Disentangling the effects of age and mild traumatic brain injury on brain network connectivity:A resting state fMRI study

INTRODUCTION: Cognitive complaints are common shortly after mild traumatic brain injury (mTBI) but may persist up to years. Age-related cognitive decline can worsen these symptoms. However, effects of age on mTBI sequelae have scarcely been investigated. METHODS: Fifty-four mTBI patients (median age: 35 years, range 19-64 years, 67% male) and twenty age- and sex-matched healthy controls were studied using resting state functional magnetic resonance imaging in the sub-acute phase. Independent component analysis was used to identify intrinsic connectivity networks (ICNs). A multivariate approach was adopted to evaluate the effects of age and group on the ICNs in terms of (static) functional network connectivity (FNC), intensities of spatial maps (SMs) and time-course spectral power (TC). RESULTS: We observed significant age-related changes for a) FNC: changes between 10 pairs of ICNs, mostly involving the default mode (DM) and/or the cognitive-control (CC) domains; b) SMs: intensity decrease in clusters across three domains and intensity increase in clusters across two domains, including the CC but not the DM and c) TC: spectral power decrease within the 0-0.15 Hz range and increase within the 0.20-0.25 Hz range for increasing age within networks located in frontal areas, including the anterior DM. Groups only differed for TC within the 0.065-0.10 Hz range in the cerebellar ICN and no age × group interaction effect was found. CONCLUSIONS: We showed robust effects of age on connectivity between and within ICNs that are associated with cognitive functioning. Differences between mTBI patients and controls were only found for activity in the cerebellar network, increasingly recognized to participate in cognition. Our results suggest that to allow for capturing the true effects related to mTBI and its effects on cognitive functioning, age should be included as a covariate in mTBI studies, in addition to age-matching groups

The broad differential diagnosis of encephalitis:a case report

A 31-year-old previously healthy woman presented with hallucinations and altered mental status, which was eventually found to be due to anti-N-methyl-D-aspartate receptor encephalitis. In this case report, we discuss the broad differential diagnosis of encephalitis with infectious and autoimmune causes. Furthermore, we consider empirical treatment options in case a definite diagnosis is hard to be made

The chronnectome as a model for Charcot's 'dynamic lesion' in functional movement disorders

This exploratory study set out to investigate dynamic functional connectivity (dFC) in patients with jerky and tremulous functional movement disorders (JT-FMD). The focus in this work is on dynamic brain states, which represent distinct dFC patterns that reoccur in time and across subjects. Resting-state fMRI data were collected from 17 patients with JT-FMD and 17 healthy controls (HC). Symptom severity was measured using the Clinical Global Impression-Severity scale. Depression and anxiety were measured using the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), respectively. Independent component analysis was used to extract functional brain components. After computing dFC, dynamic brain states were determined for every subject using k-means clustering. Compared to HC, patients with JT-FMD spent more time in a state that was characterized predominantly by increasing medial prefrontal, and decreasing posterior midline connectivity over time. They also tended to visit this state more frequently. In addition, patients with JT-FMD transitioned significantly more often between different states compared to HC, and incorporated a state with decreasing medial prefrontal, and increasing posterior midline connectivity in their attractor, i.e., the cyclic patterns of state transitions. Altogether, this is the first study that demonstrates altered functional brain network dynamics in JT-FMD that may support concepts of increased self-reflective processes and impaired sense of agency as driving factors in FMD

Neuromuscular Blockade with Rocuronium Bromide Increases the Tolerance of Acute Normovolemic Anemia in Anesthetized Pigs

Background: The patient's individual anemia tolerance is pivotal when blood transfusions become necessary, but are not feasible for some reason. To date, the effects of neuromuscular blockade (NMB) on anemia tolerance have not been investigated. Methods: 14 anesthetized and mechanically ventilated pigs were randomly assigned to the Roc group (3.78 mg/kg rocuronium bromide followed by continuous infusion of 1 mg/kg/min, n = 7) or to the Sal group (administration of the corresponding volume of normal saline, n = 7). Subsequently, acute normovolemic anemia was induced by simultaneous exchange of whole blood for a 6% hydroxyethyl starch solution (130/0.4) until a sudden decrease of total body O-2 consumption (VO2) indicated a critical limitation of O-2 transport capacity. The Hb concentration quantified at this time point (Hb(crit)) was the primary end-point of the protocol. Secondary endpoints were parameters of hemodynamics, O-2 transport and tissue oxygenation. Results: Hb(crit) was significantly lower in the Roc group (2.4 +/- 0.5 vs. 3.2 +/- 0.7 g/dl) reflecting increased anemia tolerance. NMB with rocuronium bromide reduced skeletal muscular VO2 and total body O-2 extraction rate. As the cardiac index increased simultaneously, total body VO2 only decreased marginally in the Roc group (change of VO2 relative to baseline -1.7 +/- 0.8 vs. 3.2 +/- 1.9% in the Sal group, p < 0.05). Conclusion: Deep NMB with rocuronium bromide increases the tolerance of acute normovolemic anemia. The underlying mechanism most likely involves a reduction of skeletal muscular VO2. During acellular treatment of an acute blood loss, NMB might play an adjuvant role in situations where profound stages of normovolemic anemia have to be tolerated (e.g. bridging an unexpected blood loss until blood products become available for transfusion). Copyright (C) 2011 S. Karger AG, Base

