Neural Correlates of Speech Processing in Prelingually Deafened Children and Adolescents with Cochlear Implants

Prelingually deafened children with cochlear implants stand a good chance of developing satisfactory speech performance. Nevertheless, their eventual language performance is highly variable and not fully explainable by the duration of deafness and hearing experience. In this study, two groups of cochlear implant users (CI groups) with very good basic hearing abilities but non-overlapping speech performance (very good or very bad speech performance) were matched according to hearing age and age at implantation. We assessed whether these CI groups differed with regard to their phoneme discrimination ability and auditory sensory memory capacity, as suggested by earlier studies. These functions were measured behaviorally and with the Mismatch Negativity (MMN). Phoneme discrimination ability was comparable in the CI group of good performers and matched healthy controls, which were both better than the bad performers. Source analyses revealed larger MMN activity (155–225 ms) in good than in bad performers, which was generated in the frontal cortex and positively correlated with measures of working memory. For the bad performers, this was followed by an increased activation of left temporal regions from 225 to 250 ms with a focus on the auditory cortex. These results indicate that the two CI groups developed different auditory speech processing strategies and stress the role of phonological functions of auditory sensory memory and the prefrontal cortex in positively developing speech perception and production.     

网络游戏成瘾的奖赏加工缺陷及其神经机制

奖赏加工异常是网络游戏成瘾（internet gaming disorder，IGD）核心特征之一，近期研究结合认知神经科学技术对IGD的神经机制进行探讨发现，IGD与药物成瘾存在相似的神经基础，但仍然存在较多争议。本文从奖赏类型、奖赏加工阶段梳理了IGD人群奖赏加工的研究进展。IGD人群在游戏相关线索下，奖赏预期（reward anticipation）阶段的奖赏系统激活可能与注意偏向、情绪体验和渴求感增加有关。同时，IGD人群对自然奖赏表现出较为一致的低敏感性，该特征主要出现在结果评估（outcome evaluation）阶段。未来研究可以排除共病因素、结合生动的游戏奖赏刺激，进一步探究奖赏预期和结果评估异常如何推动IGD的发展。     

Amantadine Ameliorates Dopamine-Releasing Deficits and Behavioral Deficits in Rats after Fluid Percussion Injury

Aims

To investigate the role of dopamine in cognitive and motor learning skill deficits after a traumatic brain injury (TBI), we investigated dopamine release and behavioral changes at a series of time points after fluid percussion injury, and explored the potential of amantadine hydrochloride as a chronic treatment to provide behavioral recovery.

Materials and Methods

In this study, we sequentially investigated dopamine release at the striatum and behavioral changes at 1, 2, 4, 6, and 8 weeks after fluid percussion injury. Rats subjected to 6-Pa cerebral cortical fluid percussion injury were treated by using subcutaneous infusion pumps filled with either saline (sham group) or amantadine hydrochloride, with a releasing rate of 3.6mg/kg/hour for 8 weeks. The dopamine-releasing conditions and metabolism were analyzed sequentially by fast scan cyclic voltammetry (FSCV) and high-pressure liquid chromatography (HPLC). Novel object recognition (NOR) and fixed-speed rotarod (FSRR) behavioral tests were used to determine treatment effects on cognitive and motor deficits after injury.

Results

Sequential dopamine-release deficits were revealed in 6-Pa-fluid-percussion cerebral cortical injured animals. The reuptake rate (tau value) of dopamine in injured animals was prolonged, but the tau value became close to the value for the control group after amantadine therapy. Cognitive and motor learning impairments were shown evidenced by the NOR and FSRR behavioral tests after injury. Chronic amantadine therapy reversed dopamine-release deficits, and behavioral impairment after fluid percussion injuries were ameliorated in the rats treated by using amantadine-pumping infusion.

Conclusion

Chronic treatment with amantadine hydrochloride can ameliorate dopamine-release deficits as well as cognitive and motor deficits caused by cerebral fluid-percussion injury.     

