Very-high-frequency probes for atomic force microscopy with silicon optomechanics.

Atomic force microscopy (AFM) has been consistently supporting nanosciences and nanotechnologies for over 30 years and is used in many fields from condensed matter physics to biology. It enables the measurement of very weak forces at the nanoscale, thus elucidating the interactions at play in fundamental processes. Here, we leverage the combined benefits of micro/nanoelectromechanical systems and cavity optomechanics to fabricate a sensor for dynamic mode AFM at a frequency above 100 MHz. This frequency is two decades above the fastest commercial AFM probes, suggesting an opportunity for measuring forces at timescales unexplored thus far. The fabrication is achieved using very-large-scale integration technologies derived from photonic silicon circuits. The probe's optomechanical ring cavity is coupled to a 1.55 µm laser light and features a 130 MHz mechanical resonance mode with a quality factor of 900 in air. A limit of detection in the displacement of 3 × 10-16 m/√Hz is obtained, enabling the detection of the Brownian motion of the probe and paving the way for force sensing experiments in the dynamic mode with a working vibration amplitude in the picometer range. When inserted in a custom AFM instrument embodiment, this optomechanical sensor demonstrates the capacity to perform force-distance measurements and to maintain a constant interaction strength between the tip and sample, an essential requirement for AFM applications. Experiments indeed show a stable closed-loop operation with a setpoint of 4 nN/nm for an unprecedented subpicometer vibration amplitude, where the tip-sample interaction is mediated by a stretched water meniscus.

Psychometric validation of an Assessment Questionnaire on the Perception of and Adaptation to Visual Handicap in Adults (QUEPAHVA).

PURPOSE: Handicap evaluation in adults with acquired or progressive congenital visual loss allows for identification of the individual's specific needs and targeted therapy (medical, technical, rehabilitative and psychological). Currently, the subjective dimension of the handicap remains poorly explored in the field of visual loss. Our questionnaire aims to understand the whole of these subjective impacts. It differs from existing quality of life scales in ophthalmology in its approach centered on the process of adaptation, individual resources (technical, cognitive, psychic and environmental), and investigation of the perception of the handicap. The goal of the present study is to validate this questionnaire, which could be used in any adult with a visual handicap, regardless of the extent of the visual loss, its etiology, or the type of treatment or compensatory mechanisms. MATERIALS AND METHODS: The Assessment Questionnaire on the Perception of and Adaptation to Visual Handicap in Adults (QUEPAHVA) is composed of 28 items relating to perception of the visual impairment, its impact, and adaptive resources. They are divided into 3 sub-categories: Perception of daily life and relationships (10 items), Perception of visual status and compensatory mechanisms (8 items), and Psychological impact of the visual handicap (10 items). The responses are graded on a Likert scale. Factor analysis and verification of psychometric qualities were performed based on the responses of 446 subjects. The discriminatory validity of the NEI-VFQ 25 was proven with 99 subjects. Reliability over time (mean interval between T1 and T2=49.43 days) was measured in 31 subjects. Sensitivity to change between pre- and post-management (mean interval between T1 and T2=410 days) was tested in 123 subjects. RESULTS: Internal consistency was very good for the global scale (α=.90) as well as for the 3 sub-dimensions (α=.86; α=.79; α=.80). The discriminatory validity was satisfactory (r=.70). This result had to be interpreted as a function of the qualitative specificity of the questionnaire. The questionnaire enjoyed good reproducibility over time with regard to its total score and relatively satisfactory reproducibility with regard to its sub-dimensions. Sensitivity to change was very high and accounted for adaptations to the disability over time. CONCLUSION: The QUEPAHVA displays good psychometric qualities. It constitutes a new means of evaluation. Its potential applications are many. It permits evaluation of the needs of the individual and adaptation of the protocol of care. Its use in institutions may support a step forward in the science of evaluation and continued improvement in quality of care.

[Psychometric validation of an Assessment Questionnaire on the Perception of and Adaptation to Visual Handicap in Adults (QUEPAHVA). French translation of the article]. / Validation psychométrique d'un Questionnaire d'Évaluation de la Perception et de l'Adaptation au Handicap Visuel chez l'Adulte (QUEPAHVA).

