Backtranslation of EEG biomarkers of Alzheimer's disease from patients to mouse model

The present Ph.D. thesis has been mainly developed on the data of the project with the short name PharmaCog (2010-2015), granted by the European Framework Programme 7 with about 28 millions of Euro (i.e. Innovative Medicine Initiative, IMI, grant agreement n°115009; www.pharmacog.org). This project involved 15 academic institutions, 12 global pharmaceutical companies, and 5 small and medium sized enterprises (SMEs). The PharmaCog project aimed at improving the pathway of drug discovery in Alzheimer’s disease (AD), based on a major interest of pharma companies, namely the validation of electrophysiological, neuroimaging, and blood biomarkers possibly sensitive to the effect of disease-modifying drugs reducing Ab42 in the brain in AD patients at the prodromal stage of amnesic mild cognitive impairment (aMCI). The core concept of the PharmaCog project was that the pathway of drug discovery in AD may be enhanced by (1) the validation of biomarkers derived from blood, EEG, magnetic resonance imaging (MRI), and positron emission tomography (PET) in patients with aMCI due to AD diagnosed by in-vivo measurement of Ab42 and phospho-tau in the brain and (2) the evaluation of the translational value of those human biomarkers in wild type (WT) mice and animal models of AD including transgenic mice with the mutation of PS1 and/or APP (i.e. PDAPP and TASTPM strains). Those genetic factors induce an abnormal accumulation of Ab42 in the brain and related cognitive deficits. The expected results may be (1) the identification of a matrix of biomarkers sensitive to the prodromal AD (aMCI cognitive status) and its progression in patients and (2) the selection of similar biomarkers related to AD neuropathology and cognitive deficits in PDAPP and TASTPM strains. These biomarkers were expected to be very useful in clinical trials testing the efficacy and neurobiological impact of new disease-modifying drugs against prodromal AD. For the development of this Ph.D. thesis, the access to the experiments and the data of the PharmaCog project was allowed by Prof. Claudio Babiloni, leader of an Italian Unit (University of Foggia in 2010-2012 and Sapienza University of Rome in 2013-2015) of the PharmaCog Consortium and coordinator of study activities relative to biomarkers derived from electroencephalographic (EEG) signals recorded from human subjects and animals in that project. Specifically, Prof. Claudio Babiloni was in charge for the centralized qualification and analysis of EEG data recorded from aMCI patients (Work Package 5, WP5) and transgenic mouse models of AD such as PDAPP and TASTPM strains (WP6). The data of the present Ph.D. thesis mostly derived from the WP5 and WP6. This document illustrating the Ph.D. thesis is structured in three main Sections: ▪ An Introductive part illustrating concisely the AD neuropathology, the mouse models of AD used in this thesis, and basic concepts of EEG techniques useful to understand the present study results; ▪ An Experimental part describing the result of the four research studies led in the framework of this Ph.D. project. Two of these studies were published in international journals registered in ISI/PubMed with impact factor, while the other two are being currently under minor revisions in those journals; ▪ A Conclusion section

Role of Unrealistic Optimism in College Student Alcohol-Related Risky Sexual Behavior

