On the matching of top-down knowledge with sensory input in the perception of ambiguous speech

Background

How does the brain repair obliterated speech and cope with acoustically ambivalent situations? A widely discussed possibility is to use top-down information for solving the ambiguity problem. In the case of speech, this may lead to a match of bottom-up sensory input with lexical expectations resulting in resonant states which are reflected in the induced gamma-band activity (GBA).

Methods

In the present EEG study, we compared the subject's pre-attentive GBA responses to obliterated speech segments presented after a series of correct words. The words were a minimal pair in German and differed with respect to the degree of specificity of segmental phonological information.

Results

The induced GBA was larger when the expected lexical information was phonologically fully specified compared to the underspecified condition. Thus, the degree of specificity of phonological information in the mental lexicon correlates with the intensity of the matching process of bottom-up sensory input with lexical information.

Conclusions

These results together with those of a behavioural control experiment support the notion of multi-level mechanisms involved in the repair of deficient speech. The delineated alignment of pre-existing knowledge with sensory input is in accordance with recent ideas about the role of internal forward models in speech perception.

     

Effect of visual target blurring on accommodation under distance viewing

Purpose

To examine the effect of visual target blurring on accommodation.

Methods

We evaluated the objective refraction values when the visual target (asterisk; 8°) was changed from the state without Gaussian blur (15 s) to the state with Gaussian blur adapted [0(without blur)?→?10, 0?→?50, 0?→?100: 15 s each].

Results

In Gaussian blur 10, when blurring of the target occurred, refraction value did not change significantly. In Gaussian blur 50 and 100, when blurring of the target occurred, the refraction value became significantly myopic.

Conclusion

Blurring of the distant visual target results in intervention of accommodation.

     

Enhancement of blood-tumor barrier permeability by Sar-[D-Phe8]des-Arg9BK,a metabolically resistant bradykinin B1 agonist,in a rat C6 glioma model

Background

While it is well known that bradykinin B2 agonists increase plasma protein extravasation (PPE) in brain tumors, the bradykinin B1 agonists tested thus far are unable to produce this effect. Here we examine the effect of the selective B1 agonist bradykinin (BK) Sar-[D-Phe8]des-Arg9BK (SAR), a compound resistant to enzymatic degradation with prolonged activity on PPE in the blood circulation in the C6 rat glioma model.

Results

SAR administration significantly enhanced PPE in C6 rat brain glioma compared to saline or BK (p < 0.01). Pre-administration of the bradykinin B1 antagonist [Leu8]-des-Arg (100 nmol/Kg) blocked the SAR-induced PPE in the tumor area.

Conclusions

Our data suggest that the B1 receptor modulates PPE in the blood tumor barrier of C6 glioma. A possible role for the use of SAR in the chemotherapy of gliomas deserves further study.

     

The temporal relationship between reduction of early imitative responses and the development of attention mechanisms

Background

To determine whether early imitative responses fade out following the maturation of attentional mechanisms, the relationship between primitive imitation behaviors and the development of attention was examined in 4-month-old infants. They were divided into high and low imitators, based on an index of imitation. The status of attention was assessed by studying inhibition of return (IOR). Nine-month-old infants were also tested to confirm the hypothesis.

Results

The IOR latency data replicate previous results that infants get faster to produce a covert shift of attention with increasing age. However, those 4-month-olds who showed less imitation had more rapid saccades to the cue before target presentation.

Conclusion

The cortical control of saccade planning appears to be related to an apparent drop in early imitation. We interpret the results as suggesting a relationship between the status of imitation and the neural development of attention-related eye movement.

     

Diverse antidepressants increase CDP-diacylglycerol production and phosphatidylinositide resynthesis in depression-relevant regions of the rat brain

Background  

Major depression is a serious mood disorder affecting millions of adults and children worldwide. While the etiopathology of depression remains obscure, antidepressant medications increase synaptic levels of monoamine neurotransmitters in brain regions associated with the disease. Monoamine transmitters activate multiple signaling cascades some of which have been investigated as potential mediators of depression or antidepressant drug action. However, the diacylglycerol arm of phosphoinositide signaling cascades has not been systematically investigated, even though downstream targets of this cascade have been implicated in depression. With the ultimate goal of uncovering the primary postsynaptic actions that may initiate cellular antidepressive signaling, we have examined the antidepressant-induced production of CDP-diacylglycerol which is both a product of diacylglycerol phosphorylation and a precursor for the synthesis of physiologically critical glycerophospholipids such as the phosphatidylinositides. For this, drug effects on [³H]cytidine-labeled CDP-diacylglycerol and [³H]inositol-labeled phosphatidylinositides were measured in response to the tricyclics desipramine and imipramine, the selective serotonin reuptake inhibitors fluoxetine and paroxetine, the atypical antidepressants maprotiline and nomifensine, and several monoamine oxidase inhibitors.     

