Electrical microstimulation of primate posterior parietal cortex initiates orienting and alerting components of covert attention

The posterior parietal cortex (PPC) is implicated in the control of visuospatial orienting, including both overt saccadic eye movements and covert shifts of attention (i.e., attention to a location other than at visual fixation). Some studies have suggested that the attentional system is part of the premotor processing in the brain, while others suggest they are separate. Here, we test how the PPC controls covert attention shifts in the absence of executed eye movements. Electrical microstimulation was applied to the right PPC while monkeys performed a spatial, cued target detection task, in which they were not allowed to move their gaze. At high currents, contralateral saccades were evoked. With currents below the thresholds for eliciting saccades, microstimulation produced a purely attentional shift (as indexed by decreased target reaction time) when a cue and target were presented in the contralateral visual field. This suggests that microstimulation can move attention specifically in the absence of any overt movements of the eyes or limbs. In addition, there was a reduction in reaction times in trials that did not evoke attentional orienting, suggesting a more general alerting effect of microstimulation These data provide direct evidence that the PPC may be a source of both attentional modulation of neuronal responses and saccadic eye movements to peripheral visual stimuli.     

Effects of posterior parietal lesions on visually guided movements in monkeys

Summary Four monkeys were trained to position, with either hand, a vertical rod in front of one of 5 target lights spaced 20° apart on a semicircular screen. After the monkeys had reached the preoperative criterion (80% trials correct per session) they received a 1- or 2-stage bilateral lesion of posterior parietal cortex restricted to area 7. The lesion produced in all the monkeys considerable but temporary changes in movement latency, accuracy, velocity and duration. Latency increase appeared to be independent of changes in the other parameters. After the first lesion, movement latency increased for the contralateral arm in both left and right working spaces, from 100 ms up to 400 ms depending on the animal. A second lesion symmetrical to the first one increased movement latency of the arm contralateral or ipsilateral to the last lesion, depending on the time interval between the two lesions. In addition, unilateral lesions of area 7 induced a gross inaccuracy in movements of the arm contralateral to the lesion, more marked in the contralateral working space. These lesions also increased movement peak velocity and simultaneously decreased movement duration for the arm contralateral to the lesion. The increase in velocity appeared to be related to the decrease in duration. A second lesion of area 7 in the opposite hemisphere similarly affected accuracy, velocity and duration but for the arm contralateral to the second lesion.     

Effects of repetitive transcranial magnetic stimulation over dorsolateral prefrontal and posterior parietal cortex on memory-guided saccades

We investigated the role of the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC) in a visuospatial delayed-response task in humans. Repetitive transcranial magnetic stimulation (20 Hz, 0.5 s) was used to interfere temporarily with cortical activity in the DLPFC and PPC during the delay period. Omnidirectional memory-guided saccades with a 3-s delay were used as a quantifiable motor response to a visuospatial cue. The question addressed was whether repetitive transcranial magnetic stimulation (rTMS) over the DLPFC or PPC during the sensory of memory phase affects accuracy of memory-guided saccades. Stimulation over the primary motor cortex served as control. Stimulation over the DLPFC significantly impaired accuracy of memory-guided saccades in amplitude and direction. Stimulation over the PPC impaired accuracy of memory-guided saccades only when applied within the sensory phase (50 ms after cue offset), but not during the memory phase (500 ms after cue offset). These results provide further evidence for a parieto-frontal network controlling performance of visuospatial delayed-response tasks in humans. It can be concluded that within this network the DLPFC is mainly concerned with the mnemonic respresentation and the PPC with the sensory representation of spatially defined perceptual information. Received: 22 April 1996/Accepted: 16 June 1997     

The anterior cingulate cortex is involved in retrieval of long-term/long-lasting but not short-term memory for step-through inhibitory avoidance in rats

It is known that the anterior cingulate cortex (ACC) is involved in the formation of contextual fear memory. It has been shown that the ACC is important for the retrieval of long-term contextual fear memory. In order to further examine the role of the ACC in fear memory, we investigated the effects of chemical lesion to or reversible inactivation of the ACC on the retrieval of long-term and short-term step-through inhibitory avoidance (IA) memory. Chemical lesion to the ACC by quinolinic acid severely impaired the retrieval of 15-day and 29-day memories for one-trial step-through IA. Pre-retrieval inactivation of the ACC by locally infusing muscimol, a selective GABA_A receptor agonist, produced a severe deficit in 7-day, 4-day and 1-day IA memories, with no effect on 2-h and 6-h memories. Thus, the ACC is required for the retrieval of long-term/long-lasting IA memory, but is dispensable for short-term one.     