Introduction: Risky sexual behavior (RSB), especially after alcohol use (RSB-A), remains an issue among college students (Cooper, 2002). Engaging in RSB often results in sexually transmitted infections and unintended pregnancy, which are increasing at alarming rates among young adults (CDC, 2016; Finer & Zolna, 2014). One risk factor for engaging in RSB and RSB-A may be unrealistic optimism (UO), or a misperception of risk of experiencing a negative event. Though UO has been found to be related to engagement in certain behaviors such as smoking (Shepperd et al., 2013), less is known about the role of UO in RSB-A among college students. The purpose of the current study was to investigate the presence of UO in a college student sample, analyze associations between UO and current RSB and RSB-A patterns, and to analyze alcohol use as a moderator in the relation between RSB and RSB-related UO.Methods: Undergraduate students (N = 665) from a large, Southern Plains university completed an online study assessing RSB patterns, alcohol use, and risk perceptions of RSB-related consequences.Results: Dependent sample t-tests revealed that, relative to perceived risk of the average college student, students reported lower perceived personal risk of sexual activity (with and without concurrent alcohol use), unintended pregnancy, and contracting HPV and chlamydia (ps < .01). One-sample t-tests revealed that, compared to national data, students overestimated their own chances of sexual engagement with 1-3 partners and underestimated chances of HPV infection and sexual engagement with 4 or more partners in the next year (ps < .01). Alcohol use was found as a moderator between RSB and sexual activity with one partner, condom use, sexual activity after alcohol use, and condom use during alcohol-related sexual activity (ps < .001) such that lower alcohol use strengthened these relationships.Discussion: The current study demonstrated the presence of UO regarding RSB-A and related consequences in a college student sample, but also demonstrated acknowledgement of higher risk of these consequences among those reporting higher alcohol use. Future research should investigate these behaviors and consequences over time. Implications for intervention are discussed.Psycholog

Social norms of alcohol use among American Indian college students

American Indian (AI) peoples are at higher risk for alcohol use disorder and related health consequences compared to the general population. Descriptive and injunctive norms have been found to be a significant risk factor for high-risk drinking, especially among college students. However, this research has rarely been extended to the AI college student population. The current study aimed to analyze descriptive and injunctive reference groups, or groups from which to draw normative information. The current study further investigated ethnic identity, or strength of one’s ties to their AI culture, as a moderator between norms and actual drinking patterns. Undergraduate AI students (N = 356) from a Southern Plains university completed an online survey assessing drinking patterns, descriptive norms (best male/female friend, typical male/female college student, typical AI male/female college student), injunctive norms (typical male/female college student, typical AI male/female college student), and ethnic identity. Repeated ANOVAs revealed that, compared to actual drinking levels, students overestimated all descriptive norm reference groups except for best female friend. Compared to actual injunctive norms, students further overestimated all injunctive norm groups except for AI female norms. Notably, students estimated lower drinking levels for AI-specific groups than typical student groups. Negative binomial regressions revealed descriptive AI male and best male friend reference groups significantly predicted actual drinking patterns for men, while only best female friend norms predicted actual drinking patterns for women. Lastly, ethnic identity was unrelated to drinking and did not serve as a significant moderator between norms and drinking. Findings may be used to inform brief norms-based interventions, as AI-specific reference groups may have a bigger impact on reducing drinking among men, but not women. Further research on the role of ethnic identity on drinking is warranted. Results suggest the use of different reference groups for AI men and women in brief, norms-based alcohol interventions

On-going frontal alpha rhythms are dominant in passive state and desynchronize in active state in adult gray mouse lemurs

The gray mouse lemur (Microcebus murinus) is considered a useful primate model for translational research. In the framework of IMI PharmaCog project (Grant Agreement n°115009, www.pharmacog.org), we tested the hypothesis that spectral electroencephalographic (EEG) markers of motor and locomotor activity in gray mouse lemurs reflect typical movement-related desynchronization of alpha rhythms (about 8-12 Hz) in humans. To this aim, EEG (bipolar electrodes in frontal cortex) and electromyographic (EMG; bipolar electrodes sutured in neck muscles) data were recorded in 13 male adult (about 3 years) lemurs. Artifact-free EEG segments during active state (gross movements, exploratory movements or locomotor activity) and awake passive state (no sleep) were selected on the basis of instrumental measures of animal behavior, and were used as an input for EEG power density analysis. Results showed a clear peak of EEG power density at alpha range (7-9 Hz) during passive state. During active state, there was a reduction in alpha power density (8-12 Hz) and an increase of power density at slow frequencies (1-4 Hz). Relative EMG activity was related to EEG power density at 2-4 Hz (positive correlation) and at 8-12 Hz (negative correlation). These results suggest for the first time that the primate gray mouse lemurs and humans may share basic neurophysiologic mechanisms of synchronization of frontal alpha rhythms in awake passive state and their desynchronization during motor and locomotor activity. These EEG markers may be an ideal experimental model for translational basic (motor science) and applied (pharmacological and non-pharmacological interventions) research in Neurophysiology