PURPOSE: Handicap evaluation in adults with acquired or progressive congenital visual loss allows for identification of the individual's specific needs and targeted therapy (medical, technical, rehabilitative and psychological). Currently, the subjective dimension of the handicap remains poorly explored in the field of visual loss. Our questionnaire aims to understand the whole of these subjective impacts. It differs from existing quality of life scales in ophthalmology in its approach centered on the process of adaptation, individual resources (technical, cognitive, psychic and environmental), and investigation of the perception of the handicap. The goal of the present study is to validate this questionnaire, which could be used in any adult with a visual handicap, regardless of the extent of the visual loss, its etiology, or the type of treatment or compensatory mechanisms. MATERIALS AND METHODS: The Assessment Questionnaire on the Perception of and Adaptation to Visual Handicap in Adults (QUEPAHVA) is composed of 28 items relating to perception of the visual impairment, its impact, and adaptive resources. They are divided into 3 sub-categories: perception of daily life and relationships (10 items), Perception of visual status and compensatory mechanisms (8 items), and Psychological impact of the visual handicap (10 items). The responses are graded on a Likert scale. Factor analysis and verification of psychometric qualities were performed based on the responses of 446 subjects. The discriminatory validity of the NEI-VFQ 25 was proven with 99 subjects. Reliability over time (mean interval between T1 and T2=49.43 days) was measured in 31 subjects. Sensitivity to change between pre- and post-management (mean interval between T1 and T2=410 days) was tested in 123 subjects. RESULTS: Internal consistency was very good for the global scale (α=.90) as well as for the 3 sub-dimensions (α=.86; α=.79; α=.80). The discriminatory validity was satisfactory (r=.70). This result had to be interpreted as a function of the qualitative specificity of the questionnaire. The questionnaire enjoyed good reproducibility over time with regard to its total score and relatively satisfactory reproducibility with regard to its sub-dimensions. Sensitivity to change was very high and accounted for adaptations to the disability over time. CONCLUSION: The QUEPAHVA displays good psychometric qualities. It constitutes a new means of evaluation. Its potential applications are many. It permits evaluation of the needs of the individual and adaptation of the protocol of care. Its use in institutions may support a step forward in the science of evaluation and continued improvement in quality of care.

Microscopic Nanomechanical Dissipation in Gallium Arsenide Resonators.

We report on a systematic study of nanomechanical dissipation in high-frequency (≈300 MHz) gallium arsenide optomechanical disk resonators, in conditions where clamping and fluidic losses are negligible. Phonon-phonon interactions are shown to contribute with a loss background fading away at cryogenic temperatures (3 K). Atomic layer deposition of alumina at the surface modifies the quality factor of resonators, pointing towards the importance of surface dissipation. The temperature evolution is accurately fitted by two-level systems models, showing that nanomechanical dissipation in gallium arsenide resonators directly connects to their microscopic properties. Two-level systems, notably at surfaces, appear to rule the damping and fluctuations of such high-quality crystalline nanomechanical devices, at all temperatures from 3 to 300 K.

Theory of mind, empathy and emotion perception in cortical and subcortical neurodegenerative diseases.

Although the impact of neurodegenerative diseases on everyday interactions is well known in the literature, their impact on social cognitive processes remains unclear. The concept of social cognition refers to a set of skills, all of which are essential for living in a community. It involves social knowledge, perception and processing of social cues, and representation of mental states. This report is a review of recent findings on the impact of cortical and subcortical neurodegenerative diseases on three social cognitive processes, namely, the theory of mind, empathy and processing emotions. The focus here is on a conceptual approach to each of these skills and their cerebral underpinnings.

Discrepancy between social and nonsocial decision-making under uncertainty following prefrontal lobe damage: the impact of an interactionist approach.

