Cerebral activations related to ballistic, stepwise interrupted and gradually modulated movements in parkinson patients

Patients with Parkinson's disease (PD) experience impaired initiation and inhibition of movements such as difficulty to start/stop walking. At single-joint level this is accompanied by reduced inhibition of antagonist muscle activity. While normal basal ganglia (BG) contributions to motor control include selecting appropriate muscles by inhibiting others, it is unclear how PD-related changes in BG function cause impaired movement initiation and inhibition at single-joint level. To further elucidate these changes we studied 4 right-hand movement tasks with fMRI, by dissociating activations related to abrupt movement initiation, inhibition and gradual movement modulation. Initiation and inhibition were inferred from ballistic and stepwise interrupted movement, respectively, while smooth wrist circumduction enabled the assessment of gradually modulated movement. Task-related activations were compared between PD patients (N = 12) and healthy subjects (N = 18). In healthy subjects, movement initiation was characterized by antero-ventral striatum, substantia nigra (SN) and premotor activations while inhibition was dominated by subthalamic nucleus (STN) and pallidal activations, in line with the known role of these areas in simple movement. Gradual movement mainly involved antero-dorsal putamen and pallidum. Compared to healthy subjects, patients showed reduced striatal/SN and increased pallidal activation for initiation, whereas for inhibition STN activation was reduced and striatal-thalamo-cortical activation increased. For gradual movement patients showed reduced pallidal and increased thalamo-cortical activation. We conclude that PD-related changes during movement initiation fit the (rather static) model of alterations in direct and indirect BG pathways. Reduced STN activation and regional cortical increased activation in PD during inhibition and gradual movement modulation are better explained by a dynamic model that also takes into account enhanced responsiveness to external stimuli in this disease and the effects of hyper-fluctuating cortical inputs to the striatum and STN in particular

Size constancy in bat biosonar?

Perception and encoding of object size is an important feature of sensory systems. In the visual system object size is encoded by the visual angle (visual aperture) on the retina, but the aperture depends on the distance of the object. As object distance is not unambiguously encoded in the visual system, higher computational mechanisms are needed. This phenomenon is termed "size constancy". It is assumed to reflect an automatic re-scaling of visual aperture with perceived object distance. Recently, it was found that in echolocating bats, the 'sonar aperture', i.e., the range of angles from which sound is reflected from an object back to the bat, is unambiguously perceived and neurally encoded. Moreover, it is well known that object distance is accurately perceived and explicitly encoded in bat sonar. Here, we addressed size constancy in bat biosonar, recruiting virtual-object techniques. Bats of the species Phyllostomus discolor learned to discriminate two simple virtual objects that only differed in sonar aperture. Upon successful discrimination, test trials were randomly interspersed using virtual objects that differed in both aperture and distance. It was tested whether the bats spontaneously assigned absolute width information to these objects by combining distance and aperture. The results showed that while the isolated perceptual cues encoding object width, aperture, and distance were all perceptually well resolved by the bats, the animals did not assign absolute width information to the test objects. This lack of sonar size constancy may result from the bats relying on different modalities to extract size information at different distances. Alternatively, it is conceivable that familiarity with a behaviorally relevant, conspicuous object is required for sonar size constancy, as it has been argued for visual size constancy. Based on the current data, it appears that size constancy is not necessarily an essential feature of sonar perception in bats

Long-term cognitive and behavioral consequences of neonatal encephalopathy following perinatal asphyxia: a review

Neonatal encephalopathy (NE) following perinatal asphyxia (PA) is considered an important cause of later neurodevelopmental impairment in infants born at term. This review discusses long-term consequences for general cognitive functioning, educational achievement, neuropsychological functioning and behavior. In all areas reviewed, the outcome of children with mild NE is consistently positive and the outcome of children with severe NE consistently negative. However, children with moderate NE form a more heterogeneous group with respect to outcome. On average, intelligence scores are below those of children with mild NE and age-matched peers, but within the normal range. With respect to educational achievement, difficulties have been found in the domains reading, spelling and arithmetic/mathematics. So far, studies of neuropsychological functioning have yielded ambiguous results in children with moderate NE. A few studies suggest elevated rates of hyperactivity in children with moderate NE and autism in children with moderate and severe NE. Conclusion: Behavioral monitoring is required for all children with NE. In addition, systematic, detailed neuropsychological examination is needed especially for children with moderate NE

Indirect two-sided relative ranking: a robust similarity measure for gene expression data

