bluuebunny/crossref_metadata_2025 huggingface dataset:
Model for Intersegmental Coordination of Leech Swimming: Central and Sensory Mechanisms
Authors: Cang Jianhua , Friesen W. Otto
Published: December 2017

Sensory feedback as well as the coupling signals within the CNS are essential for leeches to produce intersegmental phase relationships in body movements appropriate for swimming behavior. To study the interactions between the central pattern generator (CPG) and peripheral feedback in controlling intersegmental coordination, we have constructed a computational model for the leech swimming system with physiologically realistic parameters. First, the leech swimming CPG is simulated by a chain of phase oscillators coupled by three channels of coordinating signals. The activity phase, the projection direction, and the phase response curve (PRC) of each channel are based on the identified intersegmental interneuron network. Output of this largely constrained model produces stable coordination in the simulated CPG with average phase lags of 8–10°/segment in the period range from 0.5 to 1.5 s, similar to those observed in isolated nerve cords. The model also replicates the experimental finding that shorter chains of leech nerve cords have larger phase lags per segment. Sensory inputs, represented by stretch receptors, were subsequently incorporated into the CPG model. Each stretch receptor with its associated PRC, which was defined to mimic the experimental results of phase-dependent phase shifts of the central oscillator by the ventral stretch receptor, can alter the phase of the local central oscillator. Finally, mechanical interactions between the muscles from neighboring segments were simulated by PRCs linking adjacent stretch receptors. This model shows that interactions between neighboring muscles could globally increase the phase lags to the larger value required for the one-wavelength body form observed in freely swimming leeches. The full model also replicates the experimental observation that leeches with severed nerve cords have larger intersegmental phase lags than intact animals. The similarities between physiological and simulation results demonstrate that we have established a realistic model for the central and peripheral control of intersegmental coordination of leech swimming.
Motor-Unit Synchronization Alters Spike-Triggered Average Force in Simulated Contractions
Authors: Taylor Anna M. , Steege Julie W. , Enoka Roger M.
Published: December 2017

The purpose of the study was to quantify the effect of motor-unit synchronization on the spike-triggered average forces of a population of motor units. Muscle force was simulated by defining mechanical and activation characteristics of the motor units, specifying motor neuron discharge times, and imposing various levels of motor-unit synchronization. The model comprised 120 motor units. Simulations were performed for motor units 5–120 to compare the spike-triggered average responses in the presence and absence of motor-unit synchronization with the motor-unit twitch characteristics defined in the model. To synchronize motor-unit activity, selected motor-unit discharge times were adjusted; this kept the number of action potentials constant across the three levels of synchrony for each motor unit. Because there was some overlap of motor-unit twitches even at minimal discharge rates, the simulations indicated that spike-triggered averaging underestimates the twitch force of all motor units and the contraction time of motor units with contraction times longer than 49 ms. Although motor-unit synchronization increased the estimated twitch force and decreased the estimated contraction time of all motor units, spike-triggered average force changed systematically with the level of synchrony in motor units 59–120 (upper 90% of the range of twitch forces). However, the reduction in contraction time was similar for moderate and high synchrony. In conclusion, spike-triggered averaging appears to provide a biased estimate of the distribution of twitch properties for a population of motor units because twitch fusion causes an underestimation of twitch force for slow units and motor-unit synchronization causes an overestimation of force for fast motor units.
Effects of Bicuculline Methiodide on Fast (>200 Hz) Electrical Oscillations in Rat Somatosensory Cortex
Authors: Jones Michael S. , Barth Daniel S.
Published: December 2017

Fast oscillatory activity (more than ∼200 Hz) has been attracting increasing attention regarding its possible role in both normal brain function and epileptogenesis. Yet, its underlying cellular mechanism remains poorly understood. Our prior investigation of the phenomenon in rat somatosensory cortex indicated that fast oscillations result from repetitive synaptic activation of cortical pyramidal cells originating from GABAergic interneurons ( Jones et al. 2000 ). To test this hypothesis, the effects of topical application of the γ-aminobutyric acid-A (GABAA) antagonist bicuculline methiodide (BMI) on fast oscillations were examined. At subconvulsive concentrations (∼10 μM), BMI application resulted in a pronounced enhancement of fast activity, in some trials doubling the number of oscillatory cycles evoked by whisker stimulation. The amplitude and frequency of fast activity were not affected by BMI in a statistically significant fashion. At higher concentrations, BMI application resulted in the emergence of recurring spontaneous slow-wave discharges resembling interictal spikes (IIS) and the eventual onset of seizure. High-pass filtering of the IIS revealed that a burst of fast oscillations accompanied the spontaneous discharge. This activity was present in both the pre- and the postictal regimes, in which its morphology and spatial distribution were largely indistinguishable. These data indicate that fast cortical oscillations do not reflect GABAergic postsynaptic currents. An alternate account consistent with results observed to date is that this activity may instead arise from population spiking in pyramidal cells, possibly mediated by electrotonic coupling in a manner analogous to that underlying 200-Hz ripple in the hippocampus. Additionally, fast oscillations occur within spontaneous epileptiform discharges. However, at least under the present experimental conditions, they do not appear to be a reliable predictor of seizure onset nor an indicator of the seizure focus.
Sense of Taste in a New World Monkey, the Common Marmoset: Recordings From the Chorda Tympani and Glossopharyngeal Nerves
Authors: Danilova Vicktoria , Danilov Yuri , Roberts Thomas , Tinti Jean-Marie , Nofre Claude , Hellekant Göran
Published: December 2017