Deficits in decision-making are thought to contribute significantly to socio-behavioral impairments of patients with frontal lobe damage. The purpose of this study was to test the hypothesis of whether the inappropriate social behavior of patients with frontal lesions can be viewed as the product of a general failure of decision-making ability or as the result of socio-cognitive impairment. We studied a group of patients with prefrontal lesions (FL patients, n = 15) and a group of matched healthy controls (n = 30) on the Iowa Gambling task (IGT) of nonsocial decision-making, environmental dependency phenomena (EDP) during social interaction, and the "reading the mind in the eyes" and "character intention task" of theory of mind (TOM) tasks. The FL patients were impaired in both TOM and EDP protocols but, surprisingly, they behaved appropriately in the IGT. In addition, FL patients with EDP did not differ in executive functioning, IGT and TOM measures from those who did not demonstrate these behavioral disorders. The right orbitofrontal cortex was associated with social decision-making deficits. By adopting an interactionist approach, this study raises the possibility of identifying components of social and nonsocial decision-making, which could be helpful in understanding the behavioral disorders of FL patients.

A Pipeline for the Generation of Realistic 3D Synthetic Echocardiographic Sequences: Methodology and Open-Access Database.

Quantification of cardiac deformation and strain with 3D ultrasound takes considerable research efforts. Nevertheless, a widespread use of these techniques in clinical practice is still held back due to the lack of a solid verification process to quantify and compare performance. In this context, the use of fully synthetic sequences has become an established tool for initial in silico evaluation. Nevertheless, the realism of existing simulation techniques is still too limited to represent reliable benchmarking data. Moreover, the fact that different centers typically make use of in-house developed simulation pipelines makes a fair comparison difficult. In this context, this paper introduces a novel pipeline for the generation of synthetic 3D cardiac ultrasound image sequences. State-of-the art solutions in the fields of electromechanical modeling and ultrasound simulation are combined within an original framework that exploits a real ultrasound recording to learn and simulate realistic speckle textures. The simulated images show typical artifacts that make motion tracking in ultrasound challenging. The ground-truth displacement field is available voxelwise and is fully controlled by the electromechanical model. By progressively modifying mechanical and ultrasound parameters, the sensitivity of 3D strain algorithms to pathology and image properties can be evaluated. The proposed pipeline is used to generate an initial library of 8 sequences including healthy and pathological cases, which is made freely accessible to the research community via our project web-page.

Impaired decision-making and brain shrinkage in alcoholism.

Alcohol-dependent individuals usually favor instant gratification of alcohol use and ignore its long-term negative consequences, reflecting impaired decision-making. According to the somatic marker hypothesis, decision-making abilities are subtended by an extended brain network. As chronic alcohol consumption is known to be associated with brain shrinkage in this network, the present study investigated relationships between brain shrinkage and decision-making impairments in alcohol-dependent individuals early in abstinence using voxel-based morphometry. Thirty patients performed the Iowa Gambling Task and underwent a magnetic resonance imaging investigation (1.5T). Decision-making performances and brain data were compared with those of age-matched healthy controls. In the alcoholic group, a multiple regression analysis was conducted with two predictors (gray matter [GM] volume and decision-making measure) and two covariates (number of withdrawals and duration of alcoholism). Compared with controls, alcoholics had impaired decision-making and widespread reduced gray matter volume, especially in regions involved in decision-making. The regression analysis revealed links between high GM volume in the ventromedial prefrontal cortex, dorsal anterior cingulate cortex and right hippocampal formation, and high decision-making scores (P<0.001, uncorrected). Decision-making deficits in alcoholism may result from impairment of both emotional and cognitive networks.

Executive functions in clinical and preclinical Alzheimer's disease.

Executive functions is an umbrella term describing a wide range of higher order processes that allow the flexible modification of thought and behaviour in response to changing cognitive or environmental contexts. Impairment of executive functions is common in neurodegenerative disorders such as Alzheimer's disease. These deficits negatively affect everyday activities and hamper the ability to cope with other cognitive or behavioural disorders. In this paper, we propose a synthesis of the knowledge on executive impairments in clinical and preclinical Alzheimer's disease, mostly leaning on the current studies made in this domain. We made some propositions for neuropsychological assessment of executive functions in preclinical and clinical phases of Alzheimer's disease. We hope that this overview will provide a useful insight into an area that is still insufficiently explored in the field of the neuropsychology of Alzheimer's disease.

3D strain assessment in ultrasound (Straus): a synthetic comparison of five tracking methodologies.