Hele-Shaw beach creation by breaking waves: a mathematics-inspired experiment

Fundamentals of nonlinear wave-particle interactions are studied experimentally in a Hele-Shaw configuration with wave breaking and a dynamic bed. To design this configuration, we determine, mathematically, the gap width which allows inertial flows to survive the viscous damping due to the side walls. Damped wave sloshing experiments compared with simulations confirm that width-averaged potential-flow models with linear momentum damping are adequately capturing the large scale nonlinear wave motion. Subsequently, we show that the four types of wave breaking observed at real-world beaches also emerge on Hele-Shaw laboratory beaches, albeit in idealized forms. Finally, an experimental parameter study is undertaken to quantify the formation of quasi-steady beach morphologies due to nonlinear, breaking waves: berm or dune, beach and bar formation are all classified. Our research reveals that the Hele-Shaw beach configuration allows a wealth of experimental and modelling extensions, including benchmarking of forecast models used in the coastal engineering practice, especially for shingle beaches

A global method for coupling transport with chemistry in heterogeneous porous media

Modeling reactive transport in porous media, using a local chemical equilibrium assumption, leads to a system of advection-diffusion PDE's coupled with algebraic equations. When solving this coupled system, the algebraic equations have to be solved at each grid point for each chemical species and at each time step. This leads to a coupled non-linear system. In this paper a global solution approach that enables to keep the software codes for transport and chemistry distinct is proposed. The method applies the Newton-Krylov framework to the formulation for reactive transport used in operator splitting. The method is formulated in terms of total mobile and total fixed concentrations and uses the chemical solver as a black box, as it only requires that on be able to solve chemical equilibrium problems (and compute derivatives), without having to know the solution method. An additional advantage of the Newton-Krylov method is that the Jacobian is only needed as an operator in a Jacobian matrix times vector product. The proposed method is tested on the MoMaS reactive transport benchmark.Comment: Computational Geosciences (2009) http://www.springerlink.com/content/933p55085742m203/?p=db14bb8c399b49979ba8389a3cae1b0f&pi=1

A resting-state fMRI pattern of spinocerebellar ataxia type 3 and comparison with F-18-FDG PET

Spinocerebellar ataxia type 3 (SCA3) is a rare genetic neurodegenerative disease. The neurobiological basis of SCA3 is still poorly understood, and up until now resting-state fMRI (rs-fMRI) has not been used to study this disease. In the current study we investigated (multi-echo) rs-fMRI data from patients with genetically confirmed SCA3 (n = 17) and matched healthy subjects (n = 16). Using independent component analysis (ICA) and subsequent regression with bootstrap resampling, we identified a pattern of differences between patients and healthy subjects, which we coined the fMRI SCA3 related pattern (fSCA3-RP) comprising cerebellum, anterior striatum and various cortical regions. Individual fSCA3-RP scores were highly correlated with a previously published F-18-FDG PET pattern found in the same sample (rho = 0.78, P = 0.0003). Also, a high correlation was found with the Scale for Assessment and Rating of Ataxia scores (r = 0.63, P = 0.007). No correlations were found with neuropsychological test scores, nor with levels of grey matter atrophy. Compared with the F-18-FDG PET pattern, the fSCA3-RP included a more extensive contribution of the mediofrontal cortex, putatively representing changes in default network activity. This rs-fMRI identification of additional regions is proposed to reflect a consequence of the nature of the BOLD technique, enabling measurement of dynamic network activity, compared to the more static F-18-FDG PET methodology. Altogether, our findings shed new light on the neural substrate of SCA3, and encourage further validation of the fSCA3-RP to assess its potential contribution as imaging biomarker for future research and clinical use