Power-law for axon diameters at branch point

Background

Axon calibers vary widely among different animals, neuron classes, and even within the same neuron. What determines the diameter of axon branches?

Results

We pursue the hypothesis that the axon caliber has evolved to minimize signal propagation delays, while keeping arbor volume to a minimum. For a general cost function, we show that the optimal diameters of mother and daughter branches at a bifurcation satisfy a power law. The derivation relies on the fact that the axon conduction speed scales as a power of axon diameter. Although available data are consistent with the law, there is a large spread in the data. Future experimental tests will determine whether this spread is due to biological variability or measurement error.

Conclusions

Minimization of arbor volume and signal propagation delay may have been an important factor in the evolution of the brain.

     

Mathematical modelling and numerical simulation of the morphological development of neurons

Background

The morphological development of neurons is a very complex process involving both genetic and environmental components. Mathematical modelling and numerical simulation are valuable tools in helping us unravel particular aspects of how individual neurons grow their characteristic morphologies and eventually form appropriate networks with each other.

Methods

A variety of mathematical models that consider (1) neurite initiation (2) neurite elongation (3) axon pathfinding, and (4) neurite branching and dendritic shape formation are reviewed. The different mathematical techniques employed are also described.

Results

Some comparison of modelling results with experimental data is made. A critique of different modelling techniques is given, leading to a proposal for a unified modelling environment for models of neuronal development.

Conclusion

A unified mathematical and numerical simulation framework should lead to an expansion of work on models of neuronal development, as has occurred with compartmental models of neuronal electrical activity.

     

PKCε phosphorylation regulates the mitochondrial translocation of ATF2 in ischemia-induced neurodegeneration

Background

Global cerebral ischemia triggers neurodegeneration in the hippocampal CA1 region, but the mechanism of neuronal death remains elusive. The epsilon isoform of protein kinase C (PKCε) has recently been identified as a master switch that controls the nucleocytoplasmic trafficking of ATF2 and the survival of melanoma cells. It is of interest to assess the role of PKCε–ATF2 signaling in neurodegeneration.

Results

Phosphorylation of ATF2 at Thr-52 was reduced in the hippocampus of PKCε null mice, suggesting that ATF2 is a phosphorylation substrate of PKCε. PKCε protein concentrations were significantly reduced 4, 24, 48 and 72 h after transient global cerebral ischemia, resulting in translocation of nuclear ATF2 to the mitochondria. Degenerating neurons staining positively with Fluoro-Jade C exhibited cytoplasmic ATF2.

Conclusions

Our results support the hypothesis that PKCε regulates phosphorylation and nuclear sequestration of ATF2 in hippocampal neurons during ischemia-induced neurodegeneration.

     

Metabolite differences between glutamate carboxypeptidase II gene knockout mice and their wild-type littermates after traumatic brain injury: a 7-tesla <Superscript>1</Superscript>H-MRS study

Background

Traumatic brain injury (TBI) is a complex condition and remains a prominent public and medical health issue in individuals of all ages. A rapid increase in extracellular glutamate occurs after TBI, leading to glutamate-induced excitotoxicity, which causes neuronal damage and further functional impairments. Although inhibition of glutamate carboxypeptidase II (GCP II) is considered a potential approach for reducing glutamate-induced excitotoxicity after TBI, further detailed evidence regarding its efficacy is required. Therefore, in this study, we examined the differences in the metabolite status between wild-type (WT) and GCP II gene-knockout (KO) mice after TBI using proton magnetic resonance spectroscopy (1H-MRS) and T2-weighted magnetic resonance (MR) imaging with a 7-tesla imaging system, and brain water-content analysis.

