磁场对小鼠两种迷宫学习记忆的影响

据发现,磁场对生物体有一定作用,但是磁场对于人类或实验动物的学习记忆是否有影响,目前的报道结果很不一致。本实验采用实验小白鼠,给予不同强度（65高斯／50Hz,35高斯/25Hz）的低频磁场照射（每天1小时,持续25天）。磁场照射后,采用旷场行为测试、Y-迷宫和Morris水迷宫,检测小鼠的活动性、空间辨别、空间学习记忆和非空间学习记忆能力。结果表明：65高斯／50Hz磁场显著增高小鼠的活动性,并损伤小鼠Y-迷宫的空间辨别能力,但对Morris水迷宫的空间、非空间学习记忆无明显影响。35高斯／25Hz磁场处理动物行为在三个指标上均接近对照组。提示：长期的磁场照射可能会给动物,甚至人类造成一些影响。     

Single, brief exposure to a 50 Hz magnetic field does not affect the performance of an object recognition task in adult mice

A number of studies have shown that power frequency magnetic fields may affect spatial memory functions in rodents. An experiment was performed using a spontaneous object recognition task to investigate if nonspatial working memory was similarly affected. Memory changes in adult, male C57BL/6J mice were assessed by measuring the relative time within which the animals explored familiar or novel stimulus objects. Between initial testing and retesting, the animals were exposed for 45 min to a 50 Hz magnetic field at either 7.5 microT, 75 microT or 0.75 mT. Other animals were sham-exposed with ambient fields of less than 50 nT. No significant field-dependent effects on the performance of the task were observed at any flux density (for all measures, P > 0.05). These data provide no evidence to suggest that nonspatial working memory was affected in mice by acute exposure to an intense 50 Hz magnetic field.     

Behavioral effects of [4-norleucine, 7-D-phenylalanine]-alpha-melanocyte-stimulating hormone

The behavioral effects of alpha-melanocyte stimulating hormone (alpha-MSH) were compared to an alpha-MSH analogue that had a norleucine substituted for methionine in the four position and a D-phenylalanine substituted for L-phenylalanine in the seven position. [Nle4, D-Phe7]-alpha-MSH has previously been shown to be a superpotent agonist on melanocytes [17]. The present experiments indicate that [Nle4, D-Phe7]-alpha-MSH is equipotent to alpha-MSH in inducing grooming when administered intraventricularly. In contrast, the analogue has the opposite effect of alpha-MSH on performance of a visual discrimination task. alpha-MSH improves visual performance whereas [Nle4, D-Phe7]-alpha-MSH attenuates such performance. The contrasting activities of [Nle4, D-Phe7]-alpha-MSH on the physiological processes described suggest that this analogue may interact with three distinct melanotropin receptors in different ways. On melanocyte receptors the melanotropin analogue is a superagonist, on CNS melanotropin receptors involved in grooming it is equipotent to alpha-MSH, and on CNS receptors involved in attention, learning and memory [Nle4, D-Phe7]-alpha-MSH may be an antagonist of endogenous melanotropin.     

Genetic variation of the serotonin 2a receptor affects hippocampal novelty processing in humans

Serotonin (5-hydroxytryptamine, 5-HT) is an important neuromodulator in learning and memory processes. A functional genetic polymorphism of the 5-HT 2a receptor (5-HTR2a His452Tyr), which leads to blunted intracellular signaling, has previously been associated with explicit memory performance in several independent cohorts, but the underlying neural mechanisms are thus far unclear. The human hippocampus plays a critical role in memory, particularly in the detection and encoding of novel information. Here we investigated the relationship of 5-HTR2a His452Tyr and hippocampal novelty processing in 41 young, healthy subjects using functional magnetic resonance imaging (fMRI). Participants performed a novelty/familiarity task with complex scene stimuli, which was followed by a delayed recognition memory test 24 hours later. Compared to His homozygotes, Tyr carriers exhibited a diminished hippocampal response to novel stimuli and a higher tendency to judge novel stimuli as familiar during delayed recognition. Across the cohort, the false alarm rate during delayed recognition correlated negatively with the hippocampal novelty response. Our results suggest that previously reported effects of 5-HTR2a on explicit memory performance may, at least in part, be mediated by alterations of hippocampal novelty processing.     

