Sense of agency disturbances in movement disorders: A comprehensive review

Sense of agency refers to the experience that one’s self-generated action causes an event in the external environment. Here, we review the behavioural and brain evidence of aberrant experiences of agency in movement disorders, clinical conditions characterized by either a paucity or an excess of movements unrelated to the patient’s intention. We show that specific abnormal agency experiences characterize several movement disorders. Those manifestations are typically associated with structural and functional brain abnormalities. However, the evidence is sometimes conflicting, especially when considering results obtained through different agency measures. The present review aims to create order in the existing literature on sense of agency investigations in movement disorders and to provide a coherent overview framed within current neurocognitive models of motor awareness

Cancer Niches and Their Kikuchi Free Energy

Biological forms depend on a progressive specialization of pluripotent stem cells. The differentiation of these cells in their spatial and functional environment defines the organism itself; however, cellular mutations may disrupt the mutual balance between a cell and its niche, where cell proliferation and specialization are released from their autopoietic homeostasis. This induces the construction of cancer niches and maintains their survival. In this paper, we characterise cancer niche construction as a direct consequence of interactions between clusters of cancer and healthy cells. Explicitly, we evaluate these higher-order interactions between niches of cancer and healthy cells using Kikuchi approximations to the free energy. Kikuchi’s free energy is measured in terms of changes to the sum of energies of baseline clusters of cells (or nodes) minus the energies of overcounted cluster intersections (and interactions of interactions, etc.). We posit that these changes in energy node clusters correspond to a long-term reduction in the complexity of the system conducive to cancer niche survival. We validate this formulation through numerical simulations of apoptosis, local cancer growth, and metastasis, and highlight its implications for a computational understanding of the etiopathology of cancer

Effect of metal clusters on the swelling of gold-fluorocarbon-polymer composite films

We have investigated the phenomenon of swelling due to acetone diffusion in fluorocarbon polymer films doped with different gold concentrations below the percolation threshold. The presence of the gold clusters in the polymer is shown to improve the mixing between the fluorocarbon polymer and the acetone, which is not a good solvent for this kind of polymers. In order to explain the experimental results the stoichiometry and the morphology of the polymer--metal system have been studied and a modified version of the Flory--Huggins model has been developed

Resting sympathetic baroreflex sensitivity in subjects with low and high tolerance to central hypovolemia induced by lower body negative pressure

Central hypovolemia elicited by orthostasis or hemorrhage triggers sympathetically-mediated baroreflex responses to maintain organ perfusion; these reflexes are less sensitive in patients with orthostatic intolerance, and during conditions of severe blood loss, may result in cardiovascular collapse (decompensatory or circulatory shock). The ability to tolerate central hypovolemia is variable and physiological factors contributing to tolerance are emerging. We tested the hypothesis that resting muscle sympathetic nerve activity (MSNA) and sympathetic baroreflex sensitivity (BRS) are attenuated in male and female subjects who have low tolerance (LT) to central hypovolemia induced by lower body negative pressure (LBNP). MSNA and diastolic arterial pressure (DAP) were recorded in 47 human subjects who subsequently underwent LBNP to tolerance (onset of presyncopal symptoms). LT subjects experienced presyncopal symptoms prior to completing LBNP of -60 mm Hg, and subjects with high tolerance (HT) experienced presyncopal symptoms after completing LBNP after -60 mmHg. Contrary to our hypothesis, resting MSNA burst incidence was not different between LT and HT subjects, and was not related to time to presyncope. BRS was assessed as the slope of the relationship between spontaneous fluctuations in DAP and MSNA during 5 min of supine rest. MSNA burst incidence/DAP correlations were greater than or equal to 0.5 in 37 subjects (LT: n= 9; HT: n=28), and BRS was not different between LT and HT (-1.8 ± 0.3 vs. -2.2 ± 0.2 bursts•(100 beats)-1•mmHg-1, p=0.29). We conclude that tolerance to central hypovolemia is not related to either resting MSNA or sympathetic BRS

Heart Rate Variability during Simulated Hemorrhage with Lower Body Negative Pressure in High and Low Tolerant Subjects

Heart rate variability (HRV) decreases during hemorrhage, and has been proposed as a new vital sign to assess cardiovascular stability in trauma patients. The purpose of this study was to determine if any of the HRV metrics could accurately distinguish between individuals with different tolerance to simulated hemorrhage. Specifically, we hypothesized that (1) HRV would be similar in low tolerant (LT) and high tolerant (HT) subjects at presyncope when both groups are on the verge of hemodynamic collapse; and (2) HRV could distinguish LT subjects at presyncope from hemodynamically stable HT subjects (i.e., at a submaximal level of hypovolemia). Lower body negative pressure (LBNP) was used as a model of hemorrhage in healthy human subjects, eliciting central hypovolemia to the point of presyncopal symptoms (onset of hemodynamic collapse). Subjects were classified as LT if presyncopal symptoms occurred during the −15 to −60 mmHg levels of LBNP, and HT if symptoms occurred after LBNP of −60 mmHg. A total of 20 HRV metrics were derived from R–R interval measurements at the time of presyncope, and at one level prior to presyncope (submax) in LT and HT groups. Only four HRV metrics (Long-range Detrended Fluctuation Analysis, Forbidden Words, Poincaré Plot Descriptor Ratio, and Fractal Dimensions by Curve Length) supported both hypotheses. These four HRV metrics were evaluated further for their ability to identify individual LT subjects at presyncope when compared to HT subjects at submax. Variability in individual LT and HT responses was so high that LT responses overlapped with HT responses by 85–97%. The sensitivity of these HRV metrics to distinguish between individual LT from HT subjects was 6–33%, and positive predictive values were 40–73%. These results indicate that while a small number of HRV metrics can accurately distinguish between LT and HT subjects using group mean data, individual HRV values are poor indicators of tolerance to hypovolemia