Results

Evaluation of glutamate and N-acetylaspartate concentrations revealed a decrease in both levels in the ipsilateral hippocampus at 24 h post-TBI; however, the reduction in glutamate and N-acetylaspartate levels was less marked in GCP II-KO mice than in WT mice (p?<?0.05). T2 MR data and brain water-content analysis demonstrated that the extent of cortical edema and brain swelling was less in KO than in WT mice after TBI (p?<?0.05).

Conclusion

Using two non-invasive methods, 1H-MRS and T2 MR imaging, as well as in vitro brain-water content measurements, we demonstrated that the mechanism underlying the neuroprotective effects of GCP II-KO against brain swelling in TBI involves changes in glutamate and N-acetylaspartate levels. This knowledge may contribute towards the development of therapeutic strategies for TBI.

     

Altered <Emphasis Type="Italic">Slc25</Emphasis> family gene expression as markers of mitochondrial dysfunction in brain regions under experimental mixed anxiety/depression-like disorder

Background

Development of anxiety- and depression-like states under chronic social defeat stress in mice has been shown by many experimental studies. In this article, the differentially expressed Slc25* family genes encoding mitochondrial carrier proteins were analyzed in the brain of depressive (defeated) mice versus aggressive mice winning in everyday social confrontations. The collected samples of brain regions were sequenced at JSC Genoanalytica (http://genoanalytica.ru/, Moscow, Russia).

Results

Changes in the expression of the 20 Slc25* genes in the male mice were brain region- and social experience (positive or negative)-specific. In particular, most Slc25* genes were up-regulated in the hypothalamus of defeated and aggressive mice and in the hippocampus of defeated mice. In the striatum of defeated mice and in the ventral tegmental area of aggressive mice expression of mitochondrial transporter genes changed specifically. Significant correlations between expression of most Slc25* genes and mitochondrial Mrps and Mrpl genes were found in the brain regions.

Conclusion

Altered expression of the Slc25* genes may serve as a marker of mitochondrial dysfunction in brain, which accompanies the development of many neurological and psychoemotional disorders.

     

Relationship between corneal and ocular higher order wavefront aberrations and age in children

Purpose

To evaluate the relationship between corneal and ocular higher order wavefront aberrations (HOAs) and age in young subjects aged 20 years or less.

Methods

Corneal and ocular HOAs of the right eyes of 87 normal subjects were measured using videokeratography and the Hartmann–Shack wavefront aberrometer (KR-9000PW; Topcon Corp., Tokyo, Japan). The HOAs were calculated using Zernike polynomials up to the sixth order. From the Zernike coefficients, the root mean squares (RMS) of coma and spherical aberration were calculated.

Results

Corneal spherical-like aberrations significantly correlated with age (r = 0.420, p < 0.001); however, coma-like aberrations and total HOAs did not significantly correlate with age. None of the ocular HOAs significantly correlated with age. In addition, a gender-wise comparison of the collected data showed that corneal and ocular HOAs did not significantly correlate with age.

Conclusion

In children, the corneal and ocular total HOAs did not vary with age. Compared to the previous reports in adults, we found fewer corneal and ocular HOAs in children.

     

Comparison of the responses of the chorda tympani and glossopharyngeal nerves to taste stimuli in C57BL/6J mice

Background

Recent progress in discernment of molecular pathways of taste transduction underscores the need for comprehensive phenotypic information for the understanding of the influence of genetic factors in taste. To obtain information that can be used as a base line for assessment of effects of genetic manipulations in mice taste, we have recorded the whole-nerve integrated responses to a wide array of taste stimuli in the chorda tympani (CT) and glossopharyngeal (NG) nerves, the two major taste nerves from the tongue.

Results

In C57BL/6J mice the responses in the two nerves were not the same. In general sweeteners gave larger responses in the CT than in the NG, while responses to bitter taste in the NG were larger. Thus the CT responses to cyanosuosan, fructose, NC00174, D-phenylalanline and sucrose at all concentrations were significantly larger than in the NG, whereas for acesulfame-K, L-proline, saccharin and SC45647 the differences were not significant. Among bitter compounds amiloride, atropine, cycloheximide, denatonium benzoate, L-phenylalanine, 6-n-propyl-2-thiouracil (PROP) and tetraethyl ammonium chloride (TEA) gave larger responses in the NG, while the responses to brucine, chloroquine, quinacrine, quinine hydrochloride (QHCl), sparteine and strychnine, known to be very bitter to humans, were not significantly larger in the NG than in the CT.

