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An integrative MEG-fMRI study of the primary somatosensory cortex using cross-modal correspondence analysis.

We develop a novel approach of cross-modal correspondence analysis (CMCA) to address whether brain activities observed in magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) represent a common neuronal subpopulation, and if so, which frequency band obtained by MEG best fits the common brain areas. Fourteen adults were investigated by whole-head MEG using a single equivalent current dipole (ECD) and synthetic aperture magnetometry (SAM) approaches and by fMRI at 1.5 T using linear time-invariant modeling to generate statistical maps. The same somatosensory stimulus sequences consisting of tactile impulses to the right sided: digit 1, digit 4 and lower lip were used in both neuroimaging modalities. To evaluate the reproducibility of MEG and fMRI results, one subject was measured repeatedly. Despite different MEG dipole locations and locations of maximum activation in SAM and fMRI, CMCA revealed a common subpopulation of the primary somatosensory cortex, which displays a clear homuncular organization. MEG activity in the frequency range between 30 and 60 Hz, followed by the ranges of 20-30 and 60-100 Hz, explained best the defined subrepresentation given by both MEG and fMRI. These findings have important implications for improving and understanding of the biophysics underlying both neuroimaging techniques, and for determining the best strategy to combine MEG and fMRI data to study the spatiotemporal nature of brain activity.

Adult↗

Neural correlates of feigned memory impairment.

While initial neuroimaging studies have provisionally identified activation in the prefrontal (including the anterior cingulate) and parietal regions during lying, the robustness of this neuroanatomical pattern of activation across forms of stimuli, genders, and mother tongues remains to be demonstrated. In this paper we report the results of three studies designed to test the reproducibility of the brain activation previously observed during feigned memory impairment. A total of twenty-nine right-handed participants, divided into three cohorts, participated in three different studies of feigned memory impairment. Findings indicate that bilateral activation of prefrontal and parietal regions was invariant across stimulus types, genders, and mother tongues, suggesting the general importance of these regions during malingering and possibly deception in general. In conjunction with earlier imaging findings, these three studies suggest that the prefrontal parietal network provides a robust neuroanatomical foundation upon which future dissimulation research may build.

Adult↗

On the influence of soft tissue coverage in the determination of bone kinematics using skin markers.

Accurate measurement of underlying bone positions is important for the understanding of normal movement and function, as well as for addressing clinical musculoskeletal or post-injury problems. Non-invasive measurement techniques are limited by the analysis technique and movement of peripheral soft tissues that can introduce significant measurement errors in reproducing the kinematics of the underlying bones when using external skin markers. Reflective markers, skeletally mounted to the right hind limb of three Merino-mix sheep were measured simultaneously with markers attached to the skin of each segment, during repetitions of gait trials. The movement of the skin markers relative to the underlying bone positions was then assessed using the Point Cluster Technique (PCT), raw averaging and the Optimal Common Shape Technique (OCST), a new approach presented in this manuscript. Errors in the position of the proximal joint centre, predicted from the corresponding skin markers, were shown to be phasic and strongly associated with the amount soft tissue coverage, averaging 8.5 mm for the femur, 2.8 for the tibia and 2.0 for the metatarsus. Although the results show a better prediction of bone kinematics associated with the Optimal Common Shape Technique, these errors were large for all three assessment techniques and much greater than the differences between the various techniques. Whilst individual markers moved up to 4 mm from the optimal marker set configuration, average peak errors of up to 16, 5 and 3 mm (hip, knee and tibio-metatarsal joints respectively) were observed, suggesting that a large amount of kinematic noise is produced from the synchronous shifting of marker sets, potentially as a result of underlying muscle firing and the inertial effects of heel impact. Current techniques are therefore limited in their ability to determine the kinematics of underlying bones based on skin markers, particularly in segments with more pronounced soft tissue coverage.

Animals↗

Femoral neck strength of mouse in two loading configurations: method evaluation and fracture characteristics.