Whole nerve, as well as single fiber, responses in the chorda tympani proper (CT) and glossopharyngeal (NG) nerves of common marmosets were recorded during taste stimulation with three salts, four acids, six bitter compounds and more than 30 sweeteners. We recorded responses of 49 CT and 41 NG taste fibers. The hierarchical cluster analysis distinguished three major clusters in both CT and NG: S, Q, and H. The SCT fibers, 38% of all CT fibers, responded only to sweeteners. The SCT fibers did not respond during stimulation with salts, acids, and bitter compounds but exhibited off responses after citric and ascorbic acids, quinine hydrochloride (QHCl), and salts (in 80% of SCT fibers). SNG fibers, 50% of all NG fibers, also responded to sweeteners but not to stimuli of other taste qualities (except for citric acid, which stimulated 70% of the SNG fibers). Some sweeteners, including natural (the sweet proteins brazzein, monellin) and artificial [cyclamate, neohesperidin dihydrochalcone (NHDHC), N-3,5-dichlorophenyl- N′-(S)-α-methylbenzylguanidineacetate (DMGA), N-4-cyanophenylcarbamoyl-(R,S)-3-amino-3-(3,4-methylenedioxyphenyl) propionic acid (CAMPA)] did not elicit responses in the S fibers. In general, the response profiles of the SCT and SNG clusters were very similar, the correlation coefficient between the responses to sweeteners in these clusters was 0.94. Both the QCT and the QNG fibers (40 and 46% of all fibers) were predominantly responsive to bitter compounds, although their responses to the same set of bitter compounds were quite different. Sweeteners with sweet/bitter taste for humans also stimulated the Q clusters. The H clusters (22 and 3% of all fibers) were predominantly responsive to acids and did not respond to stimuli of other taste qualities. However, bitter stimuli, mainly QHCl, inhibited activity in 70% of HCT fibers. Among a total of 90 fibers from both nerves there was only 1 NaCl-best fiber in CT. We found, however, that 35% of the CT fibers reacted to salts with inhibition of activity during stimulation, followed by anoff response. This off response was diminished or eliminated by amiloride. These characteristics indicate that amiloride-sensitive sodium channels are involved in salt transduction in marmosets. In the two NG fibers responding to NaCl, we recorded neither suppression by amiloride nor off responses. Comparison of marmoset data with those of other nonhuman primates studied, rhesus and chimpanzee, demonstrates phylogenetic trends in the organization of taste system. This can help to uncover pathways of primate evolution.
Coupling of Calcium Homeostasis to Axonal Sodium in Axons of Mouse Optic Nerve
Authors: Verbny Yakov , Zhang Chuan-Li , Chiu Shing Yan
Published: December 2017

Axonal populations in neonatal and mature optic nerves were selectively stained with calcium dyes for analysis of calcium homeostasis and its possible coupling to axonal Na. Repetitive nerve stimulation causes a rise in axonal [Ca2+]i the posttetanus recovery of which is impeded by increasing the number of action potentials in the tetanus. This effect is augmented in 4-aminopyridine (4-AP; 1 mM), which dramatically increases the calcium and presumably sodium load during the tetanus. Increasing axonal [Na]i with the Na-ionophore monensin (4–50 μM) and ouabain (30 μM) retards posttetanus calcium decline, suggesting that efficient calcium clearance depends on a low level of axonal [Na]i. Posttetanus calcium clearance is not affected by K-mediated depolarization. To further examine coupling between axonal [Na]i and [Ca2+]i, the resting axonal [Ca2+]i was monitored as axonal [Na+]i was elevated with ouabain, veratridine, and monensin. In all cases, elevation of axonal [Na+]i evokes a calcium influx into axons. This influx is unrelated to activation of calcium channels but is consistent with calcium influx via reversal of the Na/Ca exchanger expected as a consequence of axonal [Na+]i elevation. In conclusion, this study demonstrates that calcium homeostasis in the axons of the optic nerve is strongly coupled to axonal [Na+]i in a manner consistent with the Na/Ca exchanger playing a major role in extruding calcium following nerve activity.
Tumor Necrosis Factor (TNF) Ligand and TNF Receptor Deficiency Affects Sleep and the Sleep EEG
Authors: Deboer Tom , Fontana Adriano , Tobler Irene
Published: December 2017

