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1.

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.
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2.

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.
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3.

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.
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4.

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.
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5.

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.
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6.

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.
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7.

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.
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8.

Background

Recent studies demonstrate that diverse antidepressant agents increase the cellular production of the nucleolipid CDP-diacylglycerol and its synthetic derivative, phosphatidylinositol, in depression-relevant brain regions. Pharmacological blockade of downstream phosphatidylinositide signaling disrupted the behavioral antidepressant effects in rats. However, the nucleolipid responses were resistant to inhibition by serotonin receptor antagonists, even though antidepressant-facilitated inositol phosphate accumulation was blocked. Could the neurochemical effects be additional to the known effects of the drugs on monoamine transmitter transporters? To examine this question, we tested selected agents in serotonin-depleted brain tissues, in PC12 cells devoid of serotonin transporters, and on the enzymatic activity of brain CDP-diacylglycerol synthase - the enzyme that catalyzes the physiological synthesis of CDP-diacylglycerol.

Results

Imipramine, paroxetine, and maprotiline concentration-dependently increased the levels of CDP-diacylglycerol and phosphatidylinositides in PC12 cells. Rat forebrain tissues depleted of serotonin by pretreatment with p-chlorophenylalanine showed responses to imipramine or maprotiline that were comparable to respective responses from saline-injected controls. With fluoxetine, nucleolipid responses in the serotonin-depleted cortex or hippocampus were significantly reduced, but not abolished. Each drug significantly increased the enzymatic activity of CDP-diacylglycerol synthase following incubations with cortical or hippocampal brain tissues.

Conclusion

Antidepressants probably induce the activity of CDP-diacylglycerol synthase leading to increased production of CDP-diacylglycerol and facilitation of downstream phosphatidylinositol synthesis. Phosphatidylinositol-dependent signaling cascades exert diverse salutary effects in neural cells, including facilitation of BDNF signaling and neurogenesis. Hence, the present findings should strengthen the notion that modulation of brain phosphatidylinositide signaling probably contributes to the molecular mechanism of diverse antidepressant medications.
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9.

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.
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10.

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.
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11.

Background

After unilateral cervical cord lesion at the C7/C8 border interrupting the dorsolateral funiculus in adult monkeys, neutralization of Nogo-A using a specific monoclonal antibody promoted sprouting of corticospinal (CS) axons rostral and caudal to the lesion and, in parallel, improved functional recovery. In monkeys lesioned but not treated with the anti-Nogo-A antibody, the CS neurons in the contralesional primary motor cortex (M1) survived to the axotomy, but their soma shrank. Because the anti-Nogo-A treatment induces regeneration and/or sprouting of CS axons, it may improve access to neurotrophic factors. The question therefore arises as to whether anti-Nogo-A treatment prevents the soma shrinkage observed in the contralesional M1?

Results

Using the marker SMI-32, a quantitative and qualitative anatomical assessment of the pyramidal neurons in the layer V (thus including the CS cells) in M1 was performed and compared across three groups of animals: intact monkeys (n = 5); monkeys subjected to the cervical cord lesion and treated with a control antibody (n = 4); monkeys with the cervical lesion and treated with anti-Nogo-A antibody (n = 5). SMI-32 positive neurons on the side contralateral to the lesion were generally less well stained than those on the ipsilesional hemisphere, suggesting that they expressed less neurofilaments. Nevertheless, in all three groups of monkeys, the amount of SMI-32 positive neurons in both hemispheres was generally comparable, confirming the notion that most axotomized CS neurons survived. However, shrinkage of CS cell body area was observed in the contralesional hemisphere in the two groups of lesioned monkeys. The cell surface shrinkage was found to be of the same magnitude in the monkeys treated with the anti-Nogo-A antibody as in the control antibody treated monkeys.

Conclusion

The anti-Nogo-A antibody treatment did not preserve the axotomized CS cells from soma shrinkage, indicating that the anti-Nogo-A antibody treatment affects morphologically the axotomized CS neurons mainly at distal levels, especially the axon collateralization in the cervical cord, and little or not at all at the level of their soma.
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12.