Relationship between default mode network and resting-state electroencephalographic alpha rhythms in cognitively unimpaired seniors and patients with dementia due to alzheimer’s disease

Here we tested the hypothesis of a relationship between the cortical default mode network (DMN) structural integrity and the resting-state electroencephalographic (rsEEG) rhythms in patients with Alzheimer’s disease with dementia (ADD). Clinical and instrumental datasets in 45 ADD patients and 40 normal elderly (Nold) persons originated from the PDWAVES Consortium (www.pdwaves.eu). Individual rsEEG delta, theta, alpha, and fixed beta and gamma bands were considered. Freeware platforms served to derive (1) the (gray matter) volume of the DMN, dorsal attention (DAN), and sensorimotor (SMN) cortical networks and (2) the rsEEG cortical eLORETA source activities. We found a significant positive association between the DMN gray matter volume, the rsEEG alpha source activity estimated in the posterior DMN nodes (parietal and posterior cingulate cortex), and the global cognitive status in the Nold and ADD participants. Compared with the Nold, the ADD group showed lower DMN gray matter, lower rsEEG alpha source activity in those nodes, and lower global cognitive status. This effect was not observed in the DAN and SMN. These results suggest that the DMN structural integrity and the rsEEG alpha source activities in the DMN posterior hubs may be related and predict the global cognitive status in ADD and Nold persons.IRCCS San Raffaele Pisana of Rome ; Ministero della Salut

Mirror visual feedback during unilateral finger movements is related to the desynchronization of cortical electroencephalographic somatomotor alpha rhythms

Using a mirror adequately oriented, the motion of just one hand induces the illusion of the movement with the other hand. Here, we tested the hypothesis that such a mirror phenomenon may be underpinned by an electroencephalographic (EEG) event‐related desynchronization/synchronization (ERD/ERS) of central alpha rhythms (around 10 Hz) as a neurophysiological measure of the interactions among cerebral cortex, basal ganglia, and thalamus during movement preparation and execution. Eighteen healthy right‐handed male participants performed standard auditory‐triggered unilateral (right) or bilateral finger movements in the No Mirror (M−) conditions. In the Mirror (M+) condition, the unilateral right finger movements were performed in front of a mirror oriented to induce the illusion of simultaneous left finger movements. EEG activity was recorded from 64 scalp electrodes, and the artifact‐free event‐related EEG epochs were used to compute alpha ERD. In the M− conditions, a bilateral prominent central alpha ERD was observed during the bilateral movements, while left central alpha ERD and right alpha ERS were seen during unilateral right movements. In contrast, the M+ condition showed significant bilateral and widespread alpha ERD during the unilateral right movements. These results suggest that the above illusion of the left movements may be related to alpha ERD measures reflecting excitatory desynchronizing signals in right lateral premotor and primary somatomotor areas possibly in relation to basal ganglia‐thalamic loops

La comunicació cap a l'usuari al Campus del Baix Llobregat

La Biblioteca del Campus del Baix Llobregat de la Universitat Politècnica de Catalunya a Castelldefels dona suport a les dues escoles del Campus: l’Escola Superior d’Agricultura de Barcelona (ESAB), l’Escola d’Enginyeria de Telecomunicació i Aeroespacial de Castelldefels (EETAC) i a la comunitat present al Campus. Actualment existeixen diferents canals de comunicació. Un dels objectius prioritaris d’aquesta comunicació és donar a conèixer com funciona el servei de comunicació de la biblioteca i del campus del Baix Llobregat i quina ha estat l’evolució i modificació dels canals. S’han realitzat diferents tècniques d’avaluació (Design Thinking, enquestes...) dels nostres canals, per saber les opinions i el feedback dels nostres usuaris i arran d’aquestes opinions hem descobert i aplicat canvis en els sistemes de comunicació.The Campus of Baix Llobregat Library located in Castelldefles gives services to two UPC schools: EETAC(Castelldefels School of Telecommunications and Aerospace Engineering) and ESAB (Barcelona School of Agricultural Engineering) and the rest of community who study or work in the campus. In the Campus of Baix Llobregat there are several communication channels. The main purpose of this article is to show the evolution of the channels from the beginning of the campus (ten years ago) to our days. This evolution is promoted by the change on the users needs and for the new channels appeared. The information to change a channel or communication systems comes from the user’s interview and from the library experience.Postprint (author's final draft

