Differences in startle modulation during instructed threat and selective attention

This study investigated whether attentional processes contribute to fear-potentiated startle. Ten subjects participated in a threat of shock experiment and an attentional control condition. In the threat of shock experiment, visual cues indicated whether or not an aversive shock might occur. In the attentional control, the shocks were replaced by faint vibrotactile stimuli that had to be counted. The P300 amplitudes of the ERP evoked by the visual cues did not differ under threat and counting, which suggested that both conditions engaged attention to the same extent. In contrast, startle potentiation in the threat condition was an order of magnitude larger than the marginally significant attentional startle facilitation in the counting condition. These results indicate that an attentional contribution to fear-potentiated startle under the present experimental conditions is small. In addition, contextual effects of threat of shock became manifest as baseline startle was facilitated relative to the attention condition. This may reflect a more sustained state of anxiety on which cue-specific fear responses are superimposed.     

Fusion of vestibular and podokinesthetic information during self-turning towards instructed targets

When observers step about their vertical axis ("active turning") without vision they dispose of essentially two sources of information that can tell them by how much they have turned: the vestibular cue which reflects head rotation in space and the "podokinesthetic" cue, a compound of leg proprioceptive afferents and efference copy signals which reflects the observer's motion relative to his support. We ask how these two cues are fused in the process leading to the perception of self-displacement during active turning. To this end we compared the performance of observers in three angular navigation tasks which differed with regard to the number and type of available motion cues: (1) Passive rotation, vestibular cue ( ves) only; observers are standing on a platform which is being rotated. (2) Treadmill stepping, podokinesthetic cue ( pod) only; observers step counter to the rotating platform so as to remain stable in space. (3) Active turning, ves and pod available; observers step around on the stationary platform. In all three tasks, angular velocity varied from trial to trial (15, 30, 60 degrees /s) but was constant during trials. Perception was probed by having the observers signal when they thought to have reached a previously instructed angular displacement, either in space or relative to the platform ("target"; range 60-1080 degrees ). Performance was quantified in terms of the targeting gain (displacement reached by the observer divided by target angle) and of the random error ( E(r)), which records an observer's deviation during single trials from his average performance. Confirming previous observations, E(r) was found to be significantly smaller during active turning than during passive turning, and we now complement these observations by showing that it is also significantly smaller than during treadmill stepping. This behaviour of E(r) is compatible with the idea that ves and pod be averaged during active turning. On the other hand, the observed characteristics of the targeting gain ( G(T)) support this idea only for the case of fast rotations (60 degrees /s); at lower velocities, the gain found during active turning was clearly not the average of the G(T) values recorded in the passive and the treadmill modes. We therefore also discuss alternative scenarios as to how ves and pod could interact, among these one based on the concept of a vestibular eigenmodel. A common denominator of these scenarios is that ves assumes the role of a prerequisite for an optimal use of pod during turning on a stationary support, without itself entering the calculation of displacement perception; this perception would be based exclusively on pod. Finally, it was a consistent observation that during passive rotations cognitive mechanisms fill in for the decaying vestibular signal in the context of the present navigation task, enabling observers to achieve large displacements surprisingly well although the duration of these movements exceeds by far the conventionally cited value of the central vestibular time constant (=20 s).     

Oscillations of local field potentials in the rat dorsal striatum during spontaneous and instructed behaviors

Oscillatory activity is a candidate mechanism for providing frequency coding for the generation, storage and replay of sequential representations of events and episodes. We recorded local field potentials (LFPs) and spike activity in the striatum, a basal ganglia structure implicated in behavioral action-sequence learning and performance, as rats engaged in spontaneous and instructed behaviors in a T-maze task. We found that during voluntary behaviors, striatal LFPs exhibit prominent theta-band oscillations together with rhythms at higher and lower frequencies. Analysis of the theta-band activity demonstrated that these oscillations are strongly modulated during task performance and increase as the animals choose and execute their turning responses in the cue-instructed T-maze task. These theta rhythms are locally generated and are coherent across large parts of the striatum. We suggest that modulation of oscillatory activity in the striatum may be a key feature of neural processing related to the control of voluntary behavior.     