Extracellular Matrix in Neural Plasticity and Regeneration

The extracellular matrix (ECM) is a fundamental component of biological tissues. The ECM in the central nervous system (CNS) is unique in both composition and function. Functions such as learning, memory, synaptogenesis, and plasticity are regulated by numerous ECM molecules. The neural ECM acts as a non-specific physical barrier that modulates neuronal plasticity and axon regeneration. There are two specialized types of ECM in the CNS, diffuse perisynaptic ECM and condensed ECM, which selectively surround the perikaryon and initial part of dendritic trees in subtypes of neurons, forming perineuronal nets. This review presents the current knowledge about the role of important neuronal ECM molecules in maintaining the basic functions of a neuron, including electrogenesis and the ability to form neural circuits. The review mainly focuses on the role of ECM components that participate in the control of key events such as cell survival, axonal growth, and synaptic remodeling. Particular attention is drawn to the numerous molecular partners of the main ECM components. These regulatory molecules are integrated into the cell membrane or disposed into the matrix itself in solid or soluble form. The interaction of the main matrix components with molecular partners seems essential in molecular mechanisms controlling neuronal functions. Special attention is paid to the chondroitin sulfate proteoglycan 4, type 1 transmembrane protein, neural-glial antigen 2 (NG2/CSPG4), whose cleaved extracellular domain is such a molecular partner that it not only acts directly on neural and vascular cells, but also exerts its influence indirectly by binding to resident ECM molecules.

     

Neural Adaptation and Behavioral Measures of Temporal Processing and Speech Perception in Cochlear Implant Recipients

The objective was to determine if one of the neural temporal features, neural adaptation, can account for the across-subject variability in behavioral measures of temporal processing and speech perception performance in cochlear implant (CI) recipients. Neural adaptation is the phenomenon in which neural responses are the strongest at the beginning of the stimulus and decline following stimulus repetition (e.g., stimulus trains). It is unclear how this temporal property of neural responses relates to psychophysical measures of temporal processing (e.g., gap detection) or speech perception. The adaptation of the electrical compound action potential (ECAP) was obtained using 1000 pulses per second (pps) biphasic pulse trains presented directly to the electrode. The adaptation of the late auditory evoked potential (LAEP) was obtained using a sequence of 1-kHz tone bursts presented acoustically, through the cochlear implant. Behavioral temporal processing was measured using the Random Gap Detection Test at the most comfortable listening level. Consonant nucleus consonant (CNC) word and AzBio sentences were also tested. The results showed that both ECAP and LAEP display adaptive patterns, with a substantial across-subject variability in the amount of adaptation. No correlations between the amount of neural adaptation and gap detection thresholds (GDTs) or speech perception scores were found. The correlations between the degree of neural adaptation and demographic factors showed that CI users having more LAEP adaptation were likely to be those implanted at a younger age than CI users with less LAEP adaptation. The results suggested that neural adaptation, at least this feature alone, cannot account for the across-subject variability in temporal processing ability in the CI users. However, the finding that the LAEP adaptive pattern was less prominent in the CI group compared to the normal hearing group may suggest the important role of normal adaptation pattern at the cortical level in speech perception.     

Impaired ILK Function Is Associated with Deficits in Hippocampal Based Memory and Synaptic Plasticity in a FASD Rat Model

Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term that encompasses a wide range of anatomical and behavioral problems in children who are exposed to alcohol during the prenatal period. There is no effective treatment for FASD, because of lack of complete characterization of the cellular and molecular mechanisms underlying this condition. Alcohol has been previously characterized to affect integrins and growth factor signaling receptors. Integrin Linked Kinase (ILK) is an effector of integrin and growth-factor signaling which regulates various signaling processes. In FASD, a downstream effector of ILK, Glycogen Synthase Kinase 3β (GSK3β) remains highly active (reduced Ser⁹ phosphorylation). GSK3β has been known to modulate glutamate receptor trafficking and channel properties. Therefore, we hypothesize that the cognitive deficits accompanying FASD are associated with impairments in the ILK signaling pathway. Pregnant Sprague Dawley rats consumed a “moderate” amount of alcohol throughout gestation, or a calorie-equivalent sucrose solution. Contextual fear conditioning was used to evaluate memory performance in 32–33-day-old pups. Synaptic plasticity was assessed in the Schaffer Collateral pathway, and hippocampal protein lysates were used to evaluate ILK signaling. Alcohol exposed pups showed impaired contextual fear conditioning, as compared to control pups. This reduced memory performance was consistent with decrease in LTP as compared to controls. Hippocampal ILK activity and GSK3β Ser^21/9 phosphorylation were significantly lower in alcohol-exposed pups than controls. Increased synaptic expression of GluR2 AMPA receptors was observed with immunoprecipitation of post-synaptic density protein 95 (PSD95). Furthermore, immunoprecipitation of ILK revealed a decreased interaction with GluR2. The ILK pathway appears to play a significant role in memory and synaptic plasticity impairments in FASD rats. These impairments appear to be mediated by reduced GSK3β regulation and increased synaptic stabilization of the calcium-impermeable GluR2 AMPA receptors.     