Cognitive effects of head-movements in stray fields generated by a 7 Tesla whole-body MRI magnet

The study investigates the impact of exposure to the stray magnetic field of a whole-body 7 T MRI scanner on neurobehavioral performance and cognition. Twenty seven volunteers completed four sessions, which exposed them to approximately 1600 mT (twice), 800 mT and negligible static field exposure. The order of exposure was assigned at random and was masked by placing volunteers in a tent to hide their position relative to the magnet bore. Volunteers completed a test battery assessing auditory working memory, eye-hand co-ordination, and visual perception. During three sessions the volunteers were instructed to complete a series of standardized head movements to generate additional time-varying fields ( approximately 300 and approximately 150 mT.s(-1) r.m.s.). In one session, volunteers were instructed to keep their heads as stable as possible. Performance on a visual tracking task was negatively influenced (P<.01) by 1.3% per 100 mT exposure. Furthermore, there was a trend for performance on two cognitive-motor tests to be decreased (P<.10). No effects were observed on working memory. Taken together with results of earlier studies, these results suggest that there are effects on visual perception and hand-eye co-ordination, but these are weak and variable between studies. The magnitude of these effects may depend on the magnitude of time-varying fields and not so much on the static field. While this study did not include exposure above 1.6 T, it suggests that use of strong magnetic fields is not a significant confounder in fMRI studies of cognitive function. Future work should further assess whether ultra-high field may impair performance of employees working in the vicinity of these magnets.     

Acute effects of 50 Hz, 100 μT magnetic field exposure on visual duration discrimination at two different times of the day

A two-alternative, forced-choice visual duration discrimination task was used to examine the effect of an intermittent, 50 Hz, 100 μT magnetic field on accuracy at two different times of the day. A total of 59 female and 40 male subjects with an age range of 18 to 46 years were studied under both field-exposed and sham-exposed conditions. The subject's task was to decide which of two sequentially presented light flashes had the longer duration, percentage correct being the measure of performance. The data were gathered under double-blind conditions with sham and real exposure counterbalanced. Exposure to the magnetic field produced a small improvement in accuracy but only at the most difficult level of the task, with female subjects showing a larger improvement than males. The time of day at which the study was run had no effect on performance. Despite the relatively large number of subjects used and a relaxed alpha level (P = .3), the statistical power of the test to detect the observed effect was still only 0.71. Bioelectromagnetics 19:310–317, 1998. © 1998 Wiley-Liss, Inc.     

Specific timing of taurine supplementation affects learning ability in mice

The effects of taurine supplementation on visual discrimination in mice were examined. Taurine, 2-aminoethane-sulphonic acid, found in high concentrations in the central nervous system of mammals and in human milk, has been shown to be essential for development. Male mice were divided into four groups according to taurine supplementation periods. 1) Lifelong: taurine (400 mg/kg/day) was dissolved in distilled water and provided as drinking water. In the prenatal period, taurine was given via the mother. After weaning mice were administered taurine in drinking water. 2) Pre-weaning: mice were exposed to taurine prior to weaning, 3) Post-weaning: mice were exposed to taurine after weaning. 4) Control: no supplementation of taurine. It was shown that the Lifelong group required a longer period of time to acquire visual discrimination than the Control group. Conversely, in the Post-weaning group, mice learned the task faster than Controls. Visual discrimination learning time in the Pre-weaning group showed no significant difference compared with that in the Control group. From these results, we suggest that the perinatal to early postnatal period is a “sensitive period” where taurine supplementation can result in retardation of learning in later life. At the same time, taurine supplementation after weaning improved visual discrimination learning. Thus, timing of taurine supplementation affected learning.     

A replication study of human exposure to 60-Hz fields: effects on neurobehavioral measures.

