysis of structural and functional images of the brain: two applications of Multi-Voxel Pattern Analysis on MRI and fMRI data

In recent years, the efficacy and accuracy of multivariate analysis techniques on neuroimaging data has been tested on different topics. These methods have shown the ability to decode mental states from the analysis of brain scans, for this reason it has been called “brain reading”. The predictions can be applied to general mental states, referring to stable conditions not related to a contingent task (e.g., a neurological diagnosis), or specific mental states, referring to task-related cognitive processes (e.g., the perception of a category of stimuli). According to several neuroscientists, brain reading approach can potentially be useful for applications in both clinical and forensic neuroscience in the future. In the present dissertation, two applications of the brain reading approach are presented on two relevant topics for clinical and forensic neuroscience that have not been extensively investigated with these methods. In Section A, this approach is tested on decoding different levels of Cognitive Reserve from the pattern of grey matter volume, in two MRI studies. In Section B two fMRI studies investigate the possibility of decoding real autobiographical memories from brain activity. The aim of this thesis is to contribute to the amount of studies showing the usefulness of multivariate techniques in decoding “mental states” starting from the analysis of structural and functional brain imaging data, as well as the potential uses in clinical and forensic settings.Negli ultimi anni, l’efficacia e l’accuratezza di tecniche di analisi multivariata di analisi dei dati di neuroimmagine sono state testate su diversi argomenti. Questi metodi hanno mostrato la possibilità di decodificare stati mentali a partire dall’analisi di dati di neuroimmagine cerebrale, per questo motivo sono stati indicati con l’espressione “brain reading”. Le inferenze possono essere applicate a “stati mentali” generali, ovvero condizioni stabili e non legate ad uno specifico task (ad esempio una diagnosi neurologica), o a specifici “stati mentali”, ovvero processi cognitivi elicitati da specifici task (ad esempio la percezione di stimoli di una data categoria). Secondo molti autori le caratteristiche di questo approccio lo rendono strumento potenzialmente utile per future applicazioni sia cliniche che forensi. Nel presente lavoro sono state testate due applicazioni dell’approccio di brain reading su temi rilevanti per le neuroscienze in ambito clinico e forense, e poco studiati con questi metodi. Nella Sezione A verranno presentati due studi su dati MRI sulla possibilità di discriminare tra diversi livelli di Riserva Cognitiva a partire dal pattern di volume di materia grigia cerebrale. Nella Sezione B in due studi fMRI abbiamo investigato la possibilità di rilevare ricordi autobiografici sulla base dell’attività cerebrale. L’obiettivo del presente lavoro è quello di contribuire al crescente numero di studi che hanno discusso l’utilità di tecniche multivariate nella decodifica di “stati mentali” a partire dall’analisi di dati di neuroimmagine strutturale o funzionale, e le potenziali applicazioni applicazioni chiniche e forensi

Autobiographical Implicit Association test (aIAT) and eye movements: fixations topography enables detection of autobiographical memories

Autobiographical memory is the capacity to recollect memories of personally experienced events. The detection of such memories plays a key role in criminal trials. Among behavioral memory-detection methods, the autobiographical Implicit Association Test (aIAT) has gained popularity for its flexibility and suitability for forensic applications. The aIAT is a reaction time-based methodology aiming to assess whether information about an event is encoded in the respondent’s mind. In this study we introduced the eye-D index, a measure based on the topography of fixations while performing the aIAT, as an additional measure to detect autobiographical memories in a covert manner. In this study, participants were involved in a mock-crime experiment in which they could act as Guilty or Innocent. One week later all participants underwent the aIAT to investigate the presence of the crime-related memory. Guilty participants showed a higher number of fixations towards the category labels in the block in which true sentences shared the same response key with crime-related sentences, as compared to the block in which true sentences were paired with sentences describing an alternative version. Innocent participants showed the opposite pattern. This unbalanced allocation of attention to the category labels was quantified by the eye-D index and was found to be highly correlated to the standard aIAT-D index. This suggests that more fixations to the category labels could indicate increased cognitive load and monitoring of response conflicts. These preliminary results highlight eye-tracking as a tool to detect autobiographical memories covertly while performing the aIAT

VisualExploration_1

This project is related to the paper entitled "Visual exploration dynamics are low-dimensional and driven by intrinsic factors" by Andrea Zangrossi and colleagues (2021, Comms. Bio