We evaluated the mechanical strength of murine femoral neck in two loading configurations. The mechanical strength of the left femora of 25 male mice (weight 39 +/- 4 g) were measured in an axial configuration simulating one-legged stance in a human, and the right femora were tested in a configuration simulating a fall to the lateral side, on the trochanter. The reproducibility of the mechanical testing was 1.6% in the axial configuration and 3.7% in the fall configuration. The femoral neck was slightly stronger in the fall configuration. Typically, a load in the fall direction associated with a basicervical fracture, while axial loading resulted in both mid- and basicervical fractures. The linear bivariate correlation coefficient between the mechanical strengths in the two loading configurations was 0.83. Total bone mineral content (BMC), cortical bone mineral content (CtBMC), volumetric cortical bone mineral density (vCtBMD), and cross-sectional cortical area (CSA), measured at the femoral neck by peripheral quantitative computed tomography (pQCT), had a significant relationship with the femoral neck strength in the axial configuration. The coefficient of variation of the pQCT measurements was 9.1, 5.5, 2.3 and 5.5% for BMC, CtBMC, vCtBMD and CSA, respectively. We conclude that the precision of pQCT is moderate in evaluating the femoral neck of the mouse, and vCtBMD is the most reproducible parameter. The mechanical strength of the murine femoral neck can be measured with high precision by the two mechanical testing configurations presented here.

Accidental Falls↗

Right hemispheric self-awareness: a critical assessment.

In this commentary I evaluate the claim made by that since self-recognition results from right hemispheric activity, self-awareness too is likely to be produced by the activity of the same hemisphere. This reasoning is based on the assumption that self-recognition represents a valid operationalization of self-awareness; I present two views that challenge this rationale. Keenan et al. also support their claim with published evidence relating brain activity and self-awareness; I closely examine their analysis of one specific review of literature and conclude that it appears to be biased. Finally, recent research suggests that inner speech (which is associated with left hemispheric activity) is linked to self-awareness-an observation that further casts doubt on the existence of a right hemispheric self-awareness.

Awareness↗

Relationship of gender, body mass index, and axial length with central retinal thickness using optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) acquires cross-sectional retinal images with high resolution using low-coherence interferometry. Few studies have studied the effect of demographic data and ocular parameters that may affect central retinal thickness. In this study, these factors were used as parameters to analyse if any significant relationship exists with central retinal thickness. METHODS: Volunteers with a best-corrected visual acuity of 6/12 or better and no evidence of ocular abnormalities or interventions were recruited from October 2001 to March 2003. Body mass index (BMI), autorefraction, and keratometry recordings were measured, followed by applanation tonometry and A-scan ultrasonography. The central retinal thickness of the right eye was analysed using a scan length of 3 cm. Another 25 eyes were selected for interobserver reproducibility. RESULTS: In all, 117 normal subjects (60 male and 57 female subjects) were recruited. The mean thickness of the central retina with a diameter of 1 mm was 203+/-23 microm for male and 189+/-20 microm for female subjects. Age, intraocular pressure, and keratometric readings were not significantly correlated with central retinal thickness. Using multiple regression, gender, BMI, axial length, and signal-to-noise ratio (P<0.05) were significantly associated with the central retinal thickness. The intraclass correlation coefficient was 0.98 for interobserver reproducibility. CONCLUSION: OCT has a high interobserver reproducibility. The male gender, larger BMI, and longer axial length are associated with a significantly thicker central retina and these parameters should be considered for assessing retinal thickening and baseline comparisons in future studies.

Adolescent↗

Role of peptidase and cyclooxygenase inhibitors in the guinea-pig bronchial response to the synthetic endothelin ET(B) agonist IRL 1620 and antagonist BQ-788.