Memory related motor planning activity in posterior parietal cortex of macaque

Summary Unit recording studies in the lateral bank of the intraparietal cortex (area LIP) have demonstrated a response property not previously reported in posterior cortex. Studies were performed in the Rhesus monkey during tasks which required saccadic eye movements to remembered target locations in the dark. Neurons were found which remained active during the time period for which the monkey had to withhold eye movements while remembering desired target locations. The activity of the cells was tuned for eye movements of specific direction and amplitude, and it was not necessary for a visual stimulus to fall within the response field. The responses appeared to represent a memory-related motor-planning signal encoding motor error. The relation of the activity to the behavior of the animal suggests that the response represents the intent to make eye movements of specific direction and amplitude.     

Influences of lesions of parietal cortex on visual spatial attention in humans

Summary Several brain areas have been identified with attention, because damage to these regions leads to neglect and extinction. We have tested elements of visual attentional processing in patients with parietal, frontal, or temporal lesions and compared their responses to control subjects. Normal humans respond faster in a reaction time task when the spatial location of a target is correctly predicted by an antecedent stimulus (valid cue) than when the location is incorrectly predicted (invalid cue). The cue is hypothesized to shift attention towards its location and thereby facilitate or impede response latencies. The reaction times of individuals with damage to the parietal lobe are somewhat slowed for targets ipsilateral or contralateral to the side of the lesion if the targets are preceded by valid cues. These same patients are extremely slow in responding to targets in the visual field contralateral to the lesion when the cue has just appeared in the unaffected (ipsilateral) visual field. In addition, these individuals are especially slow in responding to targets in either visual field when the lights are preceded by weak, diffuse illumination of the entire visual field. Patients with lesions of the frontal lobe have very slow reaction times in general and, as is the case for patients with lesions of the temporal lobe, are slow in all conditions for targets in the field contralateral to the lesion. These patterns are probably not associated with attentional defects. For patients with parietal lesions, these studies demonstrate a further deficit in a cued reaction-time task suggesting abnormal visual attention. Since different sites of brain damage yield different patterns of responses, tests such as these could be of analytic and diagnostic value.     

Functional properties of rotation-sensitive neurons in the posterior parietal association cortex of the monkey

We studied the functional properties of rotation-sensitive (RS) neurons of the posterior parietal association cortex in detail. We classified 58 neurons as RS neurons on the basis of statistical analysis, to indicate that their responses to rotary movement were significantly greater (P<0.01) than those to linear movement of the same stimulus. We calculated rotation index, 1 — (L/R), in 82 cells, where L/R is the ratio of net response to linear movement to that to rotary movement. All the RS neurons had rotation index greater than or equal to 0.3. The recording site of these RS neurons was localized in the posterolateral part of area PG (area 7a of Vogt), on the anterior bank of the caudal superior temporal sulcus (STS), in the region partly overlapping the medial superior temporal (MST) area. We compared the response of RS neurons to rotation with that to shearing movement as well as to linear movement. In the majority of RS neurons the ratio of shearing response to rotation response (S/R) was smaller than the ratio of linear response to rotation response (L/R), indicating that the response to rotation was not due to a simple combination of linear movements in the opposite direction. Most of the RS neurons responded to the rotary movement of a single spot as well as that of a slit, although the response was smaller (average 70%) for the former. Most of the RS neurons had large receptive fields (60–180° in diameter) and their responses were independent of the position within the receptive field. The responses of most RS neurons increased monotonically with the increase in angular velocity and were also dependent on the size of the stimulus, although the rate of increase was small when the length was more than 10°. The majority of RS neurons (37/58) responded better to rotation in depth than to that in the frontoparallel plane. Some of them (12/37) responded to diagonal rotation rather than to sagittal or horizontal rotation. We found that some depth RS neurons showed reversal in the preferred direction when we used a trapezoidal window-like plate as the rotating stimulus in the monocular viewing condition, just as occurs in the case of the Ames window illusion. The response of some RS neurons (5/7) was enhanced by tracking eye movement. The enhanced responses were observed during rotary tracking but not during linear tracking. Other RS neurons (n = 2) showed maximum response to the rotation of the monkey chair in the light, as a result of convergence of visual and vestibular signals. We concluded that the continuous change of direction of movement was the most important cue for RS neurons to respond selectively to rotary movement in contrast to linear translational movement, and that these neurons were likely to discriminate the direction and orientation of the plane of rotation of the object in space.     