Tumor necrosis factor (TNF) and lymphotoxin-α (LT-α) are proinflammatory cytokines involved in host defense and pathogenesis of various diseases. In addition, there is evidence that TNF is involved in sleep. TNF and LT-α both bind to the tumor necrosis factor receptors (TNFR). Recently, it was shown that TNF receptor 1 (TNFR1) knockout mice (R1KO) sleep less during the light period than controls. We investigated the effect of a TNF and LT-α double deficiency on sleep in mice (Ligand KO) and compared their sleep with that of R1KO, TNFR2 knockout (R2KO) mice, and wild-type (WT) controls. All mice were adapted to a 12:12 h light:dark cycle and their electroencephalographs (EEG) and electromyographs (EMG) were continuously recorded during a baseline day, 6-h sleep deprivation (SD), and 18-h recovery. Ligand KO and R2KO had 15% less rapid eye movement (REM) sleep during the baseline light period due to a reduction in REM sleep episode frequency. After SD, all genotypes showed an initial increase in slow-wave activity (SWA) (EEG power density between 0.75 and 4.0 Hz) in non-REM sleep, which gradually declined in the following hours. In Ligand KO the increase was mainly caused by an increase in fast SWA (2.75–4.0 Hz), which was also increased in R2KO. In contrast, in R1KO mice the increase was limited to the slow portion of SWA (0.75–2.5 Hz). R2KO and WT mice showed increases in both frequency ranges. The sub-division into fast and slow SWA frequencies corresponds to previous electrophysiological data where the two types of slow-waves were induced by either excitatory or inhibitory stimuli. Our data suggest that in Ligand KO the SWA increase is caused by an increase in excitatory input to the cortex, whereas in R1KO this input seems to be almost absent.
Functional Properties of Ryanodine Receptors in Hippocampal Neurons Change During Early Differentiation in Culture
Authors: Sukhareva Manana , Smith Susan V. , Maric Dragan , Barker Jeffery L.
Published: December 2017

6-((4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza- s-indacene-3-propionyl)amino)hexanoic acid ryanodine (BODIPY-ryanodine) binding and Ca2+imaging were used to study the properties of ryanodine receptors (RyRs) and cytoplasmic Ca2+(Ca[Formula: see text]) changes in neurons cultured from the embryonic rat hippocampus during the earliest stages of differentiation. Baseline Ca[Formula: see text]levels declined from 164 ± 5 (SD) nM at early stages to 70 ± 4 nM in differentiated neurons. Fluorescent BODIPY-ryanodine binding signals identified activated RyRs in somata, which were eliminated by removal of external Ca2+ or by blockage of Ca2+ entry through L-type but not N-type Ca2+ channels. The GABA synthesis inhibitor 3-mercaptopropionic acid completely abolished ryanodine binding. Caffeine or K+-depolarization inhibited the activity of RyRs at very early stages of differentiation but had stimulatory effects at later stages after a network of processes had formed. BayK-8644 stimulated RyRs throughout all regions of all differentiating cells. The results suggest that in differentiating embryonic hippocampal neurons the activity of RyRs is maintained via Ca2+ entering through L-type Ca2+ channels. The mode of activation of L-type voltage-gated Ca2+ channels with either membrane depolarization or specific pharmacological agents affects the coupled activity of RyRs differently as neurons differentiate processes and networks.
Responses of Primate Visual Cortical V4 Neurons to Simultaneously Presented Stimuli
Authors: Gawne Timothy J. , Martin Julie M.
Published: December 2017

We report here results from 45 primate V4 visual cortical neurons to the preattentive presentations of seven different patterns located in two separate areas of the same receptive field and to combinations of the patterns in the two locations. For many neurons, we could not determine any clear relationship for the responses to two simultaneous stimuli. However, for a substantial fraction of the neurons we found that the firing rate was well modeled as the maximum firing rate of each stimulus presented separately. It has previously been proposed that taking the maximum of the inputs (“MAX” operator) could be a useful operation for neurons in visual cortex, although there has until now been little direct physiological evidence for this hypothesis. Our results here provide direct support for the hypothesis that the MAX operator plays a significant (although certainly not exclusive) role in generating the receptive field properties of visual cortical neurons.
Low-Frequency Oscillations (<0.3 Hz) in the Electromyographic (EMG) Activity of the Human Trapezius Muscle During Sleep
Authors: Westgaard R. H. , Bonato P. , Holte K. A.
Published: December 2017

The surface electromyographic (EMG) signal from right and left trapezius muscles and the heart rate were recorded over 24 h in 27 healthy female subjects. The root-mean-square (RMS) value of the surface EMG signals and the heartbeat interval time series were calculated with a time resolution of 0.2 s. The EMG activity during sleep showed long periods with stable mean amplitude, modulated by rhythmic components in the frequency range 0.05–0.2 Hz. The ratio between the amplitude of the oscillatory components and the mean amplitude of the EMG signal was approximately constant over the range within which the phenomenon was observed, corresponding to a peak-to-peak oscillatory amplitude of ∼10% of the mean amplitude. The duration of the periods with stable mean amplitude ranged from a few minutes to ∼1 h, usually interrupted by a sudden change in the activity level or by cessation of the muscle activity. Right and left trapezius muscles presented the same pattern of FM. In supplementary experiments, rhythmic muscle activity pattern was also demonstrated in the upper extremity muscles of deltoid, biceps, and forearm flexor muscles. There was no apparent association between the rhythmic components in the muscle activity pattern and the heart rate variability. To our knowledge, this is the first time that the above-described pattern of EMG activity during sleep is documented. On reanalysis of earlier recorded trapezius motor unit firing pattern in experiments on awake subjects in a situation with mental stress, low-FM of firing with similar frequency content was detected. Possible sources of rhythmic excitation of trapezius motoneurons include slow-wave cortical oscillations represented in descending cortico-spinal pathways, and/or activation by monoaminergic pathways originating in the brain stem reticular formation. The analysis of muscle activity patterns may provide an important new tool to study neural mechanisms in human sleep.
Differential Processing Patterns of Motor Information Via Striatopallidal and Striatonigral Projections
Authors: Kaneda Katsuyuki , Nambu Atsushi , Tokuno Hironobu , Takada Masahiko
Published: December 2017

