Toward a “treadmill test” for cognition: Improved prediction of general cognitive ability from the task activated brain

General cognitive ability (GCA) refers to a trait‐like ability that contributes to performance across diverse cognitive tasks. Identifying brain‐based markers of GCA has been a longstanding goal of cognitive and clinical neuroscience. Recently, predictive modeling methods have emerged that build whole‐brain, distributed neural signatures for phenotypes of interest. In this study, we employ a predictive modeling approach to predict GCA based on fMRI task activation patterns during the N‐back working memory task as well as six other tasks in the Human Connectome Project dataset (n = 967), encompassing 15 task contrasts in total. We found tasks are a highly effective basis for prediction of GCA: The 2‐back versus 0‐back contrast achieved a 0.50 correlation with GCA scores in 10‐fold cross‐validation, and 13 out of 15 task contrasts afforded statistically significant prediction of GCA. Additionally, we found that task contrasts that produce greater frontoparietal activation and default mode network deactivation—a brain activation pattern associated with executive processing and higher cognitive demand—are more effective in the prediction of GCA. These results suggest a picture analogous to treadmill testing for cardiac function: Placing the brain in a more cognitively demanding task state significantly improves brain‐based prediction of GCA.     

Developing fMRI protocol for clinical use Comparison of 6 Arabic paradigms for brain language mapping in native Arabic speakers

Objectives:To assess a baseline assessment using developed functional magnetic resonance imaging (fMRI) language paradigms for Arabic-speakers.Methods:24-healthy right-handed volunteers scanned on a 3.0 Tesla MRI machine. For fMRI, a BOLD-sensitive sequence used to measure signals over time across 6 language paradigms: rhyming (RH), semantic category generations (SCG), silent word generation (SWG), verb generation picture (VGp), verb generation word (VGw), and verb generation audio (VGa). fMRI data was analyzed using FMRIB Software Library (FSL).Results:We found that VGa, SWG, VGw and VGp robustly activated language-related regions in the dominant hemisphere. RH and SCG failed to adequately define these activation regions but this may be related to the study’s preliminary nature and limitations. After assessment of their validity, considerable activation of the inferior frontal gyrus during VGa, SWG, VGw and VGp suggests that these paradigms have the potential for localizing of Broca’s area in native Arabic speakers.Conclusion:Set of well adapted, and evidence-based, fMRI paradigms were established for Arabic-speakers to enable accurate and sufficient localization and lateralization of the language area. After validation, these paradigms may provide sequences for accurate localization of brain language areas, and could be used as a presurgical evaluation tool.

