A Common Protocol for Agent-Based Social Simulation

Traditional (i.e. analytical) modelling practices in the social sciences rely on a very well established, although implicit, methodological protocol, both with respect to the way models are presented and to the kinds of analysis that are performed. Unfortunately, computer-simulated models often lack such a reference to an accepted methodological standard. This is one of the main reasons for the scepticism among mainstream social scientists that results in low acceptance of papers with agent-based methodology in the top journals. We identify some methodological pitfalls that, according to us, are common in papers employing agent-based simulations, and propose appropriate solutions. We discuss each issue with reference to a general characterization of dynamic micro models, which encompasses both analytical and simulation models. In the way, we also clarify some confusing terminology. We then propose a three-stage process that could lead to the establishment of methodological standards in social and economic simulations.Agent-Based, Simulations, Methodology, Calibration, Validation, Sensitivity Analysis

A Common Protocol for Agent-Based Social Simulation

Traditional (i.e. analytical) modelling practices in the social sciences rely on a very well established, although implicit, methodological protocol, both with respect to the way models are presented and to the kinds of analysis that are performed. Unfortunately, computer-simulated models often lack such a reference to an accepted methodological standard. This is one of the main reasons for the scepticism among mainstream social scientists that results in low acceptance of papers with agent-based methodology in the top journals. We identify some methodological pitfalls that, according to us, are common in papers employing agent-based simulations, and propose appropriate solutions. We discuss each issue with reference to a general characterization of dynamic micro models, which encompasses both analytical and simulation models. In the way, we also clarify some confusing terminology. We then propose a three-stage process that could lead to the establishment of methodological standards in social and economic simulations.Agent-based, simulations, methodology, calibration, validation.

Systemic and central nervous system neuroinflammatory signatures of neuropsychiatric symptoms and related cognitive decline in older people.

Neuroinflammation may contribute to psychiatric symptoms in older people, in particular in the context of Alzheimer's disease (AD). We sought to identify systemic and central nervous system (CNS) inflammatory alterations associated with neuropsychiatric symptoms (NPS); and to investigate their relationships with AD pathology and clinical disease progression. We quantified a panel of 38 neuroinflammation and vascular injury markers in paired serum and cerebrospinal fluid (CSF) samples in a cohort of cognitively normal and impaired older subjects. We performed neuropsychiatric and cognitive evaluations and measured CSF biomarkers of AD pathology. Multivariate analysis determined serum and CSF neuroinflammatory alterations associated with NPS, considering cognitive status, AD pathology, and cognitive decline at follow-up visits. NPS were associated with distinct inflammatory profiles in serum, involving eotaxin-3, interleukin (IL)-6 and C-reactive protein (CRP); and in CSF, including soluble intracellular cell adhesion molecule-1 (sICAM-1), IL-8, 10-kDa interferon-γ-induced protein, and CRP. AD pathology interacted with CSF sICAM-1 in association with NPS. Presenting NPS was associated with subsequent cognitive decline which was mediated by CSF sICAM-1. Distinct systemic and CNS inflammatory processes are involved in the pathophysiology of NPS in older people. Neuroinflammation may explain the link between NPS and more rapid clinical disease progression

Cerebrospinal Fluid Cortisol and Dehydroepiandrosterone Sulfate, Alzheimer's Disease Pathology, and Cognitive Decline.

Elevated cortisol levels have been reported in Alzheimer's disease (AD) and may accelerate the development of brain pathology and cognitive decline. Dehydroepiandrosterone sulfate (DHEAS) has anti-glucocorticoid effects and it may be involved in the AD pathophysiology. To investigate associations of cerebrospinal fluid (CSF) cortisol and DHEAS levels with (1) cognitive performance at baseline; (2) CSF biomarkers of amyloid pathology (as assessed by CSF Aβ levels), neuronal injury (as assessed by CSF tau), and tau hyperphosphorylation (as assessed by CSF p-tau); (3) regional brain volumes; and (4) clinical disease progression. Individuals between 49 and 88 years (n = 145) with mild cognitive impairment or dementia or with normal cognition were included. Clinical scores, AD biomarkers, brain MRI volumetry along with CSF cortisol and DHEAS were obtained at baseline. Cognitive and functional performance was re-assessed at 18 and 36 months from baseline. We also assessed the following covariates: apolipoprotein E (APOE) genotype, BMI, and education. We used linear regression and mixed models to address associations of interest. Higher CSF cortisol was associated with poorer global cognitive performance and higher disease severity at baseline. Cortisol and cortisol/DHEAS ratio were positively associated with tau and p-tau CSF levels, and negatively associated with the amygdala and insula volumes at baseline. Higher CSF cortisol predicted more pronounced cognitive decline and clinical disease progression over 36 months. Higher CSF DHEAS predicted more pronounced disease progression over 36 months. Increased cortisol in the CNS is associated with tau pathology and neurodegeneration, and with decreased insula and amygdala volume. Both CSF cortisol and DHEAS levels predict faster clinical disease progression. These results have implications for the identification of patients at risk of rapid decline as well as for the development of interventions targeting both neurodegeneration and clinical manifestations of AD

Periinfarct rewiring supports recovery after primary motor cortex stroke.