The functional loop linking the frontal lobe and the basal ganglia plays an important role in the control of motor behaviors. To delineate the principal features of motor information processing in the cortico-basal ganglia loop, the present study aimed at investigating how corticostriatal inputs from the primary motor cortex (MI) and the supplementary motor area (SMA) are transposed onto the pallidal complex and the substantia nigra. In macaque monkeys, stimulating electrodes were chronically implanted into identified forelimb representations of the MI and SMA. Subsequently, the distribution of neurons exhibiting orthodromic responses was examined in the caudal putamen to demarcate striatal zones receiving inputs separately or confluently from the MI and SMA. Finally, anterograde double labeling was performed by paired injections of tracers into two of three identified zones: the MI-recipient zone, SMA-recipient zone, and the convergent zone. Data have revealed that inputs from the MI-recipient and SMA-recipient striatal zones were substantially segregated in the pallidal complex and that those from the convergent zone were distributed to fill in blanks made by terminal bands derived from the MI and SMA. On the other hand, striatonigral inputs from the SMA-recipient and convergent zones of the putamen largely overlapped, while the input from the MI-recipient zone was minimal. The present results clearly indicate that the mode to process corticostriatal motor information through the striatopallidal and striatonigral projections is target-dependent, such that the parallel versus convergent rules govern the arrangement of striatopallidal or striatonigral inputs, respectively.
Involvement of Calcium in Rhythmic Activity Induced by Disinhibition in Cultured Spinal Cord Networks
Authors: Darbon Pascal , Pignier Christophe , Niggli Ernst , Streit Jürg
Published: December 2017

Disinhibition of rat spinal networks induces a spontaneous rhythmic bursting activity. The major mechanisms involved in the generation of such a bursting are intrinsic neuronal firing of a subpopulation of interneurons, recruitment of the network by recurrent excitation, and autoregulation of neuronal excitability. We have combined whole cell recording with calcium imaging and flash photolysis of caged-calcium to investigate the contribution of [Ca2+]i to rhythmogenesis. We found that calcium mainly enters the neurons through voltage-activated calcium channels and N-methyl-d-aspartate (NMDA) channels as a consequence of the depolarization during the bursts. However, [Ca2+]i could neither predict the start nor the termination of bursts and is therefore not critically involved in rhythmogenesis. Also calcium-induced calcium release is not involved as a primary mechanism in bursting activity. From these findings, we conclude that in the rhythmic activity induced by disinhibition of spinal cord networks, the loading of the cells with calcium is a consequence of bursting and does not functionally contribute to rhythm generation.
Role of Synaptic Metabotropic Glutamate Receptors in Epileptiform Discharges in Hippocampal Slices
Authors: Lee Angela C. , Wong Robert K. S. , Chuang Shih-Chieh , Shin Hee-Sup , Bianchi Riccardo
Published: December 2017

Application of group I metabotropic glutamate receptor (mGluR) agonists elicits seizure discharges in vivo and prolonged ictal-like activity in in vitro brain slices. In this study we examined 1) if group I mGluRs are activated by synaptically released glutamate during epileptiform discharges induced by convulsants in hippocampal slices and, if so, 2) whether the synaptically activated mGluRs contribute to the pattern of the epileptiform discharges. The GABAAreceptor antagonist bicuculline (50 μM) was applied to induce short synchronized bursts of ∼250 ms in mouse hippocampal slices. Addition of 4-aminopyridine (4-AP; 100 μM) prolonged these bursts to 0.7–2 s. The mGluR1 antagonist ( S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acid (LY 367385; 25–100 μM) and the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP; 10–50 μM), applied separately, significantly reduced the duration of the synchronized discharges. The effects of these antagonists were additive when applied together, suggesting that mGluR1 and mGluR5 exert independent actions on the epileptiform bursts. In phospholipase C β1 (PLCβ1) knockout mice, bicuculline and 4-AP elicited prolonged synchronized discharges of comparable duration as those observed in slices from wild-type littermates. Furthermore, mGluR1 and mGluR5 antagonists reduced the duration of the epileptiform discharges to the same extent as they did in the wild-type preparations. The results suggest that mGluR1 and mGluR5 are activated synaptically during prolonged epileptiform discharges induced by bicuculline and 4-AP. Synaptic activation of these receptors extended the duration of synchronized discharges. In addition, the data indicate that the synaptic effects of the group I mGluRs on the duration of epileptiform discharges were mediated by a PLCβ1-independent mechanism.
Activation of mGluR5 Modulates GABAAReceptor Function in Retinal Amacrine Cells
Authors: Hoffpauir Brian K. , Gleason Evanna L.
Published: December 2017

