Prior information and oculomotor initiation: the effect of cues in gaps

Eye movements reflect not only an important output of various neural control systems, but also often reflect cognitive processing. For example, saccades are frequently used as a behavioural index of attentional processing. A second important eye movement type, smooth pursuit (SP), has received much less attention in this regard. These two types of eye movement were classically thought of as being separate, but recent results have suggested a closer linkage of their control mechanisms and perhaps their interactions with cognitive processes. Prior information, in the form of cues, alters saccade latency leading to characteristic cueing effects. When the period between the appearance of the cue and the appearance of the saccade target is sufficiently long, the latency of saccades to targets appearing at cued locations is increased. This "inhibition of return" is enhanced by a second type of stimulus manipulation, the early removal of the fixation target a few hundred milliseconds before the target appears (the gap paradigm). In the current experiments, the effect of cues, and interactions between cues and long gaps were investigated. In the main pursuit experiment, and in a separate saccade experiment, subjects were presented with interleaved runs of tasks with and without long gaps (gap duration = 1 s), and with and without cues. In tasks without cues, SP latency was reduced by long gaps (mean reduction 8 ms); unexpectedly, saccade latency for non-cue tasks was increased by long gaps (mean increase 41 ms). In a control experiment with only non-cue tasks, in which SP and saccade gap and non-gap tasks were run together, SP latency was again reduced in gap tasks, while saccade latency was increased, but by much less than in the first experiment. Analysis of individual subjects' data showed that while gaps increased saccade latency in two subjects who had participated in the main experiment (in which cues and gaps had been combined), in two naive subjects long gaps did not affect saccade latency. In the main pursuit experiment, cues had both spatially specific and non-spatially specific (warning) effects on pursuit latency. In non-gap conditions, latency was greater when contralateral cues were presented 250 ms prior to the appearance of the pursuit target, compared to ipsilateral cues, a pattern of effect consistent with inhibition of return. However, this was reversed when cues appeared during a gap--contralateral cues increased while ipsilateral cues decreased latency. For saccades, as expected, in both gap and non-gap conditions, cue effects were consistent with inhibition of return (latency was lower with contralateral cues), and the inhibition of return effect was larger in gap, compared to non-gap conditions. The results suggest that, in appropriate contexts (or as a result of appropriate training), there are distinct inhibitory mechanisms that operate on saccades but not pursuit. What appears to be an inhibition of return effect on pursuit latency when static cues are presented in pursuit tasks, may be better understood as the product of a modulation of mechanisms active in pursuit initiation, perhaps related to motion processing. In contrast to some recent evidence suggesting a close anatomical and functional linkage between pursuit and saccade initiation, the results are consistent with the involvement of a wider range of mechanisms, or a greater degree of flexibility, in programming the initiation of these two oculomotor behaviours.     

骨骼肌钠通道α1亚基基因R1129Q新突变导致正常钾和低钾性周期性瘫痪一家系

目的 报道1个骨骼肌钠通道α1亚基(SCN4A)基因新突变导致的正常钾和低钾性周期性瘫痪家系的临床和病理改变特点.方法 本家系为常染色体显性遗传,共有9例患者,男性4例,女性5例,发病年龄7～25岁.5例患者为正常钾性周期性瘫痪,其中4例伴随肌强直症状;3例患者为低钾性周期性瘫痪;1例发作时血钾浓度不详.对先证者进行左肱二头肌活体组织检查.先证者和7例家系患者、3名无症状家系成员以及50名健康人行SCN4A基因测序.结果 先证者的肌纤维出现轻度肥大和萎缩,伴随核内移和肌纤维内空泡,部分肌纤维内氧化酶分布异常.所有患者均存在SCN4A基因的R1129Q突变,3名无症状家系成员以及50名健康对照无此突变.结论 SCN4A基因R1129Q新突变在同一家系内可以导致低血钾性和正常血钾性周期性瘫痪共存.     

Gene expression in blood of subjects with Duchenne muscular dystrophy

The objective of this study was to examine RNA expression in blood of subjects with Duchenne muscular dystrophy (DMD). Whole blood was collected into PAX gene tubes and RNA was isolated for 3- to 20-year-old males with DMD (n = 34) and for age- and gender-matched normal healthy controls (n = 21). DMD was confirmed by genetic testing in all subjects. RNA expression was measured on Affymetrix whole-genome human U133 Plus 2.0 GeneChips. Using a Benjamini–Hochberg false discovery rate of 0.05 to correct for multiple comparisons, an unpaired t test for DMD versus controls yielded 10,763 regulated probes with no fold change cutoff, 1,467 probes with >|1.5|-fold change, 191 probes with >|2.0|-fold change, and 59 probes with a >|2.5|-fold change. These genes (probes) separated DMD from controls using cluster analyses. Almost all of the genes regulated in peripheral blood were different from the genes reported to be regulated in diseased muscle of subjects with DMD. It is proposed that the genes regulated in blood of subjects with Duchenne muscular dystrophy are indicative, at least in part, of the immune response to the diseased DMD muscle. The regulated genes might be used to monitor therapy or provide novel targets for immune-directed therapy for DMD. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Coordination of gaze and hand movements for tracking and tracing in 3D