This paper evaluates five 3D ultrasound tracking algorithms regarding their ability to quantify abnormal deformation in timing or amplitude. A synthetic database of B-mode image sequences modeling healthy, ischemic and dyssynchrony cases was generated for that purpose. This database is made publicly available to the community. It combines recent advances in electromechanical and ultrasound modeling. For modeling heart mechanics, the Bestel-Clement-Sorine electromechanical model was applied to a realistic geometry. For ultrasound modeling, we applied a fast simulation technique to produce realistic images on a set of scatterers moving according to the electromechanical simulation result. Tracking and strain accuracies were computed and compared for all evaluated algorithms. For tracking, all methods were estimating myocardial displacements with an error below 1 mm on the ischemic sequences. The introduction of a dilated geometry was found to have a significant impact on accuracy. Regarding strain, all methods were able to recover timing differences between segments, as well as low strain values. On all cases, radial strain was found to have a low accuracy in comparison to longitudinal and circumferential components.

A contribution to the study of environmental dependency phenomena: the social hypothesis.

Environmental dependency phenomena refer to the symptoms initially described by Lhermitte (1983, 1984) under the terms of "utilization behavior" and "imitation behavior". These clinical signs are linked to essential notions such as free-will and human autonomy, and seem to be specific of the frontal pathology. Surprisingly, few studies have addressed these symptoms and inconsistent definitions are available. To investigate the theoretical and clinical definitions of environmental dependency phenomena, three groups of neurological patients (n=60) with frontal, subcortical, and posterior brain lesions were compared. Clinically, our findings help to rehabilitate the definitions of Lhermitte (1983, 1984) and challenge the classical interpretation in terms of an executive control deficit. The frontal specificity of the disorders and the lack of relation between executive/behavioral deficits were supported. The right orbitofrontal cortex seems particularly involved in environmental dependency. These results offer some evidences for differentiate two historical concepts of neuropsychology, namely the "frontal" and "dysexecutive" syndromes. A new interpretation of environmental dependency phenomena is provided which could be helpful to orient the neuropsychology of frontal syndrome.

Utilization behavior: clinical and theoretical approaches.

Lhermitte (1983) coined the term "utilization behavior" (UB) to define a neurobehavioral syndrome in which the visuo-tactile presentation of objects compels patients to grasp and use them, despite the fact that they have not been instructed to do so. The author suggested that UB was the consequence of frontal lobe damage. Thereafter, Shallice, Burgess, Schon, and Baxter (1989) questioned Lhermitte's (1983) procedure for eliciting UB, putting forward an alternative research methodology that led to differentiate two forms of UB: "induced" and "incidental." To date, there has been no direct comparison between these two procedures, nor have any other methodologies been used to explore this clinical sign, which is related to fundamental concepts such as free will and human autonomy. We investigated UB in 70 subjects (25 patients with frontal lobe lesions, 10 patients with posterior brain damage and 35 control subjects) using the methodologies of Lhermitte (1983) and Shallice et al. (1989), as well as an original "verbal generation" procedure. Our results show that the verbal generation procedure reveals UB efficiently and that elicitation of this sign appears to be directly linked to the content of the task. We discuss the interpretation of UB in terms of an executive control deficit.

Association of vitamin D deficiency with cognitive impairment in older women: cross-sectional study.

OBJECTIVE: The association between low serum 25-hydroxyvitamin D [25(OH)D] concentration and cognitive decline has been investigated by only a few studies, with mixed results. The objective of this cross-sectional population-based study was to examine the association between serum 25(OH)D deficiency and cognitive impairment while taking confounders into account. METHODS: The subjects, 752 women aged > or =75 years from the Epidémiologie de l'Ostéoporose (EPIDOS) cohort, were divided into 2 groups according to serum 25(OH)D concentrations (either deficient, <10 ng/mL, or nondeficient, > or =10 ng/mL). Cognitive impairment was defined as a Pfeiffer Short Portable Mental State Questionnaire (SPMSQ) score <8. Age, body mass index, number of chronic diseases, hypertension, depression, use of psychoactive drugs, education level, regular physical activity, and serum intact parathyroid hormone and calcium were used as potential confounders. RESULTS: Compared with women with serum 25(OH)D concentrations > or =10 ng/mL (n = 623), the women with 25(OH)D deficiency (n = 129) had a lower mean SPMSQ score (p < 0.001) and more often had an SPMSQ score <8 (p = 0.006). There was no significant linear association between serum 25(OH)D concentration and SPMSQ score (beta = -0.003, 95% confidence interval -0.012 to 0.006, p = 0.512). However, serum 25(OH)D deficiency was associated with cognitive impairment (crude odds ratio [OR] = 2.08 with p = 0.007; adjusted OR = 1.99 with p = 0.017 for full model; and adjusted OR = 2.03 with p = 0.012 for stepwise backward model). CONCLUSIONS: 25-Hydroxyvitamin D deficiency was associated with cognitive impairment in this cohort of community-dwelling older women.