In isolated guinea-pig bronchial preparations the selective endothelin ETB agonist, IRL 1620 caused a concentration-dependent contraction. The pD2 value (7.16 +/- 0.09, n = 6) was significantly increased in the presence of peptidase inhibitors (thiorfan 1 microM, captopril 1 microM, bestatin 1 microM) (pD2 = 7.75 +/- 0.09, n = 6). Indomethacin (5 microM) did not appear to influence the ETB-agonist pD2 value (6.92 + 0.11, n = 6) but potentiated its maximal response significantly (67.23 +/- 4.81% vs. 53.37 +/- 4.80%). The concentration-response curve for the contractile response to IRL 1620 (pD2=7.83 +/- 0.01, n=16); was reproducible, although not completely, since the second curve to this selective ETB agonist was shifted significantly to the right (pD2 = 7.34 +/- 0.09, n = 16) and a decrease in the maximal response was observed (20.0 +/- 2.0%). BQ 788, a selective antagonist for ETB receptors, employed in concentrations ranging from 1.5 to 150 nM, caused a dose-dependent shift to the right of the concentration-response curve to IRL 1620, with a pIC50 value of 8.11 +/- 0.03; this action was not influenced by adding enzyme inhibitors (pIC50 = 8.17 +/- 0.29). Our data show that IRL 1620 undergoes a hydrolytic metabolism in guinea-pig bronchial preparations, which could influence the calculation of the pD2. Pretreatment of the tissue with peptidase inhibitors and indomethacin is consequently significant in the evaluation of IRL 1620 activity, while it does not influence the action of the antagonist, BQ 788.

Animals↗

Operative contractility: a functional concept of the inotropic state.

1. Initial unsuccessful attempts to evaluate ventricular function in terms of the 'heart as a pump' led to focusing on the 'heart as a muscle' and to the concept of myocardial contractility. However, no clinically ideal index exists to assess the contractile state. The aim of the present study was to develop a mathematical model to assess cardiac contractility. 2. A tri-axial system was conceived for preload (PL), afterload (AL) and contractility, where stroke volume (SV) was represented as the volume of the tetrahedron. Based on this model, 'operative' contractility ('OperCon') was calculated from the readily measured values of PL, AL and SV. The model was tested retrospectively under a variety of different experimental and clinical conditions, in 71 studies in humans and 29 studies in dogs. A prospective echocardiographic study was performed in 143 consecutive subjects to evaluate the ability of the model to assess contractility when SV and PL were measured volumetrically (mL) or dimensionally (cm). 3. With inotropic interventions, OperCon changes were comparable to those of ejection fraction (EF), velocity of shortening (Vcf) and dP/dt-max. Only with positive inotropic interventions did elastance (Ees) show significantly larger changes. With load manipulations, OperCon showed significantly smaller changes than EF and Ees and comparable changes to Vcf and dP/dt-max. Values of OperCon were similar when AL was represented by systolic blood pressure or wall stress and when volumetric or dimensional values were used. 4. Operative contractility is a reliable, simple and versatile method to assess cardiac contractility.

Adult↗

Clinical morphology of sodium lauryl sulfate (SLS) and nonanoic acid (NAA) irritant patch test reactions at 48 h and 96 h in 152 subjects.

In this study of 152 women, comparison of patch test responses between 2 irritants over 96 h at 2 symmetrical anatomical sites is studied. 2 irritants, each at 4 different concentrations (nonanoic acid (NAA) 80%, 40%, 20%, 10%; sodium lauryl sulfate (SLS) 3%, 2%, 1% and 0.5%) and using propan-1ol and 'water for injection' as the respective controls, were placed as 15 microl aliquots, soaked onto filter paper discs in Finn Chambers, on the volunteer's left and right lower back. The patches were removed at 47, and read at 48 and 96 h. Irritant reactions were evaluated for erythema and surface changes by degree and area affected. Statistical analysis of the results showed that erythema decreased with time for all concentrations of NAA, and at higher concentrations for SLS. Surface changes increased with time for SLS and at higher concentrations of NAA. There was no statistically significant difference comparing left and right sides. Traditionally in patch testing, reactions which fade after 48 h have been regarded as irritant rather than allergic. This study refutes that assumption. Data from our left to right comparisons, made in the same individuals at the same time, show that irritant reactions may be more reproducible than previously appreciated.