Amacrine cells in the vertebrate retina receive glutamatergic input from bipolar cells and make synapses onto bipolar cells, ganglion cells, and other amacrine cells. Recent studies indicate that amacrine cells express metabotropic glutamate receptors (mGluRs) and that signaling within the inner plexiform layer (IPL) of the retina might be modulated by mGluR activity. This study tests the hypothesis that activation of mGluR5 modulates GABAAreceptor function in retinal amacrine cells. Whole cell voltage-clamp recordings were combined with pharmacology to establish the identity of the ionotropic GABA receptors expressed in primary cultures of chick amacrine cells and to determine how mGluR5 activity affected the behavior of those receptors. Application of GABA (20 μM) produced currents that reversed at −58.2 ± 0.9 mV, near the predicted Cl−reversal potential of −59 mV. The GABAAreceptor antagonist, bicuculline (50 μM), completely blocked the GABA-gated currents. cis-4-Aminocrotonic acid (CACA; 100 μM), a GABACreceptor agonist, produced small currents that were not blocked by the GABACantagonist, (1,2,5,6-tetrahydropyridine-4-yl) methylphosphinic acid (TPMPA; 20 μM), but were completely blocked by bicuculline. These results indicate that cultured amacrine cells express GABAAreceptors exclusively. Activating mGluR5 with ( RS)-2-chloro-5-hydroxyphenylglycine (CHPG; 300 μM) enhanced GABA-gated currents by 10.0 ± 1.5%. Buffering internal Ca2+with BAPTA (10 mM) blocked the CHPG-dependent enhancement. Activation of PKC with the cell-permeable PKC activators (−)-7-octylindolactam V, phorbol 12-myristate 13 acetate (PMA), or 1-oleoyl-2-acetyl-sn-glycerol (OAG) also enhanced GABA-gated currents in a dose-dependent manner. Preactivation of PKC occluded the mGluR5-dependent enhancement, and inhibition of Ca-dependent PKC isotypes with Gö6976 (35 nM) suppressed the effects of mGluR5 activation, suggesting that mGluR5 and PKC are part of the same pathway. To determine if mGluR5-dependent enhancement occurred at synaptic GABAAreceptors, postsynaptic currents were recorded in the presence of CHPG. On average, the mean amplitudes of the quantal events were increased by about 18% when mGluR5 was activated. These results indicate that activation of mGluR5 enhances GABA-gated current in cultured amacrine cells in a manner that is both Ca2+- and PKC-dependent. These results support the possibility that glutamate released from bipolar cells can modulate the function of GABAergic amacrine cells and alter signaling in the inner plexiform layer.
Distinct Nature of Directional Signals Among Parietal Cortical Areas During Visual Guidance
Authors: Eskandar Emad N. , Assad John A.
Published: December 2017

We examined neuronal signals in the monkey medial superior temporal area (MST), the medial intraparietal area (MIP), and the lateral intraparietal area (LIP) during visually guided hand movements. Two animals were trained to use a joystick to guide a spot to a target. Many neurons responded in a direction-selective manner in this guidance task. We tested whether the direction selectivity depended on the direction of the stimulus spot or the direction of the hand movement. First, in some trials, the moving spot disappeared transiently. Second, the mapping between the hand direction and the spot direction was reversed on alternate blocks of trials. Third, we recorded the spot's movement while the animals moved the joystick and then played back that movement while the animals fixated without moving the joystick. Neurons in the three parietal areas conveyed distinct directional information. MST neurons were active and directional only on visible trials in both joystick-movement mode and playback mode and were not affected by the direction of hand movement. MIP neurons were mainly directional with respect to the hand movement, although some MIP neurons were also selective for stimulus direction. MIP neurons were much less active in playback mode. LIP neurons were active and directional in both joystick-movement mode and playback mode. Directional signals in LIP were unrelated to planning saccades. The selectivity of LIP neurons also became evident hundreds of milliseconds before the start of movement. Since the direction of movement was consistent throughout a block of trials, these signals could provide a prediction of the upcoming direction of motion. We tested this by alternating blocks of trials in which the direction was consistent or randomized. The direction selectivity developed earlier on trials in which the upcoming direction could be predicted. These results suggest that LIP neurons combine “bottom-up” visual motion signals with extraretinal, predictive signals about stimulus motion.
Learning of Sequences of Finger Movements and Timing: Frontal Lobe and Action-Oriented Representation
Authors: Sakai Katsuyuki , Ramnani Narender , Passingham Richard E.
Published: December 2017

Motor sequence learning involves learning of a sequence of effectors with which to execute a series of movements and learning of a sequence of timings at which to execute the movements. In this study, we have segregated the neural correlates of the two learning mechanisms. Moreover, we have found an interaction between the two learning mechanisms in the frontal areas, which we claim as suggesting action-oriented coding in the frontal lobe. We used positron emission tomography and compared three learning conditions with a visuo-motor control condition. In two learning conditions, the subjects learned either a sequence of finger movements with random timing or a sequence of timing with random use of fingers. In the third condition the subjects learned to execute a sequence of specific finger movements at specific timing; we argue that it was only in this condition that the motor sequence was coded as an action-oriented representation. By looking for condition by session interactions (learning vs. control conditions over sessions), we have removed nonspecific time effects and identified areas that showed a learning-related increment of activation during learning. Learning of a finger sequence was associated with an increment of activation in the right intraparietal sulcus region and medial parietal cortex, whereas learning of a timing sequence was associated with an increment of activation in the lateral cerebellum, suggesting separate mechanisms for learning effector and temporal sequences. The left intraparietal sulcus region showed an increment of activation in learning of both finger and timing sequences, suggesting an overlap between the two learning mechanisms. We also found that the mid-dorsolateral prefrontal cortex, together with the medial and lateral premotor areas, became increasingly active when subjects learned a sequence that specified both fingers and timing, that is, when subjects were able to prepare specific motor action. These areas were not active when subjects learned a sequence that specified fingers or timing alone, that is, when subjects were still dependent on external stimuli as to the timing or fingers with which to execute the movements. Frontal areas may integrate the effector and temporal information of a motor sequence and implement an action-oriented representation so as to perform a motor sequence accurately and quickly. We also found that the mid-dorsolateral prefrontal cortex was distinguished from the ventrolateral prefrontal cortex and anterior fronto-polar cortex, which showed sustained activity throughout learning sessions and did not show either an increment or decrement of activation.
Ankle Muscle Stiffness Alone Cannot Stabilize Balance During Quiet Standing
Authors: Morasso Pietro G. , Sanguineti Vittorio
Published: December 2017

