Hyperreactivity, muricide, and intraspecific aggression in the rat produced by infusion of local anesthetic into the lateral septum or surrounding areas

Intracranial infusions of a local anesthetic (lidocaine, 2%) were made bilaterally (4 microliter over 20 min) through permanently implanted cannulas ending in the lateral septum or adjacent areas. Increases in irritability and reactivity to the experimenter, muricide, and intermale aggression were produced by injections into the lateral septum and the region ventral to it. The increases in reactivity and interanimal aggresion occurred in varying degrees and were independent of one another, but intermale aggression occurred only in animals showing muricide. The most effective site for eliciting the entire spectrum of aggressive behaviors was the region ventral to the anterior septum. The region ventral to the posterior septum (medial preoptic area, anterior hypothalamic area, straia terminalis) was unique in that it tended to produce a high incidence of muricide, with only modest increases in reactivity. The lateral septum was moderately effective in producing the entire range of aggressive behaviors. No changes in behavior were noted with infusions into the medial septum or th medial forebrain bundle/lateral preoptic area ventrolateral to the septum. It is suggested that the hyperreactivity and irritability may be relat to hyperdefensiveness and that muricide and intermale aggression are points on a continuum of interanimal aggressiveness.     

Mouse killing by rats: Suppression by electrical stimulation ventral to the anterior septum

Killing of mice was suppressed in 18 out of 24 rats by electrical stimulation of the region ventral to the anterior septum lying between the vertical arm of the diagonal band of Broca and the rostral limb of the anterior commissure. The mean effective minimum stimulation intensity was 8.2 uA (60 HZ, RMS). Stimulation of the cingulate cortex did not suppress mouse killing (mean stimulus intensity: 38.7 uA). Electrical recordings revealed after discharge in response to the stimulation in only one animal. At the stimulation intensity which suppressed mouse killing, there was no significant suppression of eating in 6 of 9 animals tested. These results are consistent with other evidence implicating the region ventral to the anterior septum in the modulation of mouse killing in the rat.     

Reactivity and aggression in the rat: induction by alpha-adrenergic blocking agents injected ventral to anterior septum but not into lateral septum.

Intracranial injections were made bilaterally through permanently implanted cannulas ending in the lateral septum or in the region ventral to the anterior septum. The rats were first screened with injections of a local anesthetic, lidocaine, which blocks both synaptic and axonal conduction. Those animals that showed an increase in reactivity and aggression were then injected with a synaptic transmitter blocking agent. The results showed that transmitter blocking agents reproduced the effect of the local anesthetic only in the region ventral to the anterior septum and that alpha-adrenergic (phentolamine, tolazoline), but not beta-adrenergic (propranolol, hydralazine), cholinergic (atropine, hyocine), or dopaminergic (haloperidol) blocking agents were effective. These results suggest that synapses in the forebrain system controlling reactivity and aggression are alpha-asrenergic and are located in the region ventral to the anterior septum just lateral to the diagonal band of Broca. The septum itself may be involved only to the extent that it is traversed by fibers of passage.     

Personality from a controlled processing perspective: An fMRI study of neuroticism,extraversion, and self-consciousness

Although neuroticism has been central to most theories of personality, self-reported neuroticism has had limited success in predicting expected behavioral outcomes. The reason for this may be due, in part, to the imprecision of self-reports. The purpose of this study was to examine the relationship between neural correlates of control systems and neuroticism, extraversion, and self-consciousness. In response to an oddball task, neuroticism was associated with increased dorsal anterior cingulate cortex (dACC) reactivity, typically associated with discrepancy detection, whereas extraversion and self-consciousness were associated with lateral and medial frontoparietal networks, respectively, typically associated with task-focused (lateral) or self-focused (medial) controlled processes. We also examined whether the neural measure of neuroticism would predict a relevant behavioral outcome better than self-reports would. Interoceptive accuracy, an outcome associated with neuroticism, was better accounted for by dACC reactivity (r ²=.74) than by self-reported neuroticism (r ²=.16), suggesting that neural reactivities may provide a more direct measure of personality than self-reports do.     

Effects of d- versus l-amphetamine, food deprivation, and current intensity on self-stimulation of the lateral hypothalamus, substantia nigra, and medial frontal cortex of the rat.

Intracranial sefl-stimulation (ICSS) was studied in rats with chronically implanted lateral hypothalamic, substantia nigra, or medial frontal cortex bipolar electrodes. A comparison of the effects of d- and l-amphetamine on ICSS response rate indicated that the d isomer had a greater facilitatory effect than the l isomer at lateral hypothalamic and substantia nigra electrode sites but that neither isomer significantly affected medial frontal cortex ICSS. d-Amphetamine resulted in a dose-related increase in motor activity, but the same doses of the l isomer resulted in decreased motor activity. Only lateral hypothalamic ICSS response rates increased significantly in response to food deprivation. Increases in current intensity above the level used for amphetamine and food-deprivation testing facilitated lateral hypothalamic and substantia nigra ICSS response rates but did not significantly affect medial frontal cortex response rates. The responsiveness of ICSS at each electrode site appeared to be correlated with the fiber- and cell-body densities of catecholaminergic systems in the brain.     