Vitamin D and cognitive performance in adults: a systematic review.

Chronic low serum 25-hydroxyvitamin D (25OHD) concentrations are common in adults and are associated with numerous non-skeletal diseases. Vitamin D receptors (VDR) are located in the human cortex and hippocampus, which are key areas for cognition. The objective of this study was to systematically review all published data from the past 30 years which examined the association between serum 25OHD concentrations and cognitive performance in adults. An English and French Medline, PsycINFO and Cochrane Library search ranging from 1979 to 2008 indexed under the Medical Subject Heading (MeSH) terms 'Vitamin D' or 'Hydroxycholecalciferols' combined with the terms 'Dementia' or 'Cognition' or 'Cognition Disorders' or 'Delirium' or 'Memory' or 'Memory Disorders' or 'Orientation' or 'Executive Functions' or 'Attention' or 'Brain' or 'Neuropsychological Tests' was performed. Of the 99 selected studies, five observational studies met the selection criteria and were included in the final analysis. No prospective cohort study was found. The number of participants ranged from 32 to 9556 community-dwelling older adults (45-65% women). Three studies showed four significant positive associations between serum 25OHD concentrations and global cognitive functions, whereas three other studies exploring specific aspects of cognition showed 11 non-significant associations. This systematic review shows that the association between serum 25OHD concentrations and cognitive performance is not yet clearly established. The inconclusive results of the reviewed studies could be due to methodology, types of the cognitive tasks used and/or the cellular mechanisms of vitamin D.

[Frontal lobe, executive functions and cognitive control]. / Lobe frontal, fonctions exécutives et controle cognitif.

The approach of executive functions began with the early description of behavioural disorders induced by frontal damage. The development of neuropsychology has led to the description of a large variety of cognitive disorders. The interpretation in cognitive terms of these disorders has emphasized the critical impairment of executive functions which are involved in non-routine situations. The role of working memory, initially suggested by animal studies, has also largely influenced theoretical approaches. Numerous studies have been interpreted within the theoretical frameworks developed by Shallice and by Baddeley. A large amount of studies have allowed the specification of control processes (initiation, inhibition...). Recent studies are beginning to investigate cognitive disorders underlying behavioural changes such as deficits of emotional, social and metacognitive processes. In addition these studies seriously question the assumption of a unique central control system. These studies have deeply influenced the clinical approach, the assessment and the diagnosis of executive syndrome. For clinical practice, these data lead to favour specific assessment of some key behavioural and cognitive deficits based on a battery of tests and structured interview of an informant.

Assessment of left ventricular mass and volumes by three-dimensional echocardiography in patients with or without wall motion abnormalities: comparison against cine magnetic resonance imaging.

AIM: To evaluate if three-dimensional echocardiography (3-DE) is as accurate and reproducible as cine magnetic resonance imaging (cMR) in estimating left ventricular (LV) parameters in patients with and without wall motion abnormalities (WMA). METHODS: 83 patients (33 with WMA) underwent 3-DE and cMR. 3-DE datasets were analysed using a semi-automatic contour detection algorithm. The accuracy of 3-DE was tested against cMR in the two groups of patients. All measurements were made twice by two different observers. RESULTS: LV mass by 3-DE was similar to that obtained by cMR (149 (SD 42) g vs 148 (45) g, p = 0.67), with small bias (1 (28) g) and excellent interobserver agreement (-2 (31) g vs 4 (26) g). The two measurements were also highly correlated (r = 0.94), irrespective of WMA. End-diastolic and end-systolic LV volumes and ejection fraction by 3-DE and cMR were highly correlated (r = 0.97, 0.98, 0.94, respectively). Yet, 3-DE underestimated cMR end-diastolic volumes (167 (68) ml vs 187 (70) ml, p<0.001) and end-systolic volumes (88 (56) ml vs 101 (65) ml, p<0.001), but yielded similar ejection fractions (50% (14%) vs 50% (16%), p = 0.23). CONCLUSION: 3-DE permits accurate determination of LV mass and volumes irrespective of the presence or absence of WMA. LV parameters obtained by 3-DE are also as reproducible as those obtained by cMR. This suggests that 3-DE can be used to follow up patients with LV hypertrophy and/or remodelling.