This communication addresses again the hypothesis that the stabilization of balance during quiet standing is achieved by the stiffness of ankle muscles without anticipatory active control. It is shown that a recently proposed method of estimating ankle stiffness directly from the analysis of the posturographic data is incorrect because it ignores the modulation of motoneuronal activity and grossly overestimates the real range of values in relation with the critical value of stiffness. Moreover, a new simulation study with a realistic model of ankle muscles demonstrates the mechanical instability of the system when there is no anticipatory control input. However, the simulations also suggest that in normal subjects the active stiffness mechanisms of stabilization have similar weights in determining the restoring forces that are necessary for preventing the body from falling.
Effects of Image Motion in the Dorsal Premotor Cortex During Planning of an Arm Movement
Authors: Ochiai Tetsuji , Mushiake Hajime , Tanji Jun
Published: December 2017

This study examined whether neuronal activity in the dorsal premotor cortex (PMd) covaries with image motion or actual movement of the arm while planning a target-capturing task when the motor task is guided by an image of the moving arm. For this purpose, we trained a monkey to capture a target on a video screen with the part of the arm displayed on the screen. The target-capturing body part was either the right or left side of the hand image. Because the actual arm movement was invisible, the motor task was guided by the arm image, which was at times right-left inverted on the screen. We found that neuronal activity in the PMd predominantly reflected arm-image movement rather than the actual arm movement, and for half of PMd neurons, the activity differed depending on the target-capturing body-part defined in the right or left side of the arm image.
Oral Yeast Colonization and Fungal Infections in Peritoneal Dialysis Patients: A Pilot Study
Authors: Simões-Silva Liliana , Silva Sara , Santos-Araujo Carla , Sousa Joana , Pestana Manuel , Araujo Ricardo , Soares-Silva Isabel , Sampaio-Maia Benedita
Published: December 2017

Peritonitis and exit-site infections are important complications in peritoneal dialysis (PD) patients that are occasionally caused by opportunistic fungi inhabiting distant body sites. In this study, the oral yeast colonization of PD patients and the antifungal susceptibility profile of the isolated yeasts were accessed and correlated with fungal infection episodes in the following 4 years. Saliva yeast colonization was accessed in 21 PD patients and 27 healthy controls by growth in CHROMagar-Candida® and 18S rRNA/ITS sequencing. PD patients presented a lower oral yeast prevalence when compared to controls, namely,Candida albicans. Other species were also isolated,Candida glabrataandCandida carpophila. The antifungal susceptibility profiles of these isolates revealed resistance to itraconazole, variable susceptibility to caspofungin, and higher MIC values of posaconazole compared to previous reports. The 4-year longitudinal evaluation of these patients revealedCandida parapsilosisandCandida zeylanoidesas PD-related exit-site infectious agents, but no correlation was found with oral yeast colonization. This pilot study suggests that oral yeast colonization may represent a limited risk for fungal infection development in PD patients. Oral yeast isolates presented a variable antifungal susceptibility profile, which may suggest resistance to some second-line drugs, highlighting the importance of antifungal susceptibility assessment in the clinical practice.
Iron and Cognitive Development: What Is the Evidence?
Authors: Larson Leila M. , Phiri Kamija S. , Pasricha Sant-Rayn
Published: December 2017

The theoretical irreversible damage that iron deficiency and iron deficiency anemia can exert on child development makes a compelling argument for action to alleviate the burden. However, a critical analysis of evidence from iron interventions in early life is necessary to determine whether and how iron interventions improve cognitive outcomes. Key iron interventions used in clinical and public health practice include oral iron supplementation and, in young children, iron-containing multiple micronutrient powders. This article examines the evidence to answer 4 main questions. (1) Does antenatal iron supplementation influence long-term child cognitive development? (2) Does oral iron supplementation in preschool children improve short-term cognitive development? (3) Does oral iron supplementation in older children improve cognitive development? And (4), can provision of iron harm cognitive development? Early trials indicated benefit from parenteral iron in young children regardless of anemia status. There also appears to be evidence for benefit using oral iron treatment on cognitive performance in anemic primary school children. However, antenatal and early childhood oral iron intervention studies show inconsistent effects on early and long-term childhood cognitive outcomes. These data suggest either that (a) effects from oral iron on cognitive development in young children are small or nonexistent or that (b) heterogeneity between trials and the low quality of many studies make assessment of effect difficult. Importantly, few large, placebo-controlled trials in under-2-year-old children in low-income settings assessing effects of iron interventions on cognition have been performed; high-quality, placebo-controlled, adequately powered trials of universal iron interventions on cognitive performance in young children are urgently needed to justify policies of universal iron intervention in this group.
Low- versus High-Dose and Early versus Late Parenteral Amino-Acid Administration in Very-Low-Birth-Weight Infants: A Systematic Review and Meta-Analysis
Authors: Leenders Erika K.S.M. , de Waard Marita , van Goudoever Johannes B.
Published: December 2017