Differential effects of instructed and objective feedback reliability on feedback‐related brain activity

Feedback reliability refers to the probability that the same decision leads to the same positive or negative feedback in the future. Previous research has shown that unreliable feedback is associated with attenuated feedback‐related brain activity in ERPs, represented by a reduced fronto‐central valence effect (feedback‐related negativity or reward positivity) and a reduced feedback‐related P3. Here, we asked whether these effects reflect top‐down mechanisms or whether they can be explained by implicit feedback‐outcome contingency learning. In two experiments, participants performed a trial‐and‐error learning task while subjective or objective feedback reliability was varied across blocks. In Experiment 1, we manipulated instructed feedback reliability while holding objective feedback reliability constant. Low instructed feedback reliability led to an attenuation of the fronto‐central valence effect and the P3. In Experiment 2, we manipulated objective feedback reliability while holding instructed feedback reliability constant. Here, no modulation of feedback‐related brain activity was observed. These results suggest that effects of feedback reliability are driven by top‐down mechanisms based on explicit knowledge. Specifically, effects on the fronto‐central valence effect could indicate a devaluation of unreliable feedback or a bias on the generation or utilization of reward prediction errors.     

Only reappraisers profit from reappraisal instructions: Effects of instructed and habitual reappraisal on stress responses during interpersonal conflicts

Conflicts are an undesirable yet common aspect of daily interactions with wide‐ranging negative consequences. The present research aimed to examine the buffering effect of experimentally instructed reappraisal on self‐reported, physiological and behavioral stress indices during interpersonal conflicts, taking into account habitual emotion regulation strategies. For this, 145 participants experienced a standardized laboratory conflict with the instruction to either reappraise (n = 48), to suppress (n = 50), or with no instruction (n = 47) while cardiovascular and neuroendocrine measures were taken. Participants were allowed to eat sweet and salty snacks during the conflict situation. Prior to as well as after the conflict, participants reported on their subjective stress level. Reappraisal instructions were only effective for high habitual reappraisers who exhibited lower cardiovascular and cortisol reactivity and demonstrated fewer snack‐eating behaviors under reappraisal instructions than under suppression or no instructions. The opposite pattern emerged for low habitual reappraisers. Neither experimentally instructed nor habitual reappraisal by itself reduced the negative effects of conflicts. Our findings complement the literature on the diverging effects of instructed reappraisal in tense social interactions.     

Dectin-1与非Toll样模式识别受体免疫识别的研究进展

Toll样受体（TLR）是一类天然免疫相关的模式识别受体（PRR），在机体抵御感染中发挥着极为重要的作用。除TLR外，目前还发现了很多其它种类PRR，这些非Toll样PRR在天然免疫中的作用也是不可缺少的，它们既可以与TLR协同作用，也可以单独发挥作用。Dectin-1是近年来颇受关注的一种非Toll样PRR，属于NK细胞受体样C型凝集素，是一种Ⅱ型跨膜受体，通过对真菌的识别参与免疫效应细胞的吞噬及杀伤过程，诱导机体产生一系列的细胞因子及趋化因子，从而参与机体防御真菌病原体的天然免疫反应，但在某些情况下也可能引起自身免疫性疾病的发生。     

海马区神经元和神经元群放电模型的研究现状

随着对大脑认知功能研究的发展,在微观—介观水平上对海马区神经元及神经元群放电及其功能的研究已成为近年来脑认知功能研究的热点。从信息学的角度,对神经元和神经元群放电进行建模与仿真是该领域研究的重要方向之一。介绍海马区单个神经元放电模型和神经元群的几类放电模型及其应用概况,并探讨各类模型的特点和面临的问题。     