Cognitive changes in asymptomatic carriers of the Huntington disease mutation gene.

Huntington disease (HD) is a neurodegenerative disorder due to an excessive number of CAG repeats in the IT15 gene on chromosome 4. Studies of cognitive function in asymptomatic gene carriers have yielded contradictory results. This study compared cognitive performance in 44 subjects with the HD mutation (group of carriers) who had no clinical signs of HD and 39 at-risk individuals without HD mutation (group of non-carriers). Neuropsychological evaluation focused on global cognitive efficiency, psychomotor speed, attentional, executive and memory functions. Significant differences, with lower performances in the group of gene carriers, were detected for some measures of psychomotor speed, attention and executive functioning (all P < 0.01). More differences between groups were observed for memory measures, in particular on the California Verbal Memory Test. Complementing these observations, cognitive scores were correlated with age in the group of gene carriers, but not in the group of non-carriers. This suggests that the cognitive changes precede the appearance of the motor and psychiatric symptoms in HD and that tests proved to be sensitive to early HD deficiencies are better suited than global cognitive efficiency scales to observe them.

[A study of action planning in patients with Alzheimer's disease using the zoo map test]. / Etude de la planification de l'action au moyen du test du plan du zoo dans la maladie d'Alzheimer.

INTRODUCTION: Executive dysfunction is regularly reported in patients with Alzheimer's disease. Nevertheless few studies have focused on planning ability in this neurodegenerative disease. OBJECTIVES: This study aimed to investigate the formulation and the execution of plans in Alzheimer's disease using an ecological planning subtask derived from the Behavioural Assessment of the Dysexecutive Syndrome test battery, the "Zoo Map Test". There are two trials. The first trial consists of a "high demand" version of the subtask in which the subjects must plan in advance the order in which they will visit designated locations in a zoo (formulation level). In the second, or "low demand" version, the subject is simply required to follow a concrete externally imposed strategy to reach the locations to visit (execution level). The test was given to 16 patients with Alzheimer's disease and 13 normal elderly subjects. RESULTS: The two way ANOVAs mainly showed more difficulties in patients with Alzheimer's disease than in healthy elderly in both conditions. The difference between formulation and execution was greater in patients with Alzheimer's disease than in healthy elderly. Planning impairments mainly correlated with behavioural changes (in particular motivational changes) observed by patient's relatives. CONCLUSION: These results suggest that patients with Alzheimer's disease have some problems to mentally develop logical strategies and to execute complex predetermined plans, which are partially related to behavioural changes.

What about theory of mind after severe brain injury?

BACKGROUND: Behavioural changes are often reported after a severe traumatic brain injury (TBI). These changes are usually a greater burden for relatives than physical or cognitive impairments. This study investigated social cognition in TBI patients using two theory of mind (TOM) tasks. METHOD: The performances of 17 patients with severe TBI and 17 matched controls were compared on two tasks designed to investigate understanding of other people's mental states: The 'Reading the Mind in the Eyes' test (RME) and the 'Character Intention Task' (CIT). TBI patients and controls were also given several executive function tasks. RESULTS: Compared to healthy controls, patients were impaired in most executive tests and in both TOM tasks. No relationship was found between TOM and executive measures. This is consistent with Rowe's position, who suggested an independence between executive functioning and social cognition. These data suggest that TBI patients may have specific social intelligence disturbances. CONCLUSION: Future work should employ additional tests of TOM and behavioural ratings and recruit more patients in order to complete analysis.