Objectives: Providing parenteral amino acids to very-low-birth-weight infants during the first weeks of life is critical for adequate growth and neurodevelopment. However, there is no consensus about what dose is appropriate or when to initiate supplementation. As a result, daily practice varies among neonatal intensive care units. The objective of our study was to determine the effects of early parenteral amino-acid supplementation (within 24 h of birth) versus later initiation and high dose (>3.0 g/kg/day) versus a lower dose on growth and morbidities. Methods: A systematic review and meta-analysis of publications identified by searching PubMed, EMBASE, and Cochrane databases was conducted. Randomized controlled studies were eligible if information on growth was available. Results: The search identified 14 studies. No differences were observed in growth or morbidity after early or high-dose amino-acid supplementation, but for several outcomes, meta-analysis was not possible due to study heterogeneity. Initiation of amino acids within the first 24 h of life appeared to be safe and well tolerated, and leads more rapidly to a positive nitrogen balance. Conclusions: Administering a high dose (>3.0 g/kg/day) or an early dose (≤24 h) of parenteral amino acids is safe and well tolerated but does not offer significant benefits on growth. Further large-scale randomized controlled trials in preterm infants are needed to study the effects of early and high-dose amino acids on growth and morbidity more consistently and extensively.
Rapidly Progressive, Isolated Subretinal Leukemic Relapse: A Case Report
Authors: Gillette Thomas B. , Cabrera Michelle T. , Tarlock Katherine , Murphy Claire E. , Chisholm Karen M. , Stacey Andrew W.
Published: December 2017

Purpose: The aim of this paper is to describe a case of relapsed pediatric acute lymphoblastic leukemia (ALL) presenting as a rapidly progressive subretinal infiltrate, as diagnosed by ultrasound-guided fine needle aspiration (FNA). Methods: We conducted a clinical pathological retrospective chart review. Results: Eleven months after documented remission of T-cell ALL while on maintenance therapy, this 17-year-old patient presented with acute open angle glaucoma in the right eye. B-scan ultrasonography suggested total retinal detachment. Eight weeks later, based on routine cerebrospinal fluid analysis, the patient was diagnosed with central nervous system relapse of T-cell ALL. Repeat B-scan 1 week later showed a new hyperechoic subretinal mass. FNA of the mass confirmed leukemic infiltrate. The involved eye was enucleated, demonstrating leukemic cells throughout the subretinal space, choroid, and the optic nerve. Following hematopoietic stem cell transplant, the patient continues to maintain bone marrow remission 5 months after enucleation without involvement in the opposite eye. Conclusion: Retinal detachment in any patient with a history of leukemia should raise the possibility of relapse and may warrant aspiration/biopsy if other means of diagnosing relapse are inconclusive. Subretinal infiltrate may progress rapidly and prompt diagnosis is paramount to tailoring therapy and preserving vision.
Spontaneous Hepatitis B Seroclearance upon Development of Hepatocellular Carcinoma
Authors: Naimimohasses Sara , El Sherif Omar , Ashfaq Mohammad , Nolan Niamh , Iqbal Masood , McKiernan Susan , Norris Suzanne
Published: December 2017

The spontaneous seroclearance of hepatitis B upon development of a hepatocellular carcinoma (HCC) is extremely rare. To date, there has been one published case series reporting hepatitis B seroconversion following HCC resection. We describe two novel cases of spontaneous hepatitis B seroclearance following the development of HCC, prior to resection. Following resection, specimens were HBsAg- and HBcAg-negative in both tumor and peritumor tissues. Although the precise mechanism of this is poorly understood, nonuniform integration of hepatitis B virus DNA within the liver could lead to selective tumorigenesis of HBsAg-producing cells, explaining the observed clearance of serum HBsAg with the development of HCC.
Modified Colistin Regimen for Critically Ill Patients with Acute Renal Impairment and Continuous Renal Replacement Therapy
Authors: Menna Pierantonio , Salvatorelli Emanuela , Mattei Alessia , Cappiello Dario , Minotti Giorgio , Carassiti Massimiliano
Published: December 2017

Colistin is a last resort antibiotic to treat multidrug-resistant Gram-negative bacteria infections. Colistin is administered intravenously in the form of its inactive prodrug colistin methanesulfonate (CMS). For patients with acute kidney impairment and continuous renal replacement therapy high extracorporeal clearance may cause a substantial removal of active colistin from the bloodstream, eventually decreasing its antibacterial efficacy. Currently recommended doses of CMS may therefore be inadequate for these patients. We report on the potential value of a modified regimen that adopts a loading dose of CMS (bolus of 9 MU vs. conventional 3 MU every 8 h), followed by maintenance (3 MU every 8 h). Preliminary pharmacokinetic evidence for the feasibility and efficacy of this regimen is described for 2 patients.
Lateral Medullary Ischemic Infarct Caused by Posterior Inferior Cerebellar Artery Aneurysm
Authors: Malik Muhammad Taimur , Kenton III Edgar J. , Vanino Dana , Dalal Shamsher S. , Zand Ramin
Published: December 2017

Posterior inferior cerebellar artery (PICA) aneurysms are rare. The most common complication of intracranial aneurysms is rupture causing subarachnoid hemorrhage. Ischemic infarct, although more common in giant thrombosed aneurysms, is a very rare manifestation of small intracranial aneurysms. Here we describe a patient who presented with lateral medullary acute infarction associated with an ipsilateral, small (4 × 3.5 mm), unruptured and non-thrombosed PICA aneurysm.
Halo Sign and Eosinophilia: What Is Your Diagnosis?
Authors: Thevenet Florent , Beltramo Guillaume , Georges Marjolaine , Foignot Clément , Spanjaard Maximilien , Bonniaud Philippe
Published: December 2017