Effects of visual stimulation on LFPs, spikes, and LFP-spike relations in PRR

Local field potentials (LFPs) have shown diverse relations to the spikes across different brain areas and stimulus features, suggesting that LFP-spike relationships are highly specific to the underlying connectivity of a local network. If so, the LFP-spike relationship may vary even within one brain area under the same task condition if neurons have heterogeneous connectivity with the active input sources during the task. Here, we tested this hypothesis in the parietal reach region (PRR), which includes two distinct classes of motor goal planning neurons with different connectivity to the visual input, i.e., visuomotor neurons receive stronger visual input than motor neurons. We predicted that the visual stimulation would render both the spike response and the LFP-spike relationship different between the two neuronal subpopulations. Thus we examined how visual stimulations affect spikes, LFPs, and LFP-spike relationships in PRR by comparing their planning (delay) period activity between two conditions: with or without a visual stimulus at the reach target. Neurons were classified as visuomotor if the visual stimulation increased their firing rate, or as motor otherwise. We found that the visual stimulation increased LFP power in gamma bands >40 Hz for both classes. Moreover, confirming our prediction, the correlation between the LFP gamma power and the firing rate became higher for the visuomotor than motor neurons in the presence of visual stimulation. We conclude that LFPs vary with the stimulation condition and that the LFP-spike relationship depends on a given neuron's connectivity to the dominant input sources in a particular stimulation condition.     

Spiking and nonspiking classes of oligodendrocyte precursor glia in CNS white matter

A defining feature of glial cells has been their inability to generate action potentials. We show here that there are two distinct types of morphologically identical oligodendrocyte precursor glial cells (OPCs) in situ in rat CNS white matter. One type expresses voltage-gated sodium and potassium channels, generates action potentials when depolarized and senses its environment by receiving excitatory and inhibitory synaptic input from axons. The other type lacks action potentials and synaptic input. We found that when OPCs suffered glutamate-mediated damage, as occurs in cerebral palsy, stroke and spinal cord injury, the action potential-generating OPCs were preferentially damaged, as they expressed more glutamate receptors, and received increased spontaneous glutamatergic synaptic input in ischemia. These data challenge the idea that only neurons generate action potentials in the CNS and imply that the development of therapies for demyelinating disorders will require defining which OPC type can carry out remyelination.     

Effects of instructed focus and task difficulty on concurrent walking and cognitive task performance in healthy young adults

Dual task paradigms can be used to examine the interactions between cognition and the control of posture and gait. Measuring and interpreting changes in dual task performance is challenging, however, because many factors can influence performance. This study examined the effects of instructed focus and walking task difficulty, and the interaction between these factors, on dual task performance in healthy young adults. Fifteen participants performed a cognitive task while walking with either a usual base or a narrow base of support. Participants were instructed to focus on either the cognitive task or walking. Trade-offs both within and between tasks were assessed using the modified attention allocation index and the performance operating characteristic. Instructed focus influenced both the cognitive task and walking. Performance on the cognitive task was faster with instructions to focus on the cognitive task, and walking was faster (and more accurate in the narrow-base condition) with instructions to focus on walking. Walking task difficulty did not affect cognitive performance but did affect walking, with faster walking in the usual-base versus narrow-base condition. There was evidence of an interaction, with greater effects of instructed focus on the cognitive task during usual versus narrow-base walking. These results support the idea that the ability to flexibly shift attention allocation and task performance in response to instructions depends on the difficulty of the postural control task. The modified attention allocation index and the performance operating characteristic were instrumental in fully characterizing trade-offs between and within tasks in order to understand dual task performance changes. A clearer understanding of the factors that affect dual task walking and the interactions between these factors has important implications for the assessment of dual task performance in both clinical and research settings.     

