Economic issues provokes hazardous landing decision-making by enhancing the activity of "emotional" neural pathways

The analysis of aeronautical accidents highlights the fact that some airline pilots demonstrate a trend to land whereas the approach is not well stabilized. This behavior seems to be the consequence of various factors, including financial issues. Our hypothesis is that financial constraints modulate the brain circuitry of emotion and reward, in particular via the interactions between two prefrontal structures: the dorsolateral prefrontal cortex(DLPFC), main center of the executive functions (EFs), high level cognitive abilities, and the ventromedial prefrontal cortex (VMPFC), structure linked with the limbic system, major substratum of emotional processes. In our experiment, participants performed a simplified task of landing in which the level of uncertainty and the financial incentive were manipulated. A preliminary behavioral experiment (n = 12) was conducted. A similar second experiment using functional magnetic resonance imaging (fMRI) is in progress and a case study only is reported here. The behavioral data showed that the participants made more risky decision to land in the financial incentive condition in comparison to the neutral condition, where no financial incentive was delivered. This was particularly true when the uncertainty was high. The functional neuroimaging results showed that the reasoning performed in neutral condition resulted in enhanced activity in DLPFC. On the contrary, under the influence of the financial incentive, VMPFC activity was increased. These results showed the effectiveness of the financial incentive to bias decision-making toward a more risky and less rational behavior from a safety point of view. Functional neuroimaging data showed a shift from cold to hot reasoning in presence of the financial incentive, suggesting that pilot erroneous trend to land could be explained by a temporary perturbation of the decision-making process due to the negative emotional consequences associated with the go-around

Neuroimaging and Neurolaw: Drawing the Future of Aging

Human brain-aging is a complex, multidimensional phenomenon. Knowledge of the numerous aspects that revolve around it is therefore essential if not only the medical issues, but also the social, psychological, and legal issues related to this phenomenon are to be managed correctly. In the coming decades, it will be necessary to find solutions to the management of the progressive aging of the population so as to increase the number of individuals that achieve successful aging. The aim of this article is to provide a current overview of the physiopathology of brain aging and of the role and perspectives of neuroimaging in this context. The progressive development of neuroimaging has opened new perspectives in clinical and basic research and it has modified the concept of brain aging. Neuroimaging will play an increasingly important role in the definition of the individual's brain aging in every phase of the physiological and pathological process. However, when the process involved in age-related brain cognitive diseases is being investigated, factors that might affect this process on a clinical and behavioral level (genetic susceptibility, risks factors, endocrine changes) cannot be ignored but must, on the contrary, be integrated into a neuroimaging evaluation to ensure a correct and global management, and they are therefore discussed in this article. Neuroimaging appears important to the correct management of age-related brain cognitive diseases not only within a medical perspective, but also legal, according to a wider approach based on development of relationship between neuroscience and law. The term neurolaw, the neologism born from the relationship between these two disciplines, is an emerging field of study, that deals with various issues in the impact of neurosciences on individual rights. Neuroimaging, enhancing the detection of physiological and pathological brain aging, could give an important contribution to the field of neurolaw in elderly where the full control of cognitive and volitional functions is necessary to maintain a whole series of rights linked to legal capacity. For this reason, in order to provide the clinician and researcher with a broad view of the brain-aging process, the role of neurolaw will be introduced into the brain-aging context

Intracranial fluids dynamics alterations and cortical thickness

Objectives: The issue of cortical atrophy is important in normal aging and disease since it is associated with cognitive and physical impairments. Cortical atrophy is potentially a relevant biomarker for the early diagnosis of Alzheimer’s disease (AD). The vascular component is also an integral part of AD and other late-life neurodegenerative diseases. Abnormalities in blood flow appear before accumulation of abnormal proteins in AD. The occlusion of capillaries by neutrophils are significantly higher in AD animal models than control and reduction of those occlusions with an antibody increases both blood flow and cognitive capacities. Vascular alterations lead to hypoperfusion, oxidative stress and inflammation, which in turn lead to damage of neurons, glia and myelin, predominantly in the white mater. Implication of vascular pathologies for gray matter remains unclear. A recent study showed that altered cerebral hemodyamics in asymptomatic carotid artery stenosis is associated with cortical thinning. However there is no proven link between vascular pathologies and cortical thinning. We propose to explore brain aging with a combined biomechanical and imaging approach in order to assess both fluid dynamics alterations and brain structural modifications. We hypothesize that there is a link between altered cerebral hemodynamics and loss of cortical thickness during brain aging. Methods: 80 patients suspected of hydrocephalus were prospectively involved. All patients complain of gait alteration, urinary difficulties, mild apathy and ventriculomegaly on brain imaging. They all underwent brain MRI with T1 weighted images to quantify cortical thickness and phase contrast images to measure arterial, venous and CSF velocities. Lumbar infusion test was also performed to gauge lumbar pressure, a surrogate marker of intracranial pressure (ICP), and CSF dynamics. The cortical volumetric segmentation was done by an automatic post-processing analysis with FREESURFER and local thicknesses were assessed with CorThiZon. Venous, arterial and CSF velocities were measured from PCMRI with BIOFLOWIMAGE software. ICP and CSF dynamics were extracted form infusion tests. Pearson correlations were calculated between cortical thickness and arterial, venous and CSF velocities, but also ICP and derived indices. Results: Mean cortical thickness is positively correlated with mean ICP (r=0.48, p=0.001), ICP pulse amplitude (r=0.43, p=0.001), arterial flow (r=0.44, p=0.001), aqueductal CSF flow(r=046, p=0.001), but negatively correlates with venous flow (r=-0.44, p=0.001). Conclusions: We demonstrate that cortical thickness is correlated with arterial and CSF pulsatility. The causality is more complex since it involves local microcirculation that could not be directly measured. However the association between intracranial pulsatility and gray matter thickness suggests that there is a relationship between vascular alterations at the macroscale level and the pathobiology of cortical atrophy