The purpose of this study was to reproduce and extend an earlier investigation of the effects of human exposure to combined, 60-Hz electric and magnetic fields. This paper presents the neurobehavioral results. Thirty men participated in one training session and four testing sessions. Subjects were randomly assigned to two groups. The 18 subjects in Group I were exposed (9 kV/m, 20 microT) and sham exposed in two counterbalanced orders. In Group II, half of 12 subjects were exposed (9 kV/m, 20 microT) every session, and the remaining half were sham exposed every session. The study was doubly blinded. Measures of cardiac interbeat interval, event-related brain potentials, and performance were obtained before, during, and after exposures. As in the earlier study, exposure to the combined field resulted in a statistically significant slowing of heart rate, in changes in late components of event-related brain potentials, and in decreased errors on a choice reaction-time task. In addition, field effects on several other measures approached statistical significance. The physiological measures obtained during exposure indicated that effects were greatest soon after the field was switched on, and again when it was switched off. The data indicate that changes in exposure level may be more important than duration of exposure for producing effects in human beings.     

Modulation of activity in human visual area V1 during memory masking

Neurons in the primary visual cortex, V1, are specialized for the processing of elemental features of the visual stimulus, such as orientation and spatial frequency. Recent fMRI evidence suggest that V1 neurons are also recruited in visual perceptual memory; a number of studies using multi-voxel pattern analysis have successfully decoded stimulus-specific information from V1 activity patterns during the delay phase in memory tasks. However, consistent fMRI signal modulations reflecting the memory process have not yet been demonstrated. Here, we report evidence, from three subjects, that the low V1 BOLD activity during retention of low-level visual features is caused by competing interactions between neural populations coding for different values along the spectrum of the dimension remembered. We applied a memory masking paradigm in which the memory representation of a masker stimulus interferes with a delayed spatial frequency discrimination task when its frequency differs from the discriminanda with ±1 octave and found that impaired behavioral performance due to masking is reflected in weaker V1 BOLD signals. This cross-channel inhibition in V1 only occurs with retinotopic overlap between the masker and the sample stimulus of the discrimination task. The results suggest that memory for spatial frequency is a local process in the retinotopically organized visual cortex.     

与作业无关的新异刺激对猕猴额叶神经元延缓期反应的作用

在猕猴执行延缓辨别作业和单纯辨别作业时,观察了与作业无关的新异刺激对额叶神经元延缓期放电的影响。在这两种作业中,延缓期在1—4s之间随机变化。此时,动物必须高度注意信号的变化,稍不注意即导致操作错误。此外,在延缓辨别作业中,动物在延缓期还要暂时记住暗示期的信号,单纯辨别作业则无此要求。在203个与作业相关的神经元中,有70个神经元在延缓期出现放电频率变化,其中见于延缓辨别作业者41个,见于单纯辨别作业者29个。实验结果表明,在这两种作业的延缓期所出现的神经元放电增多的反应,有着许多相同的特点。与课题无关的声、光、触、痛等刺激引起分心时,神经元的延缓期反应出现明显的变化,随之出现操作错误。多数神经元的反应受到抑制,但也有出现反应增强者,而且同一神经元对不同感觉模式的无关刺激可出现不同的效应,表现出不同程度的感觉模式特异性。此外,无关刺激在延缓期和在测试间歇期可产生不同甚至相反的效应。上述在延缓期出现反应的神经元主要位于额叶弓状沟上支内侧部的一定范围内。本文对实验结果进行了讨论,认为额叶神经元的延缓期反应,可能在很大程度上与注意有关。额叶神经元感觉模式各种程度的特异性可能是注意的通道选择性的神经基础。额叶的背内侧部,包括前额叶后部和运动前区前部     

Galanthamine plus estradiol treatment enhances cognitive performance in aged ovariectomized rats