Hemodynamic and ADH responses to central blood volume shifts in cardiac-denervated humans

Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes designed to induce blood volume shifts in ten cardiac transplant recipients to assess the contribution of cardiac and vascular volume receptors in the control of ADH secretion. Each subject underwent 15 min of a control period in the seated posture, then assumed a lying posture for 30 min at 6 deg head down tilt (HDT) followed by 20 min of seated recovery. Venous blood samples and cardiac dimensions (echocardiography) were taken at 0 and 15 min before HDT, 5, 15, and 30 min of HDT, and 5, 15, and 30 min of seated recovery. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Resting plasma volume (PV) was measured by Evans blue dye and percent changes in PV during posture changes were calculated from changes in hematocrit. Heart rate (HR) and blood pressure (BP) were recorded every 2 min. Results indicate that cardiac volume receptors are not the only mechanism for the control of ADH release during acute blood volume shifts in man

Gender differences in endocrine responses to posture and 7 days of 6 deg head down bed rest

Endocrine regulation of fluids and electrolytes during seven days of 6 deg head down bed rest (HDBR) was compared in male (n = 8) and, for the first time, female (n = 8) volunteers. The subjects' responses to quiet standing for 2 hr before and after HDBR were also tested. In both sexes, diuresis and natriuresis were evident during the first 2-3 days of HDBR, resulting in a marked increase in the urinary Na/K ratio and significant Na retention on reambulation. After the first day of HDBR, plasma renin activity (PRA) was increased relative to aldosterone, plasma volume was decreased, and the renal response to aldosterone appeared to be appropriate. Circulating levels of arginine vasopressin (AVP), cortisol, and ACTH were unchanged during HDBR. Plasma testosterone decreased slightly on day 2 of HDBR in males. The ratio of AM ACTH to cortisol was lower in females than in males because ACTH was lower in females. Urinary cortisol increased and remained elevated throughout the HDBR in males only. There were no gender differences in the responses to 7 day HDBR, except those in the pituitary-adrenal system; those differences appeared unrelated to the postural change. The provocative cardiovascular test of quiet standing before and after bed rest revealed both sex differences and effects of HDBR. There were significant sex differences in cardiovascular responses to standing, before and after HDBR. Females had greater PRA and aldosterone responses to standing before bedrest and larger aldosterone responses to standing after HDBR than males. Cardiovascular responses to standing before and after bedrest differed markedly: arterial pressure and heart rates increased with standing before HDBR, by contrast, arterial pressure decreased, with greater increases in heart rates after HDBR. In both sexes, all hormonal responses to standing were greater after HDBR. The results show clearly that similar responses to standing as well as to HDBR occur in both sexes, but that females exhibit greater PRA and aldosterone responses than males

Sympathetic Responses to Central Hypovolemia: New Insights from Microneurographic Recordings

Hemorrhage remains a major cause of mortality following traumatic injury in both military and civilian settings. Lower body negative pressure (LBNP) has been used as an experimental model to study the compensatory phase of hemorrhage in conscious humans, as it elicits central hypovolemia like that induced by hemorrhage. One physiological compensatory mechanism that changes during the course of central hypovolemia induced by both LBNP and hemorrhage is a baroreflex-mediated increase in muscle sympathetic nerve activity (MSNA), as assessed with microneurography. The purpose of this review is to describe recent results obtained using microneurography in our laboratory as well as those of others that have revealed new insights into mechanisms underlying compensatory increases in MSNA during progressive reductions in central blood volume and how MSNA is altered at the point of hemodynamic decompensation. We will also review recent work that has compared direct MSNA recordings with non-invasive surrogates of MSNA to determine the appropriateness of using such surrogates in assessing the clinical status of hemorrhaging patients

Effect of Chemical Vapor Deposition WS2 on Viability and Differentiation of SH-SY5Y Cells

In recent years, transition metal dichalcogenides have been attracting an increasing interest in the biomedical field, thus implying the need of a deeper understanding of their impact on cell behavior. In this study we investigate tungsten disulfide (WS2) grown via chemical vapor deposition (CVD) on a transparent substrate (sapphire) as a platform for neural-like cell culture. We culture SH-SY5Y human neuroblastoma cells on WS2, using graphene, sapphire and standard culture well as controls. The quality, thickness and homogeneity of the materials is analyzed using atomic force microscopy and Raman spectroscopy. The cytocompatibility of CVD WS2 is investigated for the first time by cell viability and differentiation assessment on SH-SY5Y cells. We find that cells differentiated on WS2, displaying a viability and neurite length comparable with the controls. These findings shine light on the possibility of using WS2 as a cytocompatible material for interfacing neural cells