The investigation of the physiological and pathological processes involved in fear perception is complicated due to the difficulties in reliably eliciting and measuring the complex construct of fear. This study proposes a novel approach to induce and measure subjective fear and its physiological correlates combining virtual reality (VR) with a mixed-effects model based on skin conductance (SC). Specifically, we developed a new VR scenario applying specific guidelines derived from horror movies and video games. Such a VR environment was used to induce fear in eighteen volunteers in an experimental protocol, including two relaxation scenarios and a neutral virtual environment. The SC signal was acquired throughout the experiment, and after each virtual scenario, the emotional state and fear perception level were assessed using psychometric scales. We statistically evaluated the greatest sympathetic activation induced by the fearful scenario compared to the others, showing significant results for most SC-derived features. Finally, we developed a rigorous mixed-effects model to explain the perceived fear as a function of the SC features. Model-fitting results showed a significant relationship between the fear perception scores and a combination of features extracted from both fast- and slow-varying SC components, proposing a novel solution for a more objective fear assessment.

Anxiety symptoms are important contributors to the global health-related burden. Low-intensity interventions have been proposed to reduce anxiety symptoms in the population. Among these, biofeedback (BF) offers an effective approach to reducing anxiety. In the present study, BF was integrated into a novel virtual reality (VR) architecture to enhance BF's effectiveness to i) evaluate the feasibility of a VR-based single-session BF in teaching participants to self-regulate; ii) compare the BF aiming at reducing sympathetic (measured though the tonic level of skin conductance, SCL) versus increasing cardiac vagal (i.e., normalized high frequency of heart rate variability, HFnu-HRV) activation, and iii) evaluate which of the two VR-BF single-sessions was most effective in reducing perceived state anxiety. 20 healthy participants underwent both SCL- and HFnu-based in a single session VR-BF. Results showed the feasibility of a short single-session VR-BF and the effectiveness of both VR-BF sessions in reducing perceived state anxiety. Moreover, SCL-based VR-BF determined a significant reduction in sympathetic activation and in sympathovagal balance as well as a greater reduction in perceived state anxiety compared to HFnu-based VR-BF. SCL-based VR-BF represents a safe and effective intervention in reducing anxiety while enhancing adaptive psychophysiological activation.

Alzheimer’s disease (AD) is the leading cause of dementia, but the pathogenetic factors are not yet well known, and the relationships between brain and systemic biochemical derangements and disease onset and progression are unclear. We aim to focus on blood biomarkers for an accurate prognosis of the disease. We used a dataset characterized by longitudinal findings collected over the past 10 years from 90 AD patients. The dataset included 277 observations (both clinical and biochemical ones, encompassing blood analytes encompassing routine profiles for different organs, together with immunoinflammatory and oxidative markers). Subjects were grouped into four severity classes according to the Clinical Dementia Rating (CDR) Scale: mild (CDR = 0.5 and CDR = 1), moderate (CDR = 2), severe (CDR = 3) and very severe (CDR = 4 and CDR = 5). Statistical models were used for the identification of potential blood markers of AD progression. Moreover, we employed the Pathfinder tool of the Reactome database to investigate the biological pathways in which the analytes of interest could be involved. Statistical results reveal an inverse significant relation between four analytes (high-density cholesterol, total cholesterol, iron and ferritin) with AD severity. In addition, the Reactome database suggests that such analytes could be involved in pathways that are altered in AD progression. Indeed, the identified blood markers include molecules that reflect the heterogeneous pathogenetic mechanisms of AD. The combination of such blood analytes might be an early indicator of AD progression and constitute useful therapeutic targets.

The investigation of the physiological and pathological processes involved in fear perception is complicated due to the difficulties in reliably eliciting and measuring the complex construct of fear. This study proposes a novel approach to induce and measure subjective fear and its physiological correlates combining virtual reality (VR) with a mixed-effects model based on skin conductance (SC). Specifically, we developed a new VR scenario applying specific guidelines derived from horror movies and video games. Such a VR environment was used to induce fear in eighteen volunteers in an experimental protocol, including two relaxation scenarios and a neutral virtual environment. The SC signal was acquired throughout the experiment, and after each virtual scenario, the emotional state and fear perception level were assessed using psychometric scales. We statistically evaluated the greatest sympathetic activation induced by the fearful scenario compared to the others, showing significant results for most SC-derived features. Finally, we developed a rigorous mixed-effects model to explain the perceived fear as a function of the SC features. Model-fitting results showed a significant relationship between the fear perception scores and a combination of features extracted from both fast- and slow-varying SC components, proposing a novel solution for a more objective fear assessment.