In this study we have investigated movements in three-dimensional space. Since most studies have investigated planar movements (like ellipses, cloverleaf shapes and “figure eights”) we have compared two generalizations of the two-thirds power law to three dimensions. In particular we have tested whether the two-thirds power law could be best described by tangential velocity and curvature in a plane (compatible with the idea of planar segmentation) or whether tangential velocity and curvature should be calculated in three dimensions. We defined total curvature in three dimensions as the square root of the sum of curvature squared and torsion squared. The results demonstrate that most of the variance is explained by tangential velocity and total curvature. This indicates that all three orthogonal components of movements in 3D are equally important and that movements are truly 3D and do not reflect a concatenation of 2D planar movement segments.In addition, we have studied the coordination of eye and hand movements in 3D by measuring binocular eye movements while subjects move the finger along a curved path. The results show that the directional component and finger position almost superimpose when subjects track a target moving in 3D. However, the vergence component of gaze leads finger position by about 250 msec. For drawing (tracing) the path of a visible 3D shape, the directional component of gaze leads finger position by about 225 msec, and the vergence component leads finger position by about 400 msec. These results are compatible with the idea that gaze leads hand position during drawing movement to assist prediction and planning of hand position in 3D space.     

A soluble activin type IIB receptor improves function in a mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurologic disease characterized by progressive weakness that results in death within a few years of onset by respiratory failure. Myostatin is a member of the TGF-β superfamily that is predominantly expressed in muscle and acts as a negative regulator of muscle growth. Attenuating myostatin has previously been shown to produce increased muscle mass and strength in normal and disease animal models. In this study, a mouse model of ALS (SOD1^G93A transgenic mice) was treated with a soluble activin receptor, type IIB (ActRIIB.mFc) which is a putative endogenous signaling receptor for myostatin in addition to other ligands of the TGF-β superfamily. ActRIIB.mFc treatment produces a delay in the onset of weakness, an increase in body weight and grip strength, and an enlargement of muscle size whether initiated pre-symptomatically or after symptom onset. Treatment with ActRIIB.mFc did not increase survival or neuromuscular junction innervation in SOD1^G93A transgenic mice. Pharmacologic treatment with ActRIIB.mFc was superior in all measurements to genetic deletion of myostatin in SOD1^G93A transgenic mice. The improved function of SOD1^G93A transgenic mice following treatment with ActRIIB.mFc is encouraging for the development of TGF-β pathway inhibitors to increase muscle strength in patients with ALS.     

The effect of the whole extract of common ivy (Hedera helix) leaves and selected active substances on the motoric activity of rat isolated stomach strips

Ethnopharmacological relevance

The long tradition of using the dry extract of Hedera helix (common ivy) leaves in traditional and contemporary alternative medicine caused that many biological and pharmacological studies have been aimed at evaluating the effects of ivy. Some of the results suggest that Hedera helix extract possesses bronchodilatatory and antispasmodic activity. On the other hand, the symptoms of ivy intoxication in human and animals, as well as adverse-reactions observed during the therapy with ivy-based pharmaceuticals, indicate rather stimulant effect of the plant on smooth muscle. Thus, the aim of this study was to evaluate the effect of two main active substances extracted from the plant (α-hederin and hederacoside C) and the whole dry extract of Hedera helix on the gut motility.

Materials and methods

The experiments were carried out on isolated stomach corpus and fundus strips. The tissues were isolated from rats. The experiments were performed in isotonic conditions. The results are expressed as the percent of the reaction caused by a reference contractile substance, acetylcholine.

Results and conclusions

The obtained results revealed that α-hederin applied in the concentration ranged from 25 to 320 μM significantly changed the spontaneous motoric activity of rat stomach smooth muscle. The observed reaction had always the same character, a contraction, and its force was concentration dependent. The second tested saponin, hederacoside C, did not alter the motility of rat isolated stomach corpus and fundus strips when administered in the concentration up to 100 μM, however, if applied in the concentration of 350 μM it induced a remarkable concentration of smooth muscle. Eventually, the whole extract of Hedera helix in a dose containing 60 μM of hederacoside C produced a strong contraction which strength was comparable with the reaction generated by acetylcholine. According to the results, it is very likely that α-hederin, but not hederacoside C contributes to the contractile response of isolated stomach corpus and fundus strips to the application of Hedera helix leaves’ extract.     