红景天苷对癫痫大鼠认知功能障碍的治疗作用及其可能机制

目的:探讨红景天苷(Sal)对癫痫大鼠认知功能障碍的治疗作用及其可能机制。方法:将24只成年雄性SD大鼠随机分为健康对照组、模型组、Sal[按体重1g/(kg·d)]干预组。采用Morris水迷宫方法检测大鼠学习记忆功能变化,并检测大鼠脑组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)和谷胱甘肽(GSH)、丙二醛(MDA)相应的比酶活力及含量变化。结果:(1)模型组大鼠寻找平台的潜伏期明显长于对照组,具有统计学意义(P<0.05),Sal组寻找平台的潜伏期相对于模型组显著缩短(P<0.05)。撤离平台后,模型组大鼠在平台所在象限的停留时间明显短于对照组(P<0.05),Sal治疗后大鼠在平台所在象限的停留时间较模型组显著延长(P<0.05)。(2)模型组SOD、GSH、GSH-PX显著下降,MDA明显增高,Sal干预组SOD、GSH、GSH-PX明显增高,而MDA显著下降,有统计学差异(P<0.05)结论:Sal可减轻癫痫持续状态所致的认知功能障碍,其可能机制是通过减轻海马区氧化应激减轻海马区的损伤,进而改善认知功能。     

红景天苷对癫痫大鼠认知功能障碍的治疗作用及其可能机制

目的：探讨红景天苷（sal）对癫痫大鼠认知功能障碍的治疗作用及其可能机制。方法：将24只成年雄性SD大鼠随机分为健康对照组、模型组、Sal[按体重1g／（kg·d）]干预组。采用Morris水迷宫方法检测大鼠学习记忆功能变化,并检测大鼠脑组织中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH—PX）和谷胱甘肽（GSH）、丙二醛（MDA）相应的比酶活力及含量变化。结果：（1）模型组大鼠寻找平台的潜伏期明显长于对照组,具有统计学意义（P〈0．05）,Sal组寻找平台的潜伏期相对于模型组显著缩短（P〈0．05）。撤离平台后,模型组大鼠在平台所在象限的停留时间明显短于对照组（P〈0．05）,sal治疗后大鼠在平台所在象限的停留时间较模型组显著延长（P〈0．05）。（2）模型组SOD、GSH、GSH—Px显著下降,MDA明显增高,Sal干预组SOD、GSH、GSH—PX明显增高．而MDA显著下降,有统计学差异（P〈0．05）。结论：Sal可减轻癫痫持续状态所致的认知功能障碍,其可能机制是通过减轻海马区氧化应激减轻海马区的损伤,进而改善认知功能。     

Synaptic Plasticity in Neural Networks Needs Homeostasis with a Fast Rate Detector

Hebbian changes of excitatory synapses are driven by and further enhance correlations between pre- and postsynaptic activities. Hence, Hebbian plasticity forms a positive feedback loop that can lead to instability in simulated neural networks. To keep activity at healthy, low levels, plasticity must therefore incorporate homeostatic control mechanisms. We find in numerical simulations of recurrent networks with a realistic triplet-based spike-timing-dependent plasticity rule (triplet STDP) that homeostasis has to detect rate changes on a timescale of seconds to minutes to keep the activity stable. We confirm this result in a generic mean-field formulation of network activity and homeostatic plasticity. Our results strongly suggest the existence of a homeostatic regulatory mechanism that reacts to firing rate changes on the order of seconds to minutes.     