Clinical heterogeneity of neuro-inflammatory PET profiles in early Alzheimer’s disease

The relationship between neuroinflammation and cognition remains uncertain in early Alzheimer’s disease (AD). We performed a cross-sectional study to assess how neuroinflammation is related to cognition using TSPO PET imaging and a multi-domain neuropsychological assessment. A standard uptake value ratio (SUVR) analysis was performed to measure [18F]-DPA-714 binding using the cerebellar cortex or the whole brain as a (pseudo)reference region. Among 29 patients with early AD, the pattern of neuroinflammation was heterogeneous and exhibited no correlation with cognition at voxel-wise, regional or whole-brain level. The distribution of the SUVR values was independent of sex, APOE phenotype, early and late onset of symptoms and the presence of cerebral amyloid angiopathy. However, we were able to demonstrate a complex dissociation as some patients with similar PET pattern had opposed neuropsychological profiles while other patients with opposite PET profiles had similar neuropsychological presentation. Further studies are needed to explore how this heterogeneity impacts disease progression

Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study)

Background: Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4–20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD. Also, recent scientific data has emphasized the importance of immuno-inflammatory pathways in the pathophysiology of MDD. The lack of data on the magnitude of brain neuroinflammation in MDD is the main limitation of this inflammatory hypothesis. Our team has previously demonstrated the relevance of [18F] DPA-714 as a neuroinflammation biomarker in humans. We formulated the following hypotheses for the current study: (i) Neuroinflammation in MDD can be measured by [18F] DPA-714; (ii) its levels are associated with clinical severity; (iii) it is accompanied by anatomical and functional alterations within the frontal-subcortical circuits; (iv) it is a marker of treatment resistance.Methods: Depressed patients will be recruited throughout 4 centers (Bordeaux, Montpellier, Tours, and Toulouse) of the French network from 13 expert centers for resistant depression. The patient population will be divided into 3 groups: (i) experimental group—patients with current MDD (n = 20), (ii) remitted depressed group—patients in remission but still being treated (n = 20); and, (iii) control group without any history of MDD (n = 20). The primary objective will be to compare PET data (i.e., distribution pattern of neuroinflammation) between the currently depressed group and the control group. Secondary objectives will be to: (i) compare neuroinflammation across groups (currently depressed group vs. remitted depressed group vs. control group); (ii) correlate neuroinflammation with clinical severity across groups; (iii) correlate neuroinflammation with MRI parameters for structural and functional integrity across groups; (iv) correlate neuroinflammation and peripheral markers of inflammation across groups.Discussion: This study will assess the effects of antidepressants on neuroinflammation as well as its role in the treatment response. It will contribute to clarify the putative relationships between neuroinflammation quantified by brain neuroimaging techniques and peripheral markers of inflammation. Lastly, it is expected to open innovative and promising therapeutic perspectives based on anti-inflammatory strategies for the management of treatment-resistant forms of MDD commonly seen in clinical practice.Clinical trial registration (reference: NCT03314155): https://www.clinicaltrials.gov/ct2/show/NCT03314155?term=neuroinflammation&cond=depression&cntry=FR&rank=

Paroxetine-induced modulation of cortical activity supporting language representations of action

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Verb and noun generation tasks in Huntington's disease

International audienceAbstract We compared noun‐ and verb‐generation tasks in a demented group (n = 9, Dementia Rating Scale ≤ 129) and in a non‐demented group (n = 17, Dementia Rating Scale > 129) of Huntington's disease (HD) patients compared to 26 matched normal subjects. We did not find a specific deficit for verb production in non‐demented patients who had a performance similar to but weaker than that of the controls across the four tasks. The profile of results was different in the demented group because, apart from a global deficit whatever the task in comparison with both non‐demented and control groups, the demented patients exhibited increased difficulties in the two tasks implying verb production. The deficit of verb production observed in demented HD patients is discussed in relation to the damage to the motor loop in HD patients at later stages of disease. © 2003 Movement Disorder Societ

A PET study of word generation in Huntington’s disease: Effects of lexical competition and verb/noun category

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High-Field Neuroimaging in Parkinson’s Disease

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The effects of emotion on pilot decision-making: A neuroergonomic approach to aviation safety

International audienceEmotion or stress can jeopardize decision-making relevance and cognitive functioning. In this paper we examine plan continuation error (PCE), an erroneous behavior defined as a "failure to revise a flight plan despite emerging evidence that suggests it is no longer safe" (Orasanu, Ames, Martin, & Davison, 2001). Our hypothesis is that negative emotional consequences attached to the go-around decision provoke a temporary impairment of the decision-making process and favor PCE. We investigated this hypothesis with a simplified landing task in which two possible contributors to those emotions, namely the uncertainty of a decision outcome and the reward/punishment, associated to the outcome were manipulated. A behavioral experiment (n = 12) and a second one (n = 6) using functional magnetic resonance imaging (fMRI) were conducted. Behavioral results of both studies showed the effectiveness of the financial incentive to bias decision making toward a more risky and less rational behavior from a safety point of view. Neuroimaging data showed that the PCE behavior was underpinned by the contribution of brain circuitry of emotion and reward during the decision-making process. Taken together, behavioral and fMRI result support the hypothesis that PCE can be provoked by a temporary impairment of rational decisio