Functional magnetic resonance imaging (fMRI) allows precise, and non-invasive, localization and lateralization of brain functions. Clinically, these techniques have considerable success, and hold great potential in the management of a variety of neurological disorders. One of the most promising clinical applications of fMRI is presurgical linguistic mapping.1-5 The 3 classical language areas that are involved in language production and processing are Broca’s and Wernicke’s areas, and angular gyrus. Wernicke’s area can be described as a receptive region, for processing and integrating auditory sensory information, while Broca’s area can be described as a productive region, for making vocal signals, and meaningful words or sentences. The latter includes pars opercularis and triangularis. The angular gyrus area is particularly involved in reading and transitioning between written and spoken forms of language. Injury to language regions produces noticeable clinical deficits, and the location of these regions may become difficult to assess without advanced anatomical imaging such as fMRI. Internationally, fMRI replaces the more invasive Wada test (also known as the intracarotid sodium amobarbital procedure) in lateralizing language and memory at some centers.6,7Language is a highly complex system that markedly varies across individuals. Patients native language affects brain activation responses during fMRI scans.8-13 As such, language paradigms for presurgical fMRI mapping should be developed and validated using native language paradigms. Language dominance of the left cerebral hemisphere has been well researched and established, but native language and social factors were also reported to play a key role in cortical association of verbal processing.8,14-16Although language localization using fMRI has been routinely used in western countries, and more recently in an Arabic country,17 studies clearly demonstrated that different cultures may process language in different manners, using different brain mechanisms.8,14-16 Existing language paradigms, created for non-Arabic speaking patients, require major modifications before applying them in examining native Arabic speakers.17Language lateralization is another broadly used clinical application of fMRI. Concordance with Wada test has long been demonstrated and validated in the literature using paradigms with various tasks such as verbal fluency, comprehension, and semantic judgment .18-21 These have shown that concordance with Wada test can reach 90% in temporal lobe epilepsy, especially in left-dominant patients. A slightly lower concordance was achieved in right-dominant patients. Although fMRI language lateralization works well for patients with typical language dominance, clinicians need to be careful when interpreting results of patients with atypical language representation.22Semitic languages such as Arabic differ from other languages in many aspects, including orthography (including diacritics), phonology, and syntax. Therefore, significant research in developing and validating language paradigms for Arabic is required. To our knowledge, very few studies in this domain have been carried out.17,23 One developed several language and memory paradigms in neurological patients, while emphasizing consideration for educational and cultural adjustments,17 and the other examined neuronal correlates of diacritics (vs. lack of thereof) in 11 healthy men.23We aim to establish tasks adapted to the Arabic language, that also reliably activate Broca’s and Wernicke’s areas in a relatively short scanning time. This study is a baseline assessment using 6 developed fMRI language paradigms for Arabic-speaking presurgical candidates. The desired outcome of this work is to create a set of Arabic language localization protocols, along with standard operating procedures.     

Chemical priming for spinal cord injury: a review of the literature. Part I��factors involved

Introduction  

There are significant differences between the propensity of neural regeneration between the central and peripheral nervous systems.     

Chemical priming for spinal cord injury: a review of the literature part II��potential therapeutics

Introduction  

Spinal cord injury is a complex cascade of reactions secondary to the initial mechanical trauma that puts into action the innate properties of the injured cells, the circulatory, inflammatory, and chemical status around them, into a non-permissive and destructive environment for neuronal function and regeneration. Priming means putting a cell, in a state of “arousal” towards better function. Priming can be mechanical as trauma is known to enhance activity in cells.     

On skewness and kurtosis of econometric estimators

Summary We derive the approximate results for two standardized measures of deviation from normality, namely, the skewness and excess kurtosis coefficients, for a class of econometric estimators. The results are built on a stochastic expansion of the moment condition used to identify the econometric estimator. The approximate results can be used not only to study the finite sample behaviour of a particular estimator, but also to compare the finite sample properties of two asymptotically equivalent estimators. We apply the approximate results to the spatial autoregressive model and find that our results approximate the non‐normal behaviours of the maximum likelihood estimator reasonably well. However, when the weights matrix becomes denser, the finite sample distribution of the maximum likelihood estimator departs more severely from normality and our results provide less accurate approximation.     

Varied manifestations of Rosai-Dorfman disease and its management — a case report and review of literature

Rosai Dorfman disease or sinus histiocytosis is a rare, idiopathic, benign and self-limiting histiocytic proliferative disorder, usually seen in younger patients. It most commonly involves the cervical lymph nodes, with a predominant infiltration of sinusoidal histiocytes and classically presents with massive cervical lymhadenopathy. Extranodal disease occurs in about 43% of cases and produces different signs and symptoms depending upon its location. We report a case of this disorder in 22-year-old male with initial isolated involvement of bilateral nasal cavity and paranasal sinuses with subsequent involvement of cervical lymph nodes and skin. The clinical presentation, histologic characterstics, radiographic findings and treatment of the disease are discussed.     