Adolescent↗

The natural discharges of Purkinje cells in paravermal regions of lobules V and VI of the monkey's cerebellum.

1. Conscious monkeys were trained with food rewards to perform movement tasks with the left hand and to accept manipulation of the joints and muscles and natural non-noxious stimulation of the skin of both forelimbs.2. Recordings were made from 230 Purkinje cells situated in the paravermal region of lobules V and VI or immediately adjacent folia of the left cerebellum in a region from 2 to 7 mm from the mid line. These neurones were all in a zone which was demonstrated to receive inputs from the ipsilateral hand and which is known to receive projections, via the pontine nuclei from the ;arm area' of motor cortex in the right hemisphere.3. Modulation of the natural activity of 182 of these 230 Purkinje cells (79%) occurred in a reproducible manner in temporal association, each with a particular phase of the self-paced movement tasks performed by the animal using the ipsilateral arm and hand. The patterns of modulation of Purkinje cell firing in this limited zone of cerebellar cortex could be classified into one of four groups, and each cell's discharge was associated with a particular aspect of movement such as general arm flexion, shoulder retraction, elbow extension or elbow flexion whenever it occurred.4. The cells were spontaneously active at rest. Most commonly, marked accelerations of the discharge were related to one direction of the particular aspect of movement and a reduction of activity or even total silence accompanied movement in the opposite direction.5. Variation of the amount of discharge demonstrated during a movement performance with which this discharge was characteristically associated could be related to the range of the movement or its duration, more activity being characteristic of more prolonged movement performance through larger angles of joint displacement.6. Both simple spikes and complex spikes of some cells showed characteristic modulation of their activity during the monkey's self-initiated movements. Cells whose simple spikes did not change in frequency during the movement task, also showed no modification of complex spike discharge.7. Of the 182 neurones whose discharges changed during active movement performance, 105 (roughly 60%) were demonstrated to be in receipt of an input from peripheral receptors in the hand which could be activated by brisk tapping of the skin or brushing of hairs. In contrast, none of the Purkinje cells whose discharges were unchanged during arm movements could be demonstrated to receive such an input.8. Movement of joints through their full range and prodding of muscles were completely ineffective stimuli for causing changes in Purkinje cell firing in this zone of the cerebellar cortex while the animal was passive and relaxed. Imposed perturbations of movement performance injected unexpectedly during the execution of a movement task were also ineffective in modifying the discharge of these Purkinje cells in relation to the task.

Action Potentials↗

Structure of the SAD mutation and the location of control sites at silent mating type genes in Saccharomyces cerevisiae.

The SAD mutation, an extra mating type cassette, has been shown to arise from an unequal mitotic crossover between the MAT and HMR loci, resulting in the formation of a hybrid cassette and a duplication of the MAT-HMR interval. The SAD cassette contains the "a" information and left-hand flanking regions from the parental HMRa cassette and the right-hand flanking sequences of the parental MAT cassette. This arrangement of flanking sequences causes a leaky but reproducible mating phenotype correlated with a low-level expression of the cassette as measured by RNA blotting. This weak expression is attributed to the loss of one flanking control site normally present at the silent HM storage loci.

Alleles↗

Failure of propranolol to improve exercise tolerance in patients with mitral stenosis in sinus rhythm.

Propranolol reduces left atrial pressure at rest and during exercise in patients with mitral stenosis by lowering cardiac output and heart rate. Ten patients (aged 19-56) with moderate to severe isolated mitral stenosis were studied to determine whether propranolol increased their exercise tolerance. All were in sinus rhythm and free of left or right ventricular failure. Patients were trained in an individually graded bicycle or treadmill exercise protocol that provoked a reproducible degree of near maximal dyspnoea during the second three minute stage of exercise. Propranolol (80 mg or 120 mg) or matching placebo in two or three divided daily doses was given for one week in random double blind fashion. Exercise testing and questioning about subjective clinical response were carried out at the end of each week by an investigator who was unaware of the patient's heart rate. During propranolol treatment the heart rate was 19 beats/minute slower at rest and 38 beats/minute slower at peak exercise, but there was no change in mean exercise time to dyspnoea (274 s during propranolol vs 283 s during placebo). Four patients felt worse during the propranolol week, one patient felt better during the propranolol week, and five patients felt no difference between the two weeks. Propranolol did not improve objective or subjective exercise tolerance in patients with isolated mitral stenosis in sinus rhythm.