Conclusion

These data provide a comprehensive survey and comparison of the taste sensitivity of the normal C57BL/6J mouse against which the effects of manipulations of its gustatory system can be better assessed.

     

Mapping the brain's orchestration during speech comprehension: task-specific facilitation of regional synchrony in neural networks

Background

How does the brain convert sounds and phonemes into comprehensible speech? In the present magnetoencephalographic study we examined the hypothesis that the coherence of electromagnetic oscillatory activity within and across brain areas indicates neurophysiological processes linked to speech comprehension.

Results

Amplitude-modulated (sinusoidal 41.5 Hz) auditory verbal and nonverbal stimuli served to drive steady-state oscillations in neural networks involved in speech comprehension. Stimuli were presented to 12 subjects in the following conditions (a) an incomprehensible string of words, (b) the same string of words after being introduced as a comprehensible sentence by proper articulation, and (c) nonverbal stimulations that included a 600-Hz tone, a scale, and a melody. Coherence, defined as correlated activation of magnetic steady state fields across brain areas and measured as simultaneous activation of current dipoles in source space (Minimum-Norm-Estimates), increased within left- temporal-posterior areas when the sound string was perceived as a comprehensible sentence. Intra-hemispheric coherence was larger within the left than the right hemisphere for the sentence (condition (b) relative to all other conditions), and tended to be larger within the right than the left hemisphere for nonverbal stimuli (condition (c), tone and melody relative to the other conditions), leading to a more pronounced hemispheric asymmetry for nonverbal than verbal material.

Conclusions

We conclude that coherent neuronal network activity may index encoding of verbal information on the sentence level and can be used as a tool to investigate auditory speech comprehension.

     

Qualitative and quantitative differences between taste buds of the rat and mouse

Background

Numerous electrophysiological, ultrastructural, and immunocytochemical studies on rodent taste buds have been carried out on rat taste buds. In recent years, however, the mouse has become the species of choice for molecular and other studies on sensory transduction in taste buds. Do rat and mouse taste buds have the same cell types, sensory transduction markers and synaptic proteins? In the present study we have used antisera directed against PLCβ2, α-gustducin, serotonin (5-HT), PGP 9.5 and synaptobrevin-2 to determine the percentages of taste cells expressing these markers in taste buds in both rodent species. We also determined the numbers of taste cells in the taste buds as well as taste bud volume.

Results

There are significant differences (p < 0.05) between mouse and rat taste buds in the percentages of taste cells displaying immunoreactivity for all five markers. Rat taste buds display significantly more immunoreactivity than mice for PLCβ2 (31.8% vs 19.6%), α-gustducin (18% vs 14.6%), and synaptobrevin-2 (31.2% vs 26.3%). Mice, however, have more cells that display immunoreactivity to 5-HT (15.9% vs 13.7%) and PGP 9.5 (14.3% vs 9.4%). Mouse taste buds contain an average of 85.8 taste cells vs 68.4 taste cells in rat taste buds. The average volume of a mouse taste bud (42,000 μm³) is smaller than a rat taste bud (64,200 μm³). The numerical density of taste cells in mouse circumvallate taste buds (2.1 cells/1000 μm³) is significantly higher than that in the rat (1.2 cells/1000 μm³).

Conclusion

These results suggest that rats and mice differ significantly in the percentages of taste cells expressing signaling molecules. We speculate that these observed dissimilarities may reflect differences in their gustatory processing.

     

Measuring information integration

Background

To understand the functioning of distributed networks such as the brain, it is important to characterize their ability to integrate information. The paper considers a measure based on effective information, a quantity capturing all causal interactions that can occur between two parts of a system.

Results

The capacity to integrate information, or Φ, is given by the minimum amount of effective information that can be exchanged between two complementary parts of a subset. It is shown that this measure can be used to identify the subsets of a system that can integrate information, or complexes. The analysis is applied to idealized neural systems that differ in the organization of their connections. The results indicate that Φ is maximized by having each element develop a different connection pattern with the rest of the complex (functional specialization) while ensuring that a large amount of information can be exchanged across any bipartition of the network (functional integration).