<p>Abstract</p> <p>Background</p> <p>There is a large amount of gene expression data that exists in the public domain. This data has been generated under a variety of experimental conditions. Unfortunately, these experimental variations have generally prevented researchers from accurately comparing and combining this wealth of data, which still hides many novel insights.</p> <p>Results</p> <p>In this paper we present a new method, which we refer to as indirect two-sided relative ranking, for comparing gene expression profiles that is robust to variations in experimental conditions. This method extends the current best approach, which is based on comparing the correlations of the up and down regulated genes, by introducing a comparison based on the correlations in rankings across the entire database. Because our method is robust to experimental variations, it allows a greater variety of gene expression data to be combined, which, as we show, leads to richer scientific discoveries.</p> <p>Conclusions</p> <p>We demonstrate the benefit of our proposed indirect method on several datasets. We first evaluate the ability of the indirect method to retrieve compounds with similar therapeutic effects across known experimental barriers, namely vehicle and batch effects, on two independent datasets (one private and one public). We show that our indirect method is able to significantly improve upon the previous state-of-the-art method with a substantial improvement in recall at rank 10 of 97.03% and 49.44%, on each dataset, respectively. Next, we demonstrate that our indirect method results in improved accuracy for classification in several additional datasets. These datasets demonstrate the use of our indirect method for classifying cancer subtypes, predicting drug sensitivity/resistance, and classifying (related) cell types. Even in the absence of a known (i.e., labeled) experimental barrier, the improvement of the indirect method in each of these datasets is statistically significant.</p

Do you see what I see? Identification of child protection concerns by hospital staff and general dental practitioners

Aim An exploration of the threshold that dentists, doctors and nurses recognise for dental and child protection (CP) actions in sample clinical cases, and any differences between these professional groups. Method We present a cross-sectional survey of dentists, doctors and nurses (50 each), who regularly examine children, utilised five fictitious vignettes, combining an oral examination image and clinical history reflecting dental and CP issues. Demographics were collected, and each participant gave their likely action for the cases presented. Results Dentists were significantly better at answering the dental element than the doctors and nurses, (P <0.0001) with no significant difference between these two; only 8% of the latter had undergone any training in assessment of dental health. Although 90.6% of all professionals had undergone CP training, dentists were significantly less accurate at identifying the CP component than doctors and nurses, (P <0.0001) between whom there were no significant differences. Those with higher levels of CP training were most accurate at identifying correct CP actions. Conclusions CP training is effective at improving recognition of child maltreatment, although there remains a worrying lack of knowledge about thresholds for action among dentists. Doctors and nurses have minimal training in, or knowledge of, dental health in children, thus precluding appropriate onward referrals

Using principal component analysis to develop a single-parameter screening tool for metabolic syndrome

Abstract Background Metabolic syndrome (MS) is an important current public health problem faced worldwide. To prevent an "epidemic" of this syndrome, it is important to develop an easy single-parameter screening technique (such as waist circumference (WC) determination recommended by the International Diabetes Federation). Previous studies proved that age is a chief factor corresponding to central obesity. We intended to present a new index based on the linear combination of body mass index, and age, which could enhance the area under the receiver operating characteristic curves (AUCs) for assessing the risk of MS. Methods The labour law of the Association of Labor Standard Law, Taiwan, states that employers and employees are respectively obligated to offer and receive routine health examination periodically. Secondary data analysis and subject's biomarkers among five high-tech factories were used in this study between 2007 and 2008 in northern Taiwan. The subjects included 4712 males and 4196 females. The first principal component score (FPCS) and equal-weighted average (EWA) were determined by statistical analysis. Results Most of the metabolic and clinical characteristics were significantly higher in males than in females, except high-density lipoprotein cholesterol level. The older group (>45 years) had significantly lower values for height and high-density lipoprotein cholesterol level than the younger group. The AUCs of FPCS and EWA were significantly larger than those of WC and waist-to-height ratio. The low specificities of EWA and FPCS were compensated for by their substantially high sensitivities. FPCS ≥ 0.914 (15.4%) and EWA ≥ 8.8 (6.3%) were found to be the most prevalent cut off points in males and females, respectively. Conclusions The Bureau of Health Promotion, Department of Health, Taiwan, had recommended the use of WC ≥ 90 cm for males and ≥ 80 cm for females as singular criteria for the determination of central obesity instead of multiple parameters. The present investigation suggests that FPCS or EWA is a good predictor of MS among the Taiwanese. However, the use of FPCS is not computationally feasible in practice. Therefore, we suggest that EWA be used in clinical practice as a simple parameter for the identification of those at risk of MS.</p

Impairment of Gradual Muscle Adjustment during Wrist Circumduction in Parkinson's Disease