We hypothesize that beneficial effects of estradiol on cognitive performance diminish with age and time following menopause due to a progressive decline in basal forebrain cholinergic function. This study tested whether galanthamine, a cholinesterase inhibitor used to treat memory impairment associated with Alzheimer's disease, could enhance or restore estradiol effects on cognitive performance in aged rats that had been ovariectomized in middle-age. Rats were ovariectomized at 16–17 months of age. At 21–22 months of age rats began receiving daily injections of galanthamine (5 mg/day) or vehicle. After one week, half of each group also received 17ß-estradiol administered subcutaneously. Rats were then trained on a delayed matching to position (DMP) T-maze task, followed by an operant stimulus discrimination/reversal learning task. Treatment with galanthamine + estradiol significantly enhanced the rate of DMP acquisition and improved short-term delay-dependent spatial memory performance. Treatment with galanthamine or estradiol alone was without significant effect. Effects were task-specific in that galanthamine + estradiol treatment did not significantly improve performance on the stimulus discrimination/reversal learning task. In fact, estradiol was associated with a significant increase in incorrect responses on this task after reversal of the stimulus contingency. In addition, treatments did not significantly affect hippocampal choline acetyltransferase activity or acetylcholine release. This may be an effect of age, or possibly is related to compensatory changes associated with long-term cholinesterase inhibitor treatment. The data suggest that treating with a cholinesterase inhibitor can enhance the effects of estradiol on acquisition of a DMP task by old rats following a long period of hormone deprivation. This could be of particular benefit to older women who have not used hormone therapy for many years and are beginning to show signs of mild cognitive impairment. Potential mechanisms for these effects are discussed.     

去甲肾上腺素对猕猴额叶延缓辨别作业相关神经元活动的效应

为了研究去甲肾上腺素在大脑认知功能中的作用,在3只猕猴进行延缓辨别作业的同时,在额叶弓状沟上支内侧部的皮层区,记录了230个作业相关神经元的电活动。对其中159个神经元观察了微量电泳去甲肾上腺素、妥拉苏林或心得安的效应。这些神经元在作业各期的分布是:开始期11个,暗示期28个,延缓期66个,反应期54个。约2/3的神经元在作业中出现兴奋反应(放电增多),1/3为抑制反应(放电减少)。在延缓期出现抑制反应的神经元,绝大多数对去甲肾上腺素敏感。在电泳去甲肾上腺素时,神经元的自发放电减少,延缓期的抑制加深。电泳妥拉苏林或心得安则出现相反的效应,即自发放电增多,延缓期的抑制减弱或不出现抑制,并可拮抗电泳去甲肾上腺素的抑制效应。实验结果提示,在额叶弓状沟上支内侧皮层神经元的注意、短时记忆等认知功能中,可能有去甲肾上腺素参与作用,主要参与神经活动的抑制过程。     

Effects of atropine on operant test battery performance in rhesus monkeys.

The acute behavioral effects of atropine sulfate were assessed using a battery of complex food-reinforced operant tasks that included: temporal response differentiation (TRD, n = 7); delayed matching-to-sample (DMTS, n = 6), progressive ratio (PR, n = 8), incremental repeated acquisition (IRA, n = 8), and conditioned position responding (CPR, n = 8). Performance in these tasks is thought to depend primarily upon specific brain functions such as time perception, short-term memory and attention, motivation, learning, and color and position discrimination, respectively. Atropine sulfate (0.01-0.56 mg/kg iv), given 15-min pretesting, produced significant dose-dependent decreases in the number of reinforcers obtained in all tasks. Response rates decreased significantly at greater than or equal to 0.03 mg/kg for the learning and discrimination tasks, at greater than or equal to 0.10 mg/kg for the motivation and short-term memory and attention tasks, and at greater than or equal to 0.30 mg/kg for the time perception task. Response accuracies were significantly decreased at doses greater than or equal to 0.10 mg/kg for the learning, discrimination, and short-term memory and attention tasks, and at greater than or equal to 0.30 mg/kg for the time perception task. Thus, the order of task sensitivity to any disruption by atropine is learning = color and position discrimination greater than time perception = short-term memory and attention = motivation (IRA = CPR greater than TRD = DMTS = PR). Thus in monkeys, the rates of responding in operant tasks designed to model learning and color and position discrimination were the most sensitive measures to atropine's behavioral effects. Accuracy in these same task was also disrupted but at higher doses. These data support the hypothesis that cholinergic systems play a greater role in the speed (but not accuracy) of performance of our learning and discrimination tasks compared to all other tasks. Accuracy of responding in these and the short-term memory task, all of which involve the use of lights as visual stimuli, was more sensitive to disruption by atropine than those tasks which did not utilize such strong visual stimuli.     