Adult↗

Reliability and validity of bilateral thigh and foot accelerometry measures of walking in healthy and hemiparetic subjects.

OBJECTIVE: Measures of walking ability in large clinical trials are usually limited to a timed short-distance walk and the distance walked in a fixed time. A new integrated system of 5 accelerometers was tested for reliability and compared to a footswitch system to determine if the accelerometers offered a practical option for the acquisition of spatiotemporal gait parameters. METHODS: Leg accelerations and decelerations were defined in relation to simultaneous kinematic and electromyographic data acquired from a healthy subject. Eight healthy adults and 6 independent ambulators with hemiparetic stroke walked 15 m at 2 different speeds wearing both the accelerometers and footswitches. Twelve healthy subjects walked at 5 different speeds repeated 3 times on each of 2 days wearing the accelerometers. Walking speed, cadence, stride length, and single- and double-limb support, swing, and stance times were calculated. RESULTS: No differences (t test, P > 0.2) were found between footswitch and accelerometer variables when comparing all left or right legs in healthy subjects and all paretic or unaffected legs in stroke subjects. A 2-way nested ANOVA model (speed, left and right legs, trial, and session) with the accelerometers at walking speeds from 0.5 to 1.8 m/s revealed high reproducibility of all measures. CONCLUSIONS: The accelerometry system provided reliable and valid spatiotemporal measures of gait for the upper range of speeds likely to be targeted for rehabilitation interventions in ambulatory subjects.

Acceleration↗

Antitachycardia burst pacing for pleomorphic reentrant ventricular tachycardias associated with non-coronary artery diseases: a morphology specific programming for ventricular tachycardias.

To study the role of antitachycardia burst pacing in patients with reentrant pleomorphic ventricular tachycardia (VT) associated with non-coronary artery diseases, the efficacy of antitachycardia pacing and appropriate antitachycardia pacing cycle length were evaluated in each pleomorphic VT morphology of seven patients. Seven patients were included in this study. Clinically documented pleomorphic VTs were reproduced in an electrophysiologic study. For each VT, rapid ventricular pacing was attempted from the apex of the right ventricle at a cycle length which was 20 ms shorter than that of VT and repeated after a decrement of the cycle length in steps of 10 ms until the VT was terminated or accelerated. All 16 VTs could be entrained by the rapid pacing, and 13 of the 16 VTs (81%) were terminated, whereas pacing-induced acceleration was observed in the other 3 VTs of the 3 patients. VT cycle length (VTCL), block cycle length (BCL) which was defined as the longest VT interrupting paced cycle length, %BCL/VTCL and entrainment zone which was defined as VTCL minus BCL, varied in each VT morphology of each patient. In two patients, antitachycardia pacing was effective in all VT morphologies and the maximum difference of the %BCL/VTCL among the pleomorphic VTs was less than 10%. Thus, antitachycardia pacing seemed to be beneficial for these patients. In the other 5 patients, a difference of more than 10% in %BCL/VTCL was observed among the pleomorphic VT morphologies and/or at least one VT morphology showed pacing-induced acceleration. Compared to the 13 terminated VTs, three accelerated VTs had a wide entrainment zone [160 +/- 44 vs 90 +/- 48 ms, p < 0.04] and small %BCL/VTCL [61 +/- 6 vs 77 +/- 11%,p<0.03]. In pleomorphic VTs associated with non-coronary artery diseases, responses to rapid pacing was not uniform; VT might be terminable or accelerated even in the same patient. We need to pay close attention when programming antitachycardia pacing in patients with pleomorphic VT.