After stroke restricted to the primary motor cortex (M1), it is uncertain whether network reorganization associated with recovery involves the periinfarct or more remote regions. We studied 16 patients with focal M1 stroke and hand paresis. Motor function and resting-state MRI functional connectivity (FC) were assessed at three time points: acute (<10 days), early subacute (3 weeks), and late subacute (3 months). FC correlates of recovery were investigated at three spatial scales, (i) ipsilesional non-infarcted M1, (ii) core motor network (M1, premotor cortex (PMC), supplementary motor area (SMA), and primary somatosensory cortex), and (iii) extended motor network including all regions structurally connected to the upper limb representation of M1. Hand dexterity was impaired only in the acute phase (P = 0.036). At a small spatial scale, clinical recovery was more frequently associated with connections involving ipsilesional non-infarcted M1 (Odds Ratio = 6.29; P = 0.036). At a larger scale, recovery correlated with increased FC strength in the core network compared to the extended motor network (rho = 0.71;P = 0.006). These results suggest that FC changes associated with motor improvement involve the perilesional M1 and do not extend beyond the core motor network. Core motor regions, and more specifically ipsilesional non-infarcted M1, could hence become primary targets for restorative therapies

Plasma neurofilament light and phosphorylated tau 181 as biomarkers of Alzheimer's disease pathology and clinical disease progression.

To assess the performance of plasma neurofilament light (NfL) and phosphorylated tau 181 (p-tau181) to inform about cerebral Alzheimer's disease (AD) pathology and predict clinical progression in a memory clinic setting. Plasma NfL and p-tau181, along with established cerebrospinal fluid (CSF) biomarkers of AD pathology, were measured in participants with normal cognition (CN) and memory clinic patients with cognitive impairment (mild cognitive impairment and dementia, CI). Clinical and neuropsychological assessments were performed at inclusion and follow-up visits at 18 and 36 months. Multivariate analysis assessed associations of plasma NfL and p-tau181 levels with AD, single CSF biomarkers, hippocampal volume, and clinical measures of disease progression. Plasma NfL levels were higher in CN participants with an AD CSF profile (defined by a CSF p-tau181/Aβ <sub>1-42</sub> > 0.0779) as compared with CN non-AD, while p-tau181 plasma levels were higher in CI patients with AD. Plasma NfL levels correlated with CSF tau and p-tau181 in CN, and with CSF tau in CI patients. Plasma p-tau181 correlated with CSF p-tau181 in CN and with CSF tau, p-tau181, Aβ <sub>1-42</sub> , and Aβ <sub>1-42</sub> /Aβ <sub>1-40</sub> in CI participants. Compared with a reference model, adding plasma p-tau181 improved the prediction of AD in CI patients while adding NfL did not. Adding p-tau181, but not NfL levels, to a reference model improved prediction of cognitive decline in CI participants. Plasma NfL indicates neurodegeneration while plasma p-tau181 levels can serve as a biomarker of cerebral AD pathology and cognitive decline. Their predictive performance depends on the presence of cognitive impairment

Plasma neurofilament light and phosphorylated tau 181 as biomarkers of Alzheimer's disease pathology and clinical disease progression.

BACKGROUND: To assess the performance of plasma neurofilament light (NfL) and phosphorylated tau 181 (p-tau181) to inform about cerebral Alzheimer's disease (AD) pathology and predict clinical progression in a memory clinic setting. METHODS: Plasma NfL and p-tau181, along with established cerebrospinal fluid (CSF) biomarkers of AD pathology, were measured in participants with normal cognition (CN) and memory clinic patients with cognitive impairment (mild cognitive impairment and dementia, CI). Clinical and neuropsychological assessments were performed at inclusion and follow-up visits at 18 and 36 months. Multivariate analysis assessed associations of plasma NfL and p-tau181 levels with AD, single CSF biomarkers, hippocampal volume, and clinical measures of disease progression. RESULTS: Plasma NfL levels were higher in CN participants with an AD CSF profile (defined by a CSF p-tau181/Aβ1-42 > 0.0779) as compared with CN non-AD, while p-tau181 plasma levels were higher in CI patients with AD. Plasma NfL levels correlated with CSF tau and p-tau181 in CN, and with CSF tau in CI patients. Plasma p-tau181 correlated with CSF p-tau181 in CN and with CSF tau, p-tau181, Aβ1-42, and Aβ1-42/Aβ1-40 in CI participants. Compared with a reference model, adding plasma p-tau181 improved the prediction of AD in CI patients while adding NfL did not. Adding p-tau181, but not NfL levels, to a reference model improved prediction of cognitive decline in CI participants. CONCLUSION: Plasma NfL indicates neurodegeneration while plasma p-tau181 levels can serve as a biomarker of cerebral AD pathology and cognitive decline. Their predictive performance depends on the presence of cognitive impairment

Low-level grounding in a multimodal mobile service robot conversational system using graphical models

The main task of a service robot with a voice-enabled communication interface is to engage a user in dialogue providing an access to the services it is designed for. In managing such interaction, inferring the user goal (intention) from the request for a service at each dialogue turn is the key issue. In service robot deployment conditions speech recognition limitations with noisy speech input and inexperienced users may jeopardize user goal identification. In this paper, we introduce a grounding state-based model motivated by reducing the risk of communication failure due to incorrect user goal identification. The model exploits the multiple modalities available in the service robot system to provide evidence for reaching grounding states. In order to handle the speech input as sufficiently grounded (correctly understood) by the robot, four proposed states have to be reached. Bayesian networks combining speech and non-speech modalities during user goal identification are used to estimate probability that each grounding state has been reached. These probabilities serve as a base for detecting whether the user is attending to the conversation, as well as for deciding on an alternative input modality (e.g., buttons) when the speech modality is unreliable. The Bayesian networks used in the grounding model are specially designed for modularity and computationally efficient inference. The potential of the proposed model is demonstrated comparing a conversational system for the mobile service robot RoboX employing only speech recognition for user goal identification, and a system equipped with multimodal grounding.The evaluation experiments use component and system level metrics for technical (objective) and user-based (subjective) evaluation with multimodal data collected during the conversations of the robot RoboX with users