Fluorescent-Based Methods for Gene Knockdown and Functional Cardiac Imaging in Zebrafish

A notable advantage of zebrafish as a model organism is the ease of gene knockdown using morpholino antisense oligonucleotide (MO). However, zebrafish morphants injected with MO for a target protein often show heterogeneous phenotypes, despite controlling the injection volume of the MO solution in all embryos. We developed a method for estimating the quantity of MO injected into each living morphant, based on the co-injection of a control MO labeled with the fluorophore lissamine. By applying this method for knockdown of cardiac troponin T (tnnt2a) in zebrafish, we could efficiently select the partial tnnt2a-depleted zebrafish with a decreased heart rate and impairment of cardiac contraction. To investigate cardiac impairment of the tnnt2a morphant, we performed fluorescent cardiac imaging using Bodipy-ceramide. Cardiac image analysis showed moderate reduction of tnnt2a impaired diastolic distensibility and decreased contraction and relaxation velocities. To the best of our knowledge, this is the first report to analyze the role of tnnt2a in cardiac function in tnnt2a-depleted living animals. Our combinatorial approach can be applied for analyzing the molecular function of any protein associated with human cardiac diseases.     

Pretreatment with Resveratrol Prevents Neuronal Injury and Cognitive Deficits Induced by Perinatal Hypoxia-Ischemia in Rats

Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia.     

红景天苷对高原缺氧大鼠认知功能障碍的治疗作用及其可能机制

目的:探讨红景天苷(Sal)对高原缺氧大鼠认知功能障碍的治疗作用及其可能机制。方法:将30只成年雄性SD大鼠随机分为健康对照组、模型组(Model组)、Sal[按体重1g/(kg.d)]治疗组(sal组)。采用Morris水迷宫实验方法检测缺氧后大鼠学习记忆功能变化,同时检测脑组织匀浆中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、谷胱甘肽(GSH)、丙二醛(MDA)的水平。结果:(1)模型组大鼠寻找平台的潜伏期明显长于对照组,具有统计学意义(P<0.05),Sal组寻找平台的潜伏期相对于模型组显著缩短(P<0.05)。撤离平台后,模型组大鼠在平台所在象限的停留时间明显短于对照组(P<0.05),Sal治疗后大鼠在平台所在象限的停留时间较模型组显著延长(P<0.05)。(2)模型组SOD、GSH-PX、GSH显著下降,MDA明显增高,Sal干预组SOD、GSH-PX、GSH显著增高,而MDA明显下降,具有统计学意义(P<0.05)。结论:Sal可改善高原缺氧大鼠认知功能,其可能机制是通过减轻海马区的氧化应激反应减轻海马区的损伤,从而实现改善认知功能。     

红景天苷对高原缺氧大鼠认知功能障碍的治疗作用及其可能机制

目的：探讨红景天苷（Sal）对高原缺氧大鼠认知功能障碍的治疗作用及其可能机制。方法：将30只成年雄性SD大鼠随机分为健康对照组、模型组（Model组）、Sal[按体重1g／（kg·d）]治疗组（sal组）。采用Morris水迷宫实验方法捡测缺氧后大鼠学习记忆功能变化,同时检测脑组织匀浆中超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH—PX）、谷胱甘）lk（GSH）、丙二醛（MDA）的水平。结果：（1）模型组大鼠寻找平台的潜伏期明显长于对照组,具有统计学意义（P〈0．05）,Sal组寻找平台的潜伏期相对于模型组显著缩短（P〈0．05）。撤离平台后,模型组大鼠在平台所在象限的停留时间明显短于对照组（P〈0．05）,Sal治疗后大鼠在平台所在象限的停留时间较模型组显著延长（P〈0．05）。（2）模型组SOD、GSH—PX、GSH显著下降,MDA明显增高,Sal干预组SOD、GSH．PX、GSH显著增高,而MDA明显下降,具有统计学意义（P〈O．05）。结论：Sal可改善高原缺氧大鼠认知功能,其可能机制是通过减轻海马区的氧化应激反应减轻海马区的损伤,从而实现改善认知功能。