Age and gender influence on maximal bite force and masticatory muscles thickness

The present study aimed investigate the age and gender influence on maximal molar bite force and at outlining the criteria for normal masticatory muscle development in a sample of 177 Brazilian Caucasian dentate individuals aged 7-80 years divided into five age groups: I (7-12 years), II (13-20 years), III (21-40 years), IV (41-60 years), and V (61-80 years). Except for Group V, which comprised nine women and eight men, all groups were equally divided in respect to gender (20 M/20 F). Bite force was recorded with a mouth-adapted 1000 N dynamometer and the highest out of three records was regarded as the maximal bite force. The data were submitted to multivariate statistical analysis (SPSS 17.0 p < 0.05). Effects of group and gender were found, but no interactions between them. The ANOVA showed significant differences between groups bilaterally. Bonferroni's test showed that group I had significantly lower bite force means at both sides as compared to all groups, except group V. No differences were found between the left and right sides. In all the groups, gender was found to be a significant factor associated with maximal bite force. A global comparison including all the subjects and measures showed that the means of men were approximately 30% higher than those of women. Within-group comparisons yielded similar results in all groups. Muscle thickness was measured with a SonoSite Titan ultrasound tool using a high-resolution real-time 56 mm/10 MHz linear-array transducer. Three ultrasound images were obtained from the bilateral masseter and temporal muscles at rest and at maximal voluntary contraction. The means of the three measures in each clinical condition were analyzed with multivariate statistical analysis (SPSS 17.0 p < 0.05). A gradual increase in thickness of the masseter and temporal muscles was found both at rest and maximal voluntary contraction for groups I to IV, whereas a decrease in muscle thickness was observed in group V. Multivariate analysis showed that in both conditions there was an effect of group and gender. The study of the development of the stomatognathic system in relation to age and gender can provide useful data for the identification of normal and impaired functioning patterns. The results of this study indicate that age and gender are associated with structural and functional alterations in the muscles of the stomatognathic system.     

Thromboxane A2 receptor and MaxiK-channel intimate interaction supports channel trans-inhibition independent of G-protein activation

Large conductance voltage- and calcium-activated potassium channels (MaxiK, BK_Ca) are well known for sustaining cerebral and coronary arterial tone and for their linkage to vasodilator β-adrenergic receptors. However, how MaxiK channels are linked to counterbalancing vasoconstrictor receptors is unknown. Here, we show that vasopressive thromboxane A2 receptors (TP) can intimately couple with and inhibit MaxiK channels. Activation of the receptor with its agonist trans-inhibits MaxiK independently of G-protein activation. This unconventional mechanism is supported by independent lines of evidence: (i) inhibition of MaxiK current by thromboxane A2 mimetic, U46619, occurs even when G-protein activity is suppressed; (ii) MaxiK and TP physically associate and display a high degree of proximity; and (iii) Förster resonance energy transfer occurs between fluorescently labeled MaxiK and TP, supporting a direct interaction. The molecular mechanism of MaxiK–TP intimate interaction involves the receptor''s first intracellular loop and C terminus, and it entails the voltage-sensing conduction cassette of MaxiK channel. Further, physiological evidence of MaxiK–TP physical interaction is given in human coronaries and rat aorta, and by confirming TP role (with antagonist SQ29,548) in the U46619-induced MaxiK inhibition in human coronaries. We propose that vasoconstrictor TP receptor and MaxiK-channel direct interaction facilitates G-protein–independent TP to MaxiK trans-inhibition, which would promote vasoconstriction.     

Effect of botulinum toxin injection in the rectus femoris on stiff-knee gait in people with stroke: a prospective observational study

Stoquart GG, Detrembleur C, Palumbo S, Deltombe T, Lejeune TM. Effect of botulinum toxin injection in the rectus femoris on stiff-knee gait in people with stroke: a prospective observational study.

Objective

To study the effect of botulinum toxin type A (BTX-A) injection in the rectus femoris on the decreased knee flexion during the swing phase of gait (stiff-knee gait) in people with stroke.

Design

Intervention study (before-after trial) with an observational design.

Setting

Outpatient rehabilitation clinic and gait laboratory.

Participants

Nineteen chronic hemiparetic adults presenting with stiff-knee gait.

Intervention

Injection of 200U of BTX-A (Botox) into the rectus femoris.

Main Outcome Measures

Before and 2 months after BTX-A rectus femoris injection: Stroke Impairment Assessment Set (SIAS), Duncan-Ely test, and an instrumented gait analysis.

Results

Median SIAS score improved from 53 (range, 36−65) to 57 (range, 42−70) (signed-rank test, P=.005) and the Duncan-Ely score from 3 (range, 1−3) to 1 (range, 0−3) (P<.001). In gait analysis, mean (± standard deviation) maximum knee flexion improved from 26°±13° to 31°±14° during the swing phase (paired t test, P<.001), knee flexion speed at toe-off improved from 82°±63° to 112°±75°/s (P=.009), and knee negative joint power (eccentric muscular contraction) improved from −.27±.23 to −.37±.26W/kg (P<.001). The 4 patients who almost did not flex the knee (<10°) before the BTX-A rectus femoris injection did not improve after the injection. The other 14 patients who flexed the knee more than 10° before the BTX-A rectus femoris injection decreased the walking energy cost from 5.4±1.6 to 4.6±1.3J·kg⁻¹·m⁻¹ (P=.006).

Conclusions

BTX-A rectus femoris injection may be beneficial in patients with a stiff-knee gait after stroke, particularly in patients with some knee flexion (>10°).