Blood eosinophilia associated with transient and migrating nodules with a halo sign on chest computed tomography scan should suggest larva migrans related to toxocariasis or ascaris suum.
Psychometric Properties of the MyotonPRO in Dementia Patients with Paratonia
Authors: Drenth Hans , Zuidema Sytse U. , Krijnen Wim P. , Bautmans Ivan , van der Schans Cees , Hobbelen Hans
Published: December 2017

Background: Paratonia is a distinctive form of hypertonia, causing loss of functional mobility in early stages of dementia to severe high muscle tone and pain in the late stages. For assessing and evaluating therapeutic interventions, objective instruments are required. Objective: Determine the psychometric properties of the MyotonPRO, a portable device that objectively measures muscle properties, in dementia patients with paratonia. Methods: Muscle properties were assessed with the MyotonPRO by 2 assessors within one session and repeated by the main researcher after 30 min and again after 6 months. Receiver operating characteristic curves were constructed for all MyotonPRO outcomes to discriminate between participants with (n = 70) and without paratonia (n = 82). In the participants with paratonia, correlation coefficients were established between the MyotonPRO outcomes and the Modified Ashworth Scale for paratonia (MAS-P) and muscle palpation. In participants with paratonia, reliability (intraclass correlation coefficient) and agreement values (standard error of measurement and minimal detectable change) were established. Longitudinal outcome from participants with paratonia throughout the study (n = 48) was used to establish the sensitivity for change (correlation coefficient) and responsiveness (minimal clinical important difference). Results: Included were 152 participants with dementia (mean [standard deviation] age of 83.5 [98.2]). The area under the curve ranged from 0.60 to 0.67 indicating the MyotonPRO is able to differentiate between participants with and without paratonia. The MyotonPRO explained 10-18% of the MAS-P score and 8-14% of the palpation score. Interclass correlation coefficients for interrater reliability ranged from 0.57 to 0.75 and from 0.54 to 0.71 for intrarater. The best agreement values were found for tone, elasticity, and stiffness. The change between baseline and 6 months in the MyotonPRO outcomes explained 8-13% of the change in the MAS-P scores. The minimal clinically important difference values were all smaller than the measurement error. Conclusion: The MyotonPRO is potentially applicable for cross-sectional studies between groups of paratonia patients and appears less suitable to measure intraindividual changes in paratonia. Because of the inherent variability in movement resistance in paratonia, the outcomes from the MyotonPRO should be interpreted with care; therefore, future research should focus on additional guidelines to increase the clinical interpretation and improving reproducibility.
Distribution, encounter rate and conservation status of Aquiloeurycea cafetalera (Caudata: Plethodontidae), a recently described Mexican salamander
Authors: Aguilar-López José Luis , Sandoval-Comte Adriana , Pineda Eduardo
Published: December 2017

The knowledge of the natural history of a species, its population traits and spatial distribution are essential to evaluate its risk of extinction and proposing strategies for its conservation. For poorly studied species inhabiting regions with a high degree of habitat conversion by anthropogenic activities, it is even more urgent to obtain this information. In this study, we carried out fieldwork and database analyses to obtain information on the ecology, natural history and spatial distribution of the plethodontid salamander Aquiloeurycea cafetalera, and we evaluated its conservation status according to the IUCN and the Mexican environmental agency (SEMARNAT). We found 109 individuals in 20 of the 43 localities visited (sampling effort = 1,174 person-hours). The salamander counts ranged from one to 21 individuals per locality and the average encounter rate was 21 salamanders per 100 person-hours of surveying, within a range from 2 to 117 salamanders. The current potential distribution calculated is about 2,000 km2 and fragmented, which means less than half of its original potential distribution. Our results suggest that it is necessary to include this species in biodiversity conservation programs because only a very small portion of its spatial distribution falls within natural protected areas.
A memória da infância e a formação da nação emergente em Luís Cardoso
Authors: Queiroga Mariene de Fátima Cordeiro , Paulino Vicente
Published: December 2017

Esse trabalho aborda a personagem da trilogia cardosiana, por hipótese, o próprio autor-narrador, como sujeito principal da sua obra e suas narrativas como a metáfora da formação do Estado nação Timor-Leste. O romancista é um sujeito que na expressão de Homi Bhabha:  aquele “que representa uma diferença ‘interior’, um sujeito que habita a borda de uma realidade ‘intervalar’. E a inscrição dessa existência fronteiriça consiste numa quietude do tempo e uma estranheza de enquadramento que ‘cria a imagem discursiva na encruzilhada entre história e literatura” (Bhabha, 1998:35).
Figurações da mulher no cinema de Lars von Trier
Authors: Rufinoni Simone Rossinetti
Published: December 2017

Partindo-se da recorrência de protagonistas mulheres na filmografia do diretor Lars von Trier, este artigo procura analisar os significados possíveis das personagens e narrativas. A partir da presença do mito de Medeia, passando pelas releituras da noção de sacrifício até o momento em que a personagem feminina encarna a alegoria da aventura humana em face do fracasso das utopias, o Outro assume a condição de homo faber.