Complement activation reaches maximum during equilibrium between antigen and antibody in an in vitro model for thrombolysis with streptokinase

Treatment with streptokinase (SK) of patients with acute myocardial infarction (AMI) is known to activate the complement system. In a previous investigation we found a great variation in the degree of complement activation taking place during infusion of SK in patients with AMI (range: 0-293% increase in pretreatment complement split product 3d (C3d) levels). In this in vitro study we added SK to serum with different concentrations of SK-antibodies (SK-Ab) and found that both the relative concentrations and the total concentrations of SK and Ab determined the degree of complement activation elicited by SK. This finding was in accordance with the Kendall-Heidelberger equation of antigen-antibody equivalence. Furthermore, we found parallel rises in C3d and C4d, indicating that complement was activated via the classical pathway. A condition for maximal complement activation is antigen-antibody equivalence.     

Sympathetic and cardiovascular activity during cataplexy in narcolepsy

Autonomic nervous system activity changes have been described during cataplexy as playing a role in triggering it. To confirm these previous findings, we investigated the time course of sympathetic and cardiovascular activities during cataplexy. We made for the first time microneurographic recordings of 10 cataplectic episodes in three patients with hypocretin‐deficient narcolepsy. During microneurography, muscle sympathetic nerve activity (MSNA) was recorded simultaneously with heart rate (HR), respiratory movements, arterial finger blood pressure (BP), electroencephalography, electro‐oculogram and superficial electromyogram. Results showed no significant autonomic changes before the onset of the cataplectic episodes. Cataplexy was associated with a significant increase in MSNA and BP compared with baseline, whereas HR was markedly decreased. An irregular breathing pattern mainly characterized by apnea typically occurred during the attacks. In conclusion, our findings did not show significant changes in autonomic activity prior to cataplexy onset, ruling out a triggering role of the autonomic system. However, cataplexy was associated with co‐activation of sympathetic and parasympathetic autonomic systems, a pattern reminiscent of that reported during the vigilance reaction in animals.     

Stereotypical spatiotemporal activity patterns during slow-wave activity in the neocortex

Alternating epochs of activity and silence are a characteristic feature of neocortical networks during certain sleep cycles and deep states of anesthesia. The mechanism and functional role of these slow oscillations (<1 Hz) have not yet been fully characterized. Experimental and theoretical studies show that slow-wave oscillations can be generated autonomously by neocortical tissue but become more regular through a thalamo-cortical feedback loop. Evidence for a functional role of slow-wave activity comes from EEG recordings in humans during sleep, which show that activity travels as stereotypical waves over the entire brain, thought to play a role in memory consolidation. We used an animal model to investigate activity wave propagation on a smaller scale, namely within the rat somatosensory cortex. Signals from multiple extracellular microelectrodes in combination with one intracellular recording in the anesthetized animal in vivo were utilized to monitor the spreading of activity. We found that activity propagation in most animals showed a clear preferred direction, suggesting that it often originated from a similar location in the cortex. In addition, the breakdown of active states followed a similar pattern with slightly weaker direction preference but a clear correlation to the direction of activity spreading, supporting the notion of a wave-like phenomenon similar to that observed after strong sensory stimulation in sensory areas. Taken together, our findings support the idea that activity waves during slow-wave sleep do not occur spontaneously at random locations within the network, as was suggested previously, but follow preferred synaptic pathways on a small spatial scale.     

Thyroid function and motor activity in dogs during development

The intensity of motor activity and the serum level of protein-bound iodine (PBI) were investigated in 62 puppies aged from 1 to 12 months. During the first 4 months of life a parallel increase in motor activity and PBI of the puppies was observed. The increase in motor activity of puppies between the ages of 7 and 9 months was not accompanied by any increase in PBI. In hypothyroidism caused by methimazole in puppies aged 1 and 3 months increased motor activity was observed, whereas in animals aged 7 months it was reduced. A higher intensity of motor activity than in the control animals also was observed 1 month after the operation in puppies thyroidectomized at the ages of 1 and 3.5 months. The activity of puppies thyroidectomized at the age of 1 month was sharply reduced 2–4 months after the operation. In dogs thyroidectomized at the ages of 7.5 and 11.5 months, reduced activity was observed as early as 1 month after the operation. The data showing opposite effects of thyroid hormones on the behavior of puppies at different ages point to a complex relationship between motor activity and thyroid function.Laboratory of Comparative Ontogeny of Higher Nervous Activity, I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR V. N. Chernigovskii.) Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 87, No. 2, pp. 108–110, February, 1979.     