Conclusion

Based on this analysis, the connectional organization of certain neural architectures, such as the thalamocortical system, are well suited to information integration, while that of others, such as the cerebellum, are not, with significant functional consequences. The proposed analysis of information integration should be applicable to other systems and networks.

     

Relationship between central and peripheral corneal astigmatism in elderly patients

Purpose

We investigated the relationship between central and peripheral corneal astigmatism in elderly patients.

Methods

Seventy-six eyes of 76 elderly subjects (mean age?=?72.6?±?3.0 years) were included in the study. Corneal shape was evaluated using the Pentacam HR (Oculus, Wetzlark, Germany), which is comprised of a rotating Scheimpflug camera and a short-wavelength slit light. The power distribution map was selected and corneal astigmatism was calculated using front K-Readings in zones centered on the pupil. Analyzed zones were 2.0–6.0 mm in diameter.

Results

Corneal astigmatism decreased as diameter increased, similar to what was observed in eyes with with-the-rule astigmatism and against-the-rule astigmatism (ANOVA, p?<?0.01). This effect was more pronounced in eyes with a large central corneal astigmatism (Spearman’s rank-correlation coefficient test, r?=?0.51, p?<?0.01). There was no change as to axis of corneal astigmatism (ANOVA, p?=?0.98).

Conclusion

These results suggest that the relationship between central and peripheral corneal astigmatism should be taken into consideration to optimize vision when astigmatic correction is needed.

     

Learning course adjustments during arm movements with reversed sensitivity derivatives

Background

To learn, a motor system needs to know its sensitivity derivatives, which quantify how its neural commands affect motor error. But are these derivatives themselves learned, or are they known solely innately? Here we test a recent theory that the brain's estimates of sensitivity derivatives are revisable based on sensory feedback. In its simplest form, the theory says that each control system has a single, adjustable estimate of its sensitivity derivatives which affects all aspects of its task, e.g. if you learn to reach to mirror-reversed targets then your revised estimate should reverse not only your initial aiming but also your online course adjustments when the target jumps in mid-movement.

Methods

Human subjects bent a joystick to move a cursor to a target on a computer screen, but the cursor's motion was reversed relative to the joystick's. The target jumped once during each movement. Subjects had up to 4000 trials to practice aiming and responding to target jumps.

Results

All subjects learned to reverse both initial aiming and course adjustments.

Conclusions

Our study confirms that sensitivity derivatives can be relearned. It is consistent with the idea of a single, all-purpose estimate of those derivatives; and it suggests that the estimate is a function of context, as one would expect given that the true sensitivity derivatives may vary with the state of the controlled system, the target, and the motor commands.

     

Topography-specific spindle frequency changes in Obstructive Sleep Apnea

Background

Sleep spindles, as detected on scalp electroencephalography (EEG), are considered to be markers of thalamo-cortical network integrity. Since obstructive sleep apnea (OSA) is a known cause of brain dysfunction, the aim of this study was to investigate sleep spindle frequency distribution in OSA. Seven non-OSA subjects and 21 patients with OSA (11 mild and 10 moderate) were studied. A matching pursuit procedure was used for automatic detection of fast (≥13Hz) and slow (<13Hz) spindles obtained from 30min samples of NREM sleep stage 2 taken from initial, middle and final night thirds (sections I, II and III) of frontal, central and parietal scalp regions.

Results

Compared to non-OSA subjects, Moderate OSA patients had higher central and parietal slow spindle percentage (SSP) in all night sections studied, and higher frontal SSP in sections II and III. As the night progressed, there was a reduction in central and parietal SSP, while frontal SSP remained high. Frontal slow spindle percentage in night section III predicted OSA with good accuracy, with OSA likelihood increased by 12.1%for every SSP unit increase (OR 1.121, 95% CI 1.013 - 1.239, p=0.027).

Conclusions

These results are consistent with diffuse, predominantly frontal thalamo-cortical dysfunction during sleep in OSA, as more posterior brain regions appear to maintain some physiological spindle frequency modulation across the night. Displaying changes in an opposite direction to what is expected from the aging process itself, spindle frequency appears to be informative in OSA even with small sample sizes, and to represent a sensitive electrophysiological marker of brain dysfunction in OSA.