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.
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13.

Background

How do listeners manage to recognize words in an unfamiliar language? The physical continuity of the signal, in which real silent pauses between words are lacking, makes it a difficult task. However, there are multiple cues that can be exploited to localize word boundaries and to segment the acoustic signal. In the present study, word-stress was manipulated with statistical information and placed in different syllables within trisyllabic nonsense words to explore the result of the combination of the cues in an online word segmentation task.

Results

The behavioral results showed that words were segmented better when stress was placed on the final syllables than when it was placed on the middle or first syllable. The electrophysiological results showed an increase in the amplitude of the P2 component, which seemed to be sensitive to word-stress and its location within words.

Conclusion

The results demonstrated that listeners can integrate specific prosodic and distributional cues when segmenting speech. An ERP component related to word-stress cues was identified: stressed syllables elicited larger amplitudes in the P2 component than unstressed ones.
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14.

Background

Tinnitus is the perception of sound in the absence of any external acoustic stimulation. Transcranial direct current stimulation (tDCS) has shown promising though heterogeneous therapeutic outcomes for tinnitus. The present study aims to review the recent advances in applications of tDCS for tinnitus treatment. In addition, the clinical efficacy and main mechanisms of action of tDCS on suppressing tinnitus are discussed.

Methods

The study was performed in accordance with the PRISMA guidelines. The databases of the PubMed (1980–2018), Embase (1980–2018), PsycINFO (1850–2018), CINAHL, Web of Science, BIOSIS Previews (1990–2018), Cambridge Scientific Abstracts (1990–2018), and google scholar (1980–2018) using the set search terms. The date of the most recent search was 20 May, 2018. The randomized controlled trials that have assessed at least one therapeutic outcome measured before and after tDCS intervention were included in the final analysis.

Results

Different tDCS protocols were used for tinnitus ranging single to repeated sessions (up to 10) consisting of daily single session of 15 to 20-min and current intensities ranging 1–2 mA. Dorsolateral prefrontal cortex (DLPFC) and auditory cortex are the main targets of stimulation. Both single and repeated sessions showed moderate to significant treatment effects on tinnitus symptoms. In addition to improvements in tinnitus symptoms, the tDCS interventions particularly bifrontal DLPFC showed beneficial outcomes on depression and anxiety comorbid with tinnitus. Heterogeneities in the type of tinnitus, tDCS devices, protocols, and site of stimulation made the systematic reviews of the literature difficult. However, the current evidence shows that tDCS can be developed as an adjunct or complementary treatment for intractable tinnitus. TDCS may be a safe and cost-effective treatment for tinnitus in the short-term application.

Conclusions

The current literature shows moderate to significant therapeutic efficacy of tDCS on tinnitus symptoms. Further randomized placebo-controlled double-blind trials with large sample sizes are needed to reach a definitive conclusion on the efficacy of tDCS for tinnitus. Future studies should further focus on developing efficient disease- and patient-specific protocols.
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15.

Background

Peptidergic neurons containing the melanin-concentrating hormone (MCH) and the hypocretins (or orexins) are intermingled in the zona incerta, perifornical nucleus and lateral hypothalamic area. Both types of neurons have been implicated in the integrated regulation of energy homeostasis and body weight. Hypocretin neurons have also been involved in sleep-wake regulation and narcolepsy. We therefore sought to determine whether hypocretin and MCH neurons express Fos in association with enhanced paradoxical sleep (PS or REM sleep) during the rebound following PS deprivation. Next, we compared the effect of MCH and NaCl intracerebroventricular (ICV) administrations on sleep stage quantities to further determine whether MCH neurons play an active role in PS regulation.

Results

Here we show that the MCH but not the hypocretin neurons are strongly active during PS, evidenced through combined hypocretin, MCH, and Fos immunostainings in three groups of rats (PS Control, PS Deprived and PS Recovery rats). Further, we show that ICV administration of MCH induces a dose-dependant increase in PS (up to 200%) and slow wave sleep (up to 70%) quantities.