Effect of antibiotic therapy on the density of vancomycin-resistant enterococci in the stool of colonized patients

BACKGROUND: Colonization and infection with vancomycin-resistant enterococci have been associated with exposure to antibiotics that are active against anaerobes. In mice that have intestinal colonization with vancomycin-resistant enterococci, these agents promote high-density colonization, whereas antibiotics with minimal antianaerobic activity do not. METHODS: We conducted a seven-month prospective study of 51 patients who were colonized with vancomycin-resistant enterococci, as evidenced by the presence of the bacteria in stool. We examined the density of vancomycin-resistant enterococci in stool during and after therapy with antibiotic regimens and compared the effect on this density of antianaerobic agents and agents with minimal antianaerobic activity. In a subgroup of 10 patients, cultures of environmental specimens (e.g., from bedding and clothing) were obtained. RESULTS: During treatment with 40 of 42 antianaerobic-antibiotic regimens (95 percent), high-density colonization with vancomycin-resistant enterococci was maintained (mean [+/-SD] number of organisms, 7.8+/-1.5 log per gram of stool). The density of colonization decreased after these regimens were discontinued. Among patients who had not received antianaerobic antibiotics for at least one week, 10 of 13 patients who began such regimens had an increase in the number of organisms of more than 1.0 log per gram (mean increase, 2.2 log per gram), whereas among 10 patients who began regimens of antibiotics with minimal antianaerobic activity, there was a mean decrease in the number of enterococci of 0.6 log per gram (P=0.006 for the difference between groups). When the density of vancomycin-resistant enterococci in stool was at least 4 log per gram, 10 of 12 sets of cultures of environmental specimens had at least one positive sample, as compared with 1 of 9 sets from patients with a mean number of organisms in stool of less than 4 log per gram (P=0.002). CONCLUSIONS: For patients with vancomycin-resistant enterococci in stool, treatment with antianaerobic antibiotics promotes high-density colonization. Limiting the use of such agents in these patients may help decrease the spread of vancomycin-resistant enterococci.     

Hypoglycaemia in childhood diabetes. II. Effect of subcutaneous or intramuscular injection of different doses of glucagon

Hypoglycaemia (blood glucose 1.3-2.5 mmol/l) was induced in thirty diabetic children by reduction of their morning meal. Glucagon, 10 or 20 micrograms/kg was then given by intramuscular or subcutaneous injection. Ten min later, all signs of hypoglycaemia had disappeared and blood glucose concentrations increased by 0.7-3.3 mmol/l. Glucagon plasma concentrations at glucose nadir were low, 23 +/- 8 pmol/l, rose to 300 +/- 42 ten min after the injection and reached peak values after another ten min. Later, a slow decrease was noted. No significant difference of blood glucose or plasma glucagon concentrations were found after subcutaneous or intramuscular injections of 20 micrograms/kg. After 10 micrograms/kg, slightly lower increase of blood glucose was seen, but the clinical effect was equally good. Nausea occurred in four children given 20 micrograms/kg. The rise of blood glucose did not correlate to the peak glucagon concentration obtained after the injection but showed significant correlations to the lowest glucose concentration and, inversely, to the concentration of free insulin in blood at glucose nadir. It is concluded that glucagon injections are effective in hypoglycaemia in insulin-treated diabetic children and that the injection of 10-20 micrograms/kg gives long-standing supraphysiological concentrations which make repeated injections unnecessary.     

The influence of formulation and manufacturing process on the photostability of tablets

The formulation and the manufacturing process can significantly influence the photostability of tablets. Investigations of various formulation and manufacturing parameters were done with tablets containing nifedipine and molsidomine as highly light sensitive drugs. The effect of relevant formulation factors are stated. Whereas the particle size of the drug substance and the choice of the lubricant had no effect, the drug content, the compression diluent and geometric alterations significantly affected the photoinstability. Depending on the formulation drug losses varied between 30 and 55% after 12 h irradiation in a light testing cabinet (Suntest CPS+). Manufacturing parameters like compression force and direct compression versus granulation showed less serious influences. Nevertheless, photostability changes up to 10% were registered.