Intrusiefouten bij geheugenonderzoek

Extra-list intrusion errors during five trials of the eight-word list-learning task of the Amsterdam Dementia Screening Test (ADST) were investigated in 823 consecutive psychogeriatric patients (87.1% suffering from major neurocognitive disorder). Almost half of the participants (45.9%) produced one or more intrusion errors on the verbal recall test. Correct responses were lower when subjects made intrusion errors, but learning slopes did not differ between subjects who committed intrusion errors and those who did not so. Bivariate regression analyses revealed that participants who committed intrusion errors were more deficient on measures of eight-word recognition memory, delayed visual recognition and tests of executive control (the Behavioral Dyscontrol Scale and the ADST-Graphical Sequences as measures of response inhibition). Using hierarchical multiple regression, only free recall and delayed visual recognition retained an independent effect in the association with intrusion errors, such that deficient scores on tests of episodic memory were sufficient to explain the occurrence of intrusion errors. Measures of inhibitory control did not add significantly to the explanation of intrusion errors in free recall, which makes insufficient strength of memory traces rather than a primary deficit in inhibition the preferred account for intrusion errors in free recall.     

Dorsoventral asymmetry of colour discrimination in bees

Colour discrimination performance of honeybees was examined by training bees to a two-coloured disc presented on a vertical plane. Access to the food reward was through the centre of the disc. In one experiment, the upper half of the disc was yellow, and the lower half blue. In another experiment, this was vice versa. In either case, the learned disc was tested against each of a series of ten discs whose colour differed in either the upper or the lower half. A comparison between the results obtained in the two experiments reveals that colour discrimination is significantly better in the lower half of the frontal eye region than it is in the upper half. The results, similar to earlier results obtained in pattern discrimination tasks, cannot be explained by peripheral eye-region-specific specializations. It is proposed that the functional significance of the lower frontal visual field is based on more central neural mechanisms that might constitute an adaptation to the forager's natural needs. Accepted: 2 November 1998     

Improved Discrimination of Visual Stimuli Following Repetitive Transcranial Magnetic Stimulation

Background

Repetitive transcranial magnetic stimulation (rTMS) at certain frequencies increases thresholds for motor-evoked potentials and phosphenes following stimulation of cortex. Consequently rTMS is often assumed to introduce a “virtual lesion” in stimulated brain regions, with correspondingly diminished behavioral performance.

Methodology/Principal Findings

Here we investigated the effects of rTMS to visual cortex on subjects'' ability to perform visual psychophysical tasks. Contrary to expectations of a visual deficit, we find that rTMS often improves the discrimination of visual features. For coarse orientation tasks, discrimination of a static stimulus improved consistently following theta-burst stimulation of the occipital lobe. Using a reaction-time task, we found that these improvements occurred throughout the visual field and lasted beyond one hour post-rTMS. Low-frequency (1 Hz) stimulation yielded similar improvements. In contrast, we did not find consistent effects of rTMS on performance in a fine orientation discrimination task.

Conclusions/Significance

Overall our results suggest that rTMS generally improves or has no effect on visual acuity, with the nature of the effect depending on the type of stimulation and the task. We interpret our results in the context of an ideal-observer model of visual perception.     

Intact performance on feature-ambiguous discriminations in rats with lesions of the perirhinal cortex

We developed a behavioral paradigm for the rat that made it possible to separate the evaluation of memory functions from the evaluation of perceptual functions. Animals were given extensive training on an automated two-choice discrimination task and then maintained their memory performance at a high level while interpolated probe trials tested visual perceptual ability. The probe trials systematically varied the degree of feature ambiguity between the stimuli, such that perceptual functions could be tested across 14 different levels of difficulty. As feature ambiguity increased, performance declined in an orderly, monotonic manner (from 87% correct to chance, 50% correct). Bilateral lesions of the perirhinal cortex fully spared the capacity to make feature-ambiguous discriminations and the performance of lesioned and intact animals was indistinguishable at every difficulty level. In contrast, the perirhinal lesions did impair recognition memory. The findings suggest that the perirhinal cortex is important for memory and not for perceptual functions.     