Facilitation of neuronal activity in somatosensory and posterior parietal cortex during prehension

In order to study prehension in a reproducible manner, we trained monkeys to perform a task in which rectangular, spherical, and cylindrical objects were grasped, lifted, held, and lowered in response to visual cues. The animal’s hand movements were monitored using digital video, together with simultaneously recorded spike trains of neurons in primary somatosensory cortex (S-I) and posterior parietal cortex (PPC). Statistically significant task-related modulation of activity occurred in 78% of neurons tested in the hand area; twice as many cells were facilitated during object acquisition as were depressed. Cortical neurons receiving inputs from tactile receptors in glabrous skin of the fingers and palm, hairy skin of the hand dorsum, or deep receptors in muscles and joints of the hand modulated their firing rates during prehension in consistent and reproducible patterns. Spike trains of individual neurons differed in duration and amplitude of firing, the particular hand behavior(s) monitored, and their sensitivity to the shape of the grasped object. Neurons were classified by statistical analysis into groups whose spike trains were tuned to single task stages, spanned two successive stages, or were multiaction. The classes were not uniformly distributed in specific cytoarchitectonic fields, nor among particular somatosensory modalities. Sequential deformation of parts of the hand as the task progressed was reflected in successive responses of different members of this population. The earliest activity occurred in PPC, where 28% of neurons increased firing prior to hand contact with objects; such neurons may participate in anticipatory motor control programs. Activity shifted rostrally to S-I as the hand contacted the object and manipulated it. The shape of the grasped object had the strongest influence on PPC cells. The results suggest that parietal neurons monitor hand actions during prehension, as well as the physical properties of the grasped object, by shifting activity between populations responsive to hand shaping, grasping, and manipulatory behaviors. Received: 1 October 1998 / Accepted: 4 May 1999     

Long-term object location memory in rats: Effects of sample phase and delay length in spontaneous place recognition test

This study investigates the effects of sample phase and delay length on discrimination performance in the spontaneous place recognition (SPR) test in rats. Rats were allowed to explore an arena where two identical objects were presented for 5–20 min (sample phase). After a delay interval, rats were placed again in the same arena but one of the two objects was moved to a novel place (test phase). Results showed that when the sample phase was as long as 20 min, rats preferentially explored the moved object during the test phase even after a 6–24 h delay was interposed. Further sequential and cumulative analyses of the test phase revealed that the preference for the object in a novel place was evident in the first and 2nd min of the test phase in rats with a longer sample phase duration. Correlation analysis showed that locomotor activity and object exploration in the sample phase were not decisive factors in spatial memory performance. The present results demonstrate the importance of the sample phase exposure time and the test phase length.     

Neuronal correlates of signal detection in the posterior parietal cortex of rats performing a sustained attention task

The posterior parietal cortex (PPC) plays an integral role in visuospatial attention. Evidence suggests that neuronal activity in the PPC predicts the allocation of attention to stimuli. The present experiment tested the hypothesis that in rats performing a sustained attention task, the detection of signals, as opposed to missed signals, is associated with increased PPC unit activity. Single unit activity was recorded from the PPC of rats and analyzed individually and as a population vector for each recording session. A population of single units (28/111) showed significant activation evoked by signals on trials resulting in correct performance (hits). A smaller population of neurons (three/111) was activated on trials in which signals were not detected by the animals (misses). Analysis of populations of simultaneously recorded neurons indicated increased activation predicting signal detection; no population of neurons was activated on trials in which the animal incorrectly pressed the hit lever following nonsignals. The increased, hit-predicting activity was not modulated by signal duration or the presence of a visual distractor, although the distractor reduced the number of trials in which hit-predicting activity and subsequent correct detection occurred. These findings indicate that attentional signal processing in the PPC integrates successful detection of signals.     