Purposeful movements are attained by gradually adjusted activity of opposite muscles, or synergists. This requires a motor system that adequately modulates initiation and inhibition of movement and selectively activates the appropriate muscles. In patients with Parkinson's disease (PD) initiation and inhibition of movements are impaired which may manifest itself in e.g. difficulty to start and stop walking. At single-joint level, impaired movement initiation is further accompanied by insufficient inhibition of antagonist muscle activity. As the motor symptoms in PD primarily result from cerebral dysfunction, quantitative investigation of gradually adjusted muscle activity during execution of purposeful movement is a first step to gain more insight in the link between impaired modulation of initiation and inhibition at the levels of (i) cerebrally coded task performance and (ii) final execution by the musculoskeletal system. To that end, the present study investigated changes in gradual adjustment of muscle synergists using a manipulandum that enabled standardized smooth movement by continuous wrist circumduction. Differences between PD patients (N = 15, off-medication) and healthy subjects (N = 16) concerning the relation between muscle activity and movement performance in these groups were assessed using kinematic and electromyographic (EMG) recordings. The variability in the extent to which a particular muscle was active during wrist circumduction – defined as muscle activity differentiation - was quantified by EMG. We demonstrated that more differentiated muscle activity indeed correlated positively with improved movement performance, i.e. higher movement speed and increased smoothness of movement. Additionally, patients employed a less differentiated muscle activity pattern than healthy subjects. These specific changes during wrist circumduction imply that patients have a decreased ability to gradually adjust muscles causing a decline in movement performance. We propose that less differentiated muscle use in PD patients reflects impaired control of modulated initiation and inhibition due to decreased ability to selectively and jointly activate muscles

A study of the diagnostic accuracy of the PHQ-9 in primary care elderly

<p>Abstract</p> <p>Background</p> <p>The diagnostic accuracy of the Patient Health Questionnaire-9 (PHQ-9) for assessment of depression in elderly persons in primary care settings in the United States has not been previously addressed. Thus, the purpose of this study was to evaluate the test performance of the PHQ-9 for detecting major and minor depression in elderly patients in primary care.</p> <p>Methods</p> <p>A prospective study of diagnostic accuracy was conducted in two primary care, university-based clinics in the Pacific Northwest of the United States. Seventy-one patients aged 65 years or older participated; all completed the PHQ-9 and the 15-item Geriatric Depression Scale (GDS) and underwent the Structured Clinical Interview for Depression (SCID). Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve, and likelihood ratios (LRs) were calculated for the PHQ-9, the PHQ-2, and the 15-item GDS for major depression alone and the combination of major plus minor depression.</p> <p>Results</p> <p>Two thirds of participants were female, with a mean age of 78 and two chronic health conditions. Twelve percent met SCID criteria for major depression and 13% minor depression. The PHQ-9 had an area under the curve (AUC) of 0.87 (95% confidence interval [CI], 0.74-1.00) for major depression, while the PHQ-2 and the 15-item GDS each had an AUC of 0.81 (95% CI for PHQ-2, 0.64-0.98, and for 15-item GDS, 0.70-0.91; <it>P </it>= 0.551). For major and minor depression combined, the AUC for the PHQ-9 was 0.85 (95% CI, 0.73-0.96), for the PHQ-2, 0.80 (95% CI, 0.68-0.93), and for the 15-item GDS, 0.71 (95% CI, 0.55-0.87; <it>P </it>= 0.187).</p> <p>Conclusions</p> <p>Based on AUC values, the PHQ-9 performs comparably to the PHQ-2 and the 15-item GDS in identifying depression among primary care elderly.</p

Sensory substitution information informs locomotor adjustments when walking through apertures

The study assessed the ability of the central nervous system (CNS) to use echoic information from sensory substitution devices (SSDs) to rotate the shoulders and safely pass through apertures of different width. Ten visually normal participants performed this task with full vision, or blindfolded using an SSD to obtain information regarding the width of an aperture created by two parallel panels. Two SSDs were tested. Participants passed through apertures of +0%, +18%, +35%, and +70% of measured body width. Kinematic indices recorded movement time, shoulder rotation, average walking velocity across the trial, peak walking velocities before crossing, after crossing and throughout a whole trial. Analyses showed participants used SSD information to regulate shoulder rotation, with greater rotation associated with narrower apertures. Rotations made using an SSD were greater compared to vision, movement times were longer, average walking velocity lower and peak velocities before crossing, after crossing and throughout the whole trial were smaller, suggesting greater caution. Collisions sometimes occurred using an SSD but not using vision, indicating that substituted information did not always result in accurate shoulder rotation judgements. No differences were found between the two SSDs. The data suggest that spatial information, provided by sensory substitution, allows the relative position of aperture panels to be internally represented, enabling the CNS to modify shoulder rotation according to aperture width. Increased buffer space indicated by greater rotations (up to approximately 35% for apertures of +18% of body width), suggests that spatial representations are not as accurate as offered by full vision

Considerations for determining optimal mouse caging density

At the 2006 National Meeting of the American Association of Laboratory Animal Science, a panel discussed the question of what constitutes optimal or acceptable housing density for mice. Though there is a consensus that present guidelines are somewhat arbitrarily defined, scientific research has not yet been able to provide clear recommendations for amending them. Speakers explored the many factors that influence decisions on mouse housing, including regulatory requirements, scientific data and their interpretation, financial considerations and ethical concerns. The panel largely agreed that animal well-being should be the measure of interest in evaluating housing density and that well-being includes not only physical health, but also animals\u27 behavior, productivity and preference