Ventilation and acid-base balance during graded activity in lizards

Arterial PCO2, hydrogen ion ([H+]a), and lactate ([L]a) concentrations, rates of metabolic CO2 production (VCO2) and O2 consumption (VO2), and effective alveolar ventilation (Veff) were determined in the lizards Varanus exanthematicus and Iguana iguana at rest and during steady-state treadmill exercise at 35 degrees C. In Varanus, VCO2 increased ninefold and VO2 sixfold without detectable rise in [L]a at running speeds below 1.0 to 1.5 km x h-1. In this range, Veff increased 12-fold resulting in decreased levels of PaCO2 and [H+]a. At higher speeds [L]a rose. Increments of 5 mM [L]a were accompanied by hyperventilation, reducing PaCO2 and thus maintaining [H+]a near its resting level. When [L]a increased further, [H+]a increased. Sustainable running speeds (0.3-0.5 km x h-1 and below) were often associated with increased VO2, VCO2, and [L]a in Iguana. Sixfold increases in VCO2 and 9-mM increments in [L]a were accompanied by sufficient increase in Veff (9-fold) to maintain [H+]a at or below its control level. When [L]a increased further, [H+]a increased. These results indicate that both lizard species maintain blood acid-base homeostasis rather effectively via ventilatory adjustments at moderate exercise intensities.     

Apoptosis and proliferative activity in endometrium during peritoneal endometriosis

Apoptosis and proliferative activity of the glandular epithelium and endometrial stroma in patients with peritoneal endometriosis and in women of reproductive age without endometriosis were studied at various stages of menstrual cycle. Differences in the intensity of apoptosis were revealed manifesting in changed expression of proteins in the glandular epithelium of patients with endometriosis during the secretory phase of the menstrual cycle compared to normal. Proliferative activity of the glandular epithelium in the proliferative phase was higher than in the secretory phase. Our results suggest that the imbalance between apoptosis proteins in the endometrium plays a role in the pathogenesis of peritoneal endometriosis. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 141, No. 2, pp. 165–168, February, 2006     

Non-receptor tyrosine kinase 2 reaches its lowest expression levels in human breast cancer during regional nodal metastasis

Almost half of breast Ductal Carcinoma in situ are likely to remain non threatening in situ lesions with no invasion to the surrounding stroma and no metastases. The majority of focal disruptions in myoepithelial (ME) cell layers indicative of invasion onset were found to be overlying epithelial cell clusters with no or substantially reduced estrogen receptor α (ERα) expression. Here we report the down-regulation of tyrosine kinase-2 (TYK2) and up-regulation of strumpellin expression, among other proteins in ERα(−) cells located at disrupted ME layers compared to adjacent ERα(+) cells overlying an intact myoepithelial layer. ERα(+) and ERα(−) cells were microdissected from the same in vivo human breast cancer tissues, proteins were extracted and separated utilizing Differential in-Gel Electrophoresis followed by trypsin digestion, MALDI-TOF analysis, and protein identification. Proteins expressed by ERα(−) cell clusters were found to express higher levels of strumpellin that binds to valosin-containing protein (VCP) to slow-down wound closure and promote growth; and lower levels of TYK2, a jak protein necessary for lineage specific differentiation. TYK2 levels were further analyzed by immunohistochemistry in a cohort composed of 70 patients with broad clinical characteristics. TYK2 levels were minimal in TxN1M0 breast cancers which is the stage where the initial regional lymph node metastasis is observed. Our data highlight the role of TYK2 downregulation in breast cancer cell de-differentitation and initiation of regional metastasis. In addition, the aggressiveness of the ERα(−) cell clusters compared to ERα(+) ones present in the same duct of the same patient was confirmed.