PTSD大鼠海马CA1区和前额叶皮层突触小泡蛋白的表达

目的:观察创伤后应激障碍(posttraumatic stress disorder,PTSD)大鼠海马CA1区和前额叶皮层(prefrontal cortex,PFC)突触小泡蛋白(synaptophysin)的表达,探讨PTSD大鼠空间记忆损伤的机制。方法:健康成年SD大鼠36只,随机分为正常对照组和模型组,每组18只。模型组采用单次延长应激(single prolonged stress,SPS)构建PTSD大鼠模型。Morris水迷宫实验检测2组大鼠的学习记忆能力,利用免疫组化、Western blot和免疫荧光实验检测海马CA1区和PFC突触小泡蛋白的表达情况。结果:经过Morris水迷宫实验,模型组大鼠从第2天开始逃避平台的潜伏期较对照组均显著延长(P 0.01),目标象限的停留时间均明显降低(P 0.01),穿越原平台位置的次数也明显减少(P 0.01)。在免疫组化、Western blot和免疫荧光实验中,模型组大鼠海马CA1区和PFC突触小泡蛋白的表达较对照组均明显减少(P 0.05或P 0.01)。结论:创伤后应激障碍大鼠空间记忆能力减退,可能与海马CA1区和PFC突触小泡蛋白的表达减少有关。     

Effects of additional cues on passive avoidance learning and extinction in rats with hippocampal lesions

Following the acquisition of a water-rewarded approach response in a straight runway, the effects of introducing shock in the goal box (passive avoidance - PA) or withdrawing reinforcement (extinction) were compared in hippocampal, cortical, and operated control groups of rats. Under standard test conditions, hippocampal groups were impaired in PA learning and showed strong resistance to extinction, relative to the control groups. When additional cues were provided such that external stimuli associated with goal box events could be easily detected early in the runway, performance differences between the hippocampal and control groups were eliminated in the PA test and significantly reduced in extinction. The results emphasize the inefficient processing by hippocampally-damaged animals of stimulus cues following a shift in experimental contingencies.     

丙泊酚对大鼠空间关联记忆能力影响的水迷宫行为测试研究

目的研究注射临床低剂量和高剂量的丙泊酚对大鼠空间关联记忆能力的影响。方法将30只大鼠随机分成3组：对照组、临床低剂量0．1mg／（kg·min）组和临床高剂量0．5mg／（kg·min）组。在注射丙泊酚1d后进行水迷宫实验,包括4d的定位航行和1d的空间探索实验。在定位航行实验中分别对3组大鼠进行I、Ⅱ和Ⅲ象限入水的训练,并记录3组大鼠的逃避潜伏期、游泳路程和游泳速度。在空间探索实验中将大鼠从未训练的Ⅳ象限入水,分别记录平台象限游泳时间、第一环点数以及总得分。结果在第1,2天的定位航行实验中,低剂量组与对照组大鼠的逃避潜伏期没有统计学差异（p〉0．05）;高剂量组逃避潜伏期比对照组显著延长（P〈O．05）。第3,4天的定位航行实验中,3组大鼠之间均未见差异（p〉0．05）。在空间探索实验中,从未训练的Ⅳ象限入水时,对照组、低剂量组和高剂量组大鼠的总得分分别为（2509．36±190．72）、（2378．55±210．69）和（1954．85±174．20）。低剂量组和对照组没有显著性差异（P〉0．05）;高剂量组与对照组存在显著性差异（P〈O．05）,即高剂量组比对照组总得分低。结论注射低剂量的丙泊酚不影响大鼠的空间关联记忆和空间记忆能力;高剂量丙泊酚在注射后前2d内降低大鼠的空间记忆能力,但2d后对大鼠的空间记忆能力没有影响,说明高剂量的丙泊酚降低了大鼠的空间关联记忆能力。     