Accelerated Idioventricular Rhythm↗

Clinical diagnosis of vertebrobasilar insufficiency: resident's case problem.

STUDY DESIGN: Resident's case problem. BACKGROUND: Vertigo and visual disturbances are common symptoms associated with vertebrobasilar insufficiency (VBI), but the physical examination procedures to verify the existence of VBI have not been validated in the literature. The objective of this resident's case problem is to demonstrate how a patient's complaint of vertigo and visual disturbances, combined with positive clinical examination findings, can be a potential medical screening tool for VBI. DIAGNOSIS: The patient in this report was initially referred to physical therapy for neck pain. However, the patient's chief concerns identified during the history were (1) vertigo, (2) visual disturbances, (3) headache, and (4) right shoulder region pain. Clinical VBI tests were performed, whereby the patient's vertigo and visual disturbances were reproduced with cervical spine extension. The patient was sent back to the referring physician to be evaluated for possible VBI. Diagnostic imaging tests were ordered. Carotid ultrasound revealed 80% to 90% stenosis in the proximal left internal carotid artery, and magnetic resonance angiography of the extracerebral vessels showed greater than 90% stenosis of the left internal carotid artery. DISCUSSION: VBI may be present in patients with subjective reports of vertigo and visual disturbances that are reproduced with VBI physical examination procedures.

Diagnosis, Differential↗

Study of the electric activity of the cirrhotic liver with identification of an electrohepatogram.

In a recent study we could characterize an electrohepatogram (EHG) for the normal liver which consisted of regular monophasic, positively deflected slow waves or pacesetter potentials (PPs). We proposed that the EHG might act as an investigative tool in the diagnosis of liver diseases. In this communication, we studied the electric activity of the liver in hepatic cirrhosis. 42 patients with liver cirrhosis (30 men, 12 women, mean age 41.2+/-14.3 years) and 20 healthy volunteers (14 men, 6 women, mean age 42.2+/-13.1), who acted as controls, were enrolled in the study. Three silver-silver chloride electrodes were applied, 3-4 cm apart, to the abdominal skin parallel to and 1.5-2 cm below the right costal margin. Two 20-minute recording sessions were performed for each subject. In contrast to the regular reproducible PPs recorded in the healthy volunteers, the PPs of the cirrhotic patients had irregular rhythm, frequency and amplitude with occasional silent (no PPs) areas. The registered waves were identical from the 3 electrodes in the same subject in the healthy controls, while differed from one electrode to the other in the cirrhotic patients. The "hepatoarrhythmic" pattern encountered in the cirrhotic liver was consistent and reproducible. An EHG could be identified for the cirrhotic liver. It exhibited a "hepatoarrhythmic pattern" due probably to loss of the lobular architecture of the liver and its replacement with regeneration nodules and fibrosis.

Adult↗

A computational model-based validation of Guyton's analysis of cardiac output and venous return curves.

Guyton developed a popular approach for understanding the factors responsible for cardiac output (CO) regulation in which 1) the heart-lung unit and systemic circulation are independently characterized via CO and venous return (VR) curves, and 2) average CO and right atrial pressure (RAP) of the intact circulation are predicted by graphically intersecting the curves. However, this approach is virtually impossible to verify experimentally. We theoretically evaluated the approach with respect to a nonlinear, computational model of the pulsatile heart and circulation. We developed two sets of open circulation models to generate CO and VR curves, differing by the manner in which average RAP was varied. One set applied constant RAPs, while the other set applied pulsatile RAPs. Accurate prediction of intact, average CO and RAP was achieved only by intersecting the CO and VR curves generated with pulsatile RAPs because of the pulsatility and nonlinearity (e.g., systemic venous collapse) of the intact model. The CO and VR curves generated with pulsatile RAPs were also practically independent. This theoretical study therefore supports the validity of Guyton's graphical analysis.

Atrial Function, Right↗