Liver Biomarkers and Lipid Profiles in Mexican and Mexican-American 10- to 14-Year-Old Adolescents at Risk for Type 2 Diabetes

Proyecto de investigación que describe la presencia de diversos factores de riesgo para desarrollar diabetes mellitus tipo 2 en adolescentes.Liver enzymes alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) are markers for type 2 diabetes mellitus (T2DM); alkaline phosphatase is a marker of liver disease. Mexican-American adolescents are disproportionately affected by T2DM, while in Mexico its prevalence is emerging. We assessed liver biomarkers and lipid profiles among Mexican and Mexican-American adolescents 10–14 years old with high/low risk of T2DM through a cross-sectional, descriptive study (Texas n = 144; Mexico n = 149). We included family medical histories, anthropometry, and blood pressure. Obesity was present in one-third of subjects in both sites. ALT (UL) was higher (p < 0 001) in high-risk adolescents (23.5 ± 19.5 versus 17.2 ± 13.4 for males, 19.7 ± 11.6 versus 15.1 ± 5.5 for females), in Toluca and in Texas (26.0 ± 14.7 versus 20.0 ± 13.2 for males, 18.2 ± 13.4 versus 14.6 ± 10.1 for females), as well as GGT (UL) (p < 0 001) (18.7 ± 11.1 versus 12.4 ± 2.3 for males, 13.6 ± 5.8 versus 11.5 ± 3.9 for Mexican females; 21.0 ± 6.8 versus 15.4 ± 5.5 for males, 14.3 ± 5.0 versus 13.8 ± 5.3 for females in Texas). We found no differences by sex or BMI. Total cholesterol and HDL were higher among Mexican-Americans (p < 0 001). In conclusion, multiple risk factors were present in the sample. We found differences by gender and between high and low risk for T2DM adolescents in all liver enzymes in both sites.Fondo Semilla UAEM-UNTHS

Patients with Alzheimer's disease dementia show partially preserved parietal 'hubs' modeled from resting-state alpha electroencephalographic rhythms

IntroductionGraph theory models a network by its nodes (the fundamental unit by which graphs are formed) and connections. 'Degree' hubs reflect node centrality (the connection rate), while 'connector' hubs are those linked to several clusters of nodes (mainly long-range connections). MethodsHere, we compared hubs modeled from measures of interdependencies of between-electrode resting-state eyes-closed electroencephalography (rsEEG) rhythms in normal elderly (Nold) and Alzheimer's disease dementia (ADD) participants. At least 5 min of rsEEG was recorded and analyzed. As ADD is considered a 'network disease' and is typically associated with abnormal rsEEG delta (<4 Hz) and alpha rhythms (8-12 Hz) over associative posterior areas, we tested the hypothesis of abnormal posterior hubs from measures of interdependencies of rsEEG rhythms from delta to gamma bands (2-40 Hz) using eLORETA bivariate and multivariate-directional techniques in ADD participants versus Nold participants. Three different definitions of 'connector' hub were used. ResultsConvergent results showed that in both the Nold and ADD groups there were significant parietal 'degree' and 'connector' hubs derived from alpha rhythms. These hubs had a prominent outward 'directionality' in the two groups, but that 'directionality' was lower in ADD participants than in Nold participants. DiscussionIn conclusion, independent methodologies and hub definitions suggest that ADD patients may be characterized by low outward 'directionality' of partially preserved parietal 'degree' and 'connector' hubs derived from rsEEG alpha rhythms