慢性不可预见性应激对大鼠大脑皮质及海马酪氨酸硝基化的影响

目的：探讨慢性应激能否使SD大鼠大脑皮质神经细胞产生蛋白质酪氨酸硝基化。方法：将40只SD大鼠随机分为对照组和慢性不可预见性应激组各20只,用慢性不可预见性应激模型法造模,时间分为1周、2周和3周,每周用Open-field法给予行为学评分,并用组织化学和免疫组织化学法染色观察大脑神经细胞形态和其蛋白质酪氨酸硝基化的变化。结果：慢性不可预见性应激组与对照组神经细胞形态有明显的不同,且出现蛋白质酪氨酸硝基化,两组相比具有显著统计学意义。结论：慢性不可预见性应激模型鼠的大脑皮质神经细胞发生慢性应激损伤,是有效的慢性应激模型,其发生机制至少部分与NO~ 的产生而导致神经细胞蛋白质酪氨酸硝基化有关。     

Comparison of effects of pentobarbital and ethanol on the neuronal activity in the posterior parietal association cortex

The problem of this study was whether the effects produced by alcohol in the posterior parietal association cortex are specific to this drug or shared by other centrally acting depressant drugs such as barbiturates. The effect of graded doses of pentobarbital on multineuronal impulse activity was recorded with transdural microelectrode technique in 30 expts. in Brodmann's area 7 of five stump-tailed monkeys (Macaca speciosa). The results were compared with those from 32 expts. performed with alcohol and published separately. The dosage of the two drugs was determined on the basis of the monkeys' sensori-motor coordination which was assessed with a rating scale of reaching accuracy for food rewards. There were several recording sites where the actions of the two drugs were similar at similar behavioural levels of intoxication. However, in the distribution of effects among various functional types of recording sites a significant difference was found between pentobarbital and alcohol. Alcohol commonly diminished cellular activity related to motor behaviour (reaching, grasping) and only rarely responses to somesthetic stimuli, whereas the effects of pentobarbital were the opposite being most common on somatosensory responses and least common on activity related to motor behaviour. Also responses to visual stimuli were more sensitive to pentobarbital than to alcohol. The actions of pentobarbital and alcohol on responses evoked by sensory stimulation differed significantly (P < 0.01). We conclude that significant differences exist in the mechanisms of action of alcohol and barbiturate on the associative systems of the brain.     

CGRP对局灶性脑缺血再灌注大鼠顶叶皮质CREB和p-CREB的上调作用

目的：探讨外源性降钙素基因相关肽（CGRP）对局灶性脑缺血再灌注大鼠顶叶皮质CREB和磷酸化CREB（p-CREB）表达的影响。方法:用线栓法阻塞大鼠右大脑中动脉制作局灶性脑缺血再灌注模型，应用免疫组织化学、Western blotting和图像分析方法检测大鼠手术侧顶叶皮质CREB和p-CREB表达。结果:缺血再灌注组大鼠顶叶皮质CREB表达少于假手术组，CGRP组大鼠顶叶皮质CREB表达多于缺血再灌注组（P<0.05）。假手术组右侧顶叶皮质p-CREB表达很少，缺血再灌注组顶叶皮质p-CREB表达多于假手术组，CGRP组p-CREB表达多于缺血再灌注组（P<0.05）。结论:CGRP上调局灶性脑缺血再灌注大鼠右侧顶叶皮质CREB和p-CREB的表达，CGRP对缺血神经元的保护作用可能是通过上调神经元内CREB和p-CREB来实现的。     

Opposite impact on <Superscript>14</Superscript>C-2-deoxyglucose brain metabolism following patterns of high and low frequency repetitive transcranial magnetic stimulation in the posterior parietal cortex

Repetitive transcranial magnetic stimulation (rTMS) appears capable of modulating human cortical excitability beyond the duration of the stimulation train. However, the basis and extent of this “off-line” modulation remains unknown. In a group of anesthetized cats, we applied patterns of real or sham focal rTMS to the visuo-parietal cortex (VP) at high (HF) or low (LF) frequency and recorded brain glucose uptake during (on-line), immediately after (off-line), or 1 h after (late) stimulation. During the on-line period LF and HF rTMS induced a significant relative reduction of ¹⁴C-2DG uptake in the stimulated VP cortex and tightly linked cortical and subcortical structures (e.g. the superficial superior colliculus, the pulvinar, and the LPl nucleus) with respect to homologue areas in the unstimulated hemisphere. During the off-line period HF rTMS induced a significant relative increase in ¹⁴C-2DG uptake in the targeted VP cortex, whereas LF rTMS generated the opposite effect, with only mild network impact. Moderate distributed effects were only recorded after LF rTMS in the posterior thalamic structures. No long lasting cortical or subcortical effects were detected during the late period. Our findings demonstrate opposite modulation of rTMS on local and distant effects along a specific network, depending on the pattern of stimulation. Such effects are demonstrated in the anesthetized animal, ruling out behavioral and non-specific reasons for the differential impact of the stimulation. The findings are consistent with previous differential electrophysiological and behavioral effects of low and high frequency rTMS patterns and provide support to uses of rTMS in neuromodulation. ^†Prof. Payne passed away in May 2004. This article is submitted in his memory.     