Effects of extremely low‐frequency magnetic field exposure on cognitive functions: results of a meta‐analysis

There is extensive literature on possible effects of extremely low‐frequency magnetic fields (ELF‐MFs) on human cognitive functions. However, due to methodological deficits (e.g., low statistical power, small sample sizes) findings have been inconsistent. In the current study we try to overcome these problems by carrying out a meta‐analysis. Literature research revealed 17 studies. Nine of these were included in the meta‐analysis because they fulfilled minimum requirements (e.g., at least single‐blind experimental study design and documentation of means and standard deviation of the dependent variables). All of the studies used a 50 Hz magnetic field exposure. Small but significant effect sizes could be detected in two cognitive dimensions: in the hard level of visual duration discrimination, task‐exposed subjects performed better than controls; at the intermediate level however, exposed subjects performed worse. Additionally, a significant improvement of correct responses was observed in the dimension of “flexibility” under exposure. However, due to the small number of studies per performance dimensions and the resulting instability of estimates, these findings have to be treated with extreme caution. Taken together, the results of the meta‐analysis provide little evidence that ELF‐MFs have any effects on cognitive functions. Bioelectromagnetics 31:173–179, 2010. © 2009 Wiley‐Liss, Inc.     

Feature-short and feature-long discrimination learning in the pigeon: conditional control of a two-event temporal map

Eight pigeons were trained to peck an illuminated target key on discrete-trial fixed-interval schedules of reinforcement by food. Four birds were exposed to a feature-short (FS) task where a feature light signaled shortening of the forthcoming target-outcome interval from 30 to 15s, while the other four birds were exposed to a feature-long (FL) task where a feature light signaled extension of the forthcoming target-outcome interval from 15 to 30s. The discrimination performance measured by differential temporal distributions of pecks between featured and non-featured target trials suggested that the target-food temporal map was under conditional control of the feature light in both groups. The FS discrimination was more difficult to learn than the FL discrimination. This FS inferiority implies that our birds did not resort on the simple temporal discrimination by timing from the trial onset. The simple temporal discrimination account was also negated by the finding that increasing the feature-target gap did not have a predicted effect on the response distribution.     

猕猴前额叶皮层神经元在视觉延缓分辨活动中的放电活动

在已学会颜色延缓分辨的3只猕猴上,用钨丝微电极记录前额叶背外侧部皮层神经元的放电活动,着重分析神经元放电活动与颜色延缓分辨活动的各个时期之间的相互关系。延缓分辨任务开始时,同时把红色光和绿色光分别投射在测试板上的两个显示窗上,约持续1.2s(暗示期)。颜色光熄灭后2—4s(此为延缓期),各自位于每一显示窗下的两个反应键同时向猴方推出。自此,反应期开始,动物应马上有选择地作出按键反应。如果动物作出正确选择按红色光下的反应键,则给少量桔子汁作奖励。共记录了155个前额皮层单位。其中40个单位的放电频率在动物完成视觉延缓分辨作业过程中没有明显变化,另外115个单位与该任务的某些时期有关。大多数单位(n=99)在反应键推出时,或者在按反应键的前后有放电频率变化。这99个单位中,15个在暗示期和反应期内放电活动有变化(CR 型单位),13个在延缓期和反应期内放电活动有变化(DR 型单位),42个只在反应期内或反应期后放电频率出现变化(R 型单位),其余29个单位则在分辨任务的各个时期都显示出放电活动变化(CDR 型单位)。上述这些单位中,有少数单位在动物作出正确反应时的放电型式与动物作出错误反应时的放电型式有明显不同。此外,即使动物对任务测试不作出按键反应时,也观察到16个单位的放电活动在任