Conclusion

These results indicate that MCH is a powerful hypnogenic factor. MCH neurons might play a key role in the state of PS via their widespread projections in the central nervous system.
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16.
17.

Background

Previous work suggested that macrophage migration inhibitory factor (MIF) may be involved in bladder inflammation. Therefore, the location of MIF was determined immunohistochemically in the bladder, prostate, major pelvic ganglia, sympathetic chain, the L6-S1 dorsal root ganglia (DRG) and the lumbosacral spinal cord of the rat.

Results

In the pelvic organs, MIF immunostaining was prominent in the epithelia. MIF was widely present in neurons in the MPG and the sympathetic chain. Some of those neurons also co-localized tyrosine hydroxylase (TH). In the DRGs, some of the neurons that stained for MIF also stained for Substance P. In the lumbosacral spinal cord, MIF immunostaining was observed in the white mater, the dorsal horn, the intermediolateral region and in the area around the central canal. Many cells were intensely stained for MIF and glial fibrillary acidic protein (GFAP) suggesting they were glial cells. However, some cells in the lumbosacral dorsal horn were MIF positive, GFAP negative cells suggestive of neurons.

Conclusions

Therefore, MIF, a pro-inflammatory cytokine, is localized to pelvic organs and also in neurons of the peripheral and central nervous tissues that innervate those organs. Changes in MIF's expression at the end organ and at peripheral and central nervous system sites suggest that MIF is involved in pelvic viscera inflammation and may act at several levels to promote inflammatory changes.
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18.

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.
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19.

Background

Low-intensity pulsed ultrasound stimulation (LIPUS) has been proven to be a noninvasive method with high spatial resolution and deep penetration. Previous studies have qualitatively demonstrated that the electromyographic response caused by LIPUS in the mouse motor cortex is affected by the anesthetic state of the mice. However, the quantitative relationship between motor response and anesthetic dose remains unclear.

Results

Experimental results show that the success rate decreases stepwise as the isoflurane concentration/mouse weight ratio increases (ratios: [0.004%/g, 0.01%/g], success rate: ~?90%; [0.012%/g, 0.014%/g], ~?40%; [0.016%/g, 0.018%/g], ~?7%; 0.024%/g, 0). The latency and duration of EMG increase significantly when the ratio is more than 0.016%/g. Compared with that at ratios from 0.004 to 0.016%/g, normalized EMG amplitude decreases significantly at ratios of 0.018%/g and 0.020%/g.

Conclusions

Quantitative calculations indicate that the anesthetic dose has a significant regulatory effect on the motor response of mice during LIPUS. Our results have guiding significance for the selection of the anesthetic dose for LIPUS in mouse motor cortex experiments.
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20.

Background

The clinical significance of anti-neuronal antibodies in patients with psychiatric disorders, but without encephalitis, remains unknown. In patients admitted to acute psychiatric inpatient care we aimed to identify clinical features distinguishing anti-neuronal antibody positive patients from matched controls.

Results

Patients who were serum-positive to N-methyl d-aspartate receptor (NMDAR) (n?=?21), contactin-associated protein 2 (CASPR2) (n?=?14) and/or glutamic acid decarboxylase 65 (GAD65) (n?=?9) antibodies (cases) were age and sex matched (1:2) with serum-negative patients from the same cohort (controls). The prevalence and severity of psychiatric symptoms frequently encountered in NMDAR, CASPR2 and GAD65 antibody associated disorders were compared in cases and controls. NMDAR, CASPR2 and GAD65 antibody positive patients did not differ in their clinical presentation from matched serum negative controls.

Conclusion

In this cohort, patients with and without NMDAR, CASPR2 and GAD65 antibodies admitted to acute psychiatric inpatient care had similar psychiatric phenotypes. This does not exclude their clinical relevance in subgroups of patients, and studies further investigating the clinical significance of anti-neuronal antibodies in patients with psychiatric symptomatology are needed.
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