应用水迷宫测试糖尿病大鼠空间记忆能力变化的研究

目的 研究大鼠患糖尿病后,空间记忆能力和空间关联记忆能力受到的影响.方法 将70只SD大鼠（体质量180 g±20 g）随机分成3组,对照组、1型糖尿病组和2型糖尿病组.采用STZ一次性腹腔注射和联合高脂饲料喂养的方法分别制备1型和2型糖尿病大鼠模型,检测血糖水平.在造模成功的1个月和3个月后,分别进行水迷宫实验,包括4 d的定位航行和1 d的空间探索实验.结果 在糖尿病造模成功的1个月后,大鼠没有发生明显的空间记忆能力或空间关联记忆能力障碍.造模3个月后,在定位航行实验中,2组糖尿病大鼠的逃避潜伏期都比对照组时间长,具有统计学差异（P＜0.05）.实验第2天开始,对照组逃避潜伏期的下降趋势明显,而糖尿病组下降缓慢.1型和2型糖尿病组之间的逃避潜伏期没有显著差异（P＞0.05）.造模3个月后,在空间探索实验中,从训练过的Ⅰ象限入水时,2个糖尿病模型组平台象限游泳时间短,第1环点数和总得分等参数低,与对照组的差异都具有显著意义（P＜0.05）,2型糖尿病组的参数值比1型糖尿病组稍低.从未训练的Ⅳ象限入水时,糖尿病模型组的参数值也均低于正常对照组,具有统计学差异（P＜0.05）,且1型糖尿病组的总得分比2型糖尿病组更低一些.结论 1型或2型的糖尿病大鼠会发生空间记忆能力和空间关联记忆能力的下降.本实验中2型糖尿病组的空间记忆能力比1型糖尿病组受到了更明显的影响,而1型糖尿病组的空间关联记忆能力受到的影响比2型糖尿病组更大.     

NMDA receptors are involved in Ginkgo extract-induced facilitation on memory retention of passive avoidance learning in rats

Herbal therapies are commonly used to enhance memory and learning. Ginkgo biloba has shown to be one of the most popular herbs that is used to treat amnesia and retard age related memory deficits. Although, there have been several reports on the memory enhancing effects of Ginkgo, involvement of glutamatergic system that plays pivotal role in learning and memory has not been precisely assessed so far. The current study intended to investigate the effect of Ginkgo intake on amnesia while NMDA (N-methyl D-aspartic acid) receptors blocked by the administration of MK-801. The study used passive avoidance (PA) task to investigate the effect of chronic administration of Ginkgo extract (40 and 90 mg/kg; oral) on the memory span in male Wistar rats, suffering from MK-801-induced forgetfulness (0.06 and 0.1 mg/kg; i.p.). The results indicate that Ginkgo was able to remove MK-801-induced forgetfulness, indicating that Ginkgo can affect memory retention but not effect on passive avoidance acquisition, using pathways other than glutamatergic system as well. The results might indicate that Ginkgo extract can be effective in removing forgetfulness caused by inhibiting NMDA receptors from performing their activities.     

Effects of antibodies against S-100 antigen in ultralow doses (Proproten-100) on acquisition of avoidance response in rats

We studied the effect of potentiated antibodies against S-100 antigen on learning of avoidance responses of 2 types. Peroral administration of antibodies promoted inhibition of locomotor activity and feeding behavior, which was associated with electrical pain stimulation. Our results indicate that the preparation in ultralow doses modulates the mechanism of memory formation.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 12, pp. 629–631, December, 2004This revised version was published online in April 2005 with a corrected cover date.