Delta-sleep inducing peptide (DSIP) and ACTH (4-10) analogue influence fos-induction in the limbic structures of the rat brain under emotional stress

The effects of the ACTH (4-10) analogue, ACTH (4-7)-Pro-Gly-Pro, and delta-sleep inducing peptide (DSIP) on the induction of Fos immunoreactivity in the hypothalamic parvocellular paraventricular nucleus (pPVN) and limbic brain regions were studied in Wistar rats with high (resistant) or low (predisposed) resistance to emotional stress, predicted from differences in their open-field behaviour. Fos-immunoreactive (Fos-IR) cells were counted in brain sections automatically with a computer-based image analyser. Under basal conditions, Fos-IR cell numbers were greater in the pPVN in the predisposed rats, but were lower than in the resistant rats in the basolateral amygdala and medial and lateral septum. Intraperitoneal DSIP injection (30 μg/kg) increased basal Fos-IR cell number in the pPVN and lateral septum in resistant rats, with no effects in predisposed rats. ACTH (4-10) analogue (50 μg/kg)increased Fos expression in the pPVN in both resistant and predisposed rats, with essentially no effects in the basolateral amygdala or medial and lateral septum. Emotional stress (60 min restraint and intermittent subcutaneous electrical shocks) increased Fos expression in the pPVN and medial and lateral septum similarly in predisposed and resistant rats, but in the basolateral amygdala in only the predisposed rats. Intraperitoneal DSIP injection reduced the increases in Fos-IR cell number after emotional stress, particularly in predisposed rats. In predisposed rats DSIP decreased the number of Fos-IR cells in the pPVN and the medial and lateral septum, with no change in the basolateral amygdala. In resistant rats, DSIP decreased Fos expression only in the lateral septum. ACTH (4-10) analogue injection inhibited stress-induced Fos expression in the pPVN and the medial septum, but only in predisposed rats. The experiments indicate that DSIP and ACTH (4-10) analogue reduce pPVN and limbic neurone responses to emotional stress in the rats predisposed to emotional stress; the effects on Fos expression may play a role in the biological activities of these peptides.     

Bilaterally recorded multiple-unit activity of the cingulate cortex during head turning conditioning with unilateral medial forebrain bundle stimulation

Cats were conditioned to turn their heads using a tone conditioned stimulus (CS) and medial forebrain bundle stimulation (MFB) unconditioned stimulus (US). The CS+ was delivered to one ear at a time, in random order, followed by the US. A tone of a different frequency was used as a CS-. The cats learned to respond differentially to the CSs showing head movements of greater acceleration to the CS+ than CS- over sessions. Bilateral recordings of cingulate cortex multiple-unit activity showed increased response amplitudes over sessions and larger responses in the hemisphere ipsilateral to the US. Since ipsilateral multiple-unit responses did not differ for the CSs, the asymmetry was probably due to the sensitizing effect of the unilateral US. Although increases in cingulate cortex neural activity coincided with increases in conditioned head movements, larger activation of the cingulate cortex ipsilateral to the US suggests that the neural changes were independent of these movements.     

Time-dependent sequential increases in [14C]2-deoxyglucose uptake in subcortical and cortical structures during memory consolidation of an operant training in mice.

Previous results have suggested that memory processing may involve the sequential activation of subcortical and cortical structures. To study this phenomenon, we have examined the immediate (15 min) and delayed (220 min) metabolic changes produced in BALB/c mice by a partial training session in a bar-pressing appetitive task, using the [14C]-2-deoxyglucose (2-DG) relative glucose uptake method. These relative metabolic changes were compared to the ones produced in several control groups: untrained animals, sham-conditioned animals, overtrained animals, and animals forced to walk on a moving belt (immediate and delayed condition). Animals were given a single intrajugular injection (5 microCi) of 2-DG either 5 min before or 3 h (delayed condition) after the second training session. Forty minutes after the 2-DG injection, the animals were sacrificed and their brains processed for autoradiography. At the 15-min delay, a large 2-DG labeling increase was found in partially trained animals for various subcortical areas (septum, diagonal band, hippocampus, thalamus, and mammillary bodies) while a much smaller increase was found in four cortical areas (frontal, cingulate, parietal, and sensory motor cortices). At the 220-min delay, we observed a large 2-DG labeling increase in cortical (frontal, pyriform, and cingulate cortices) and subicular areas while a moderate 2-DG labeling increase was observed in entorhinal cortex and the diagonal band. These results show that, shortly after training, subcortical structures are preferentially activated while cortical structures are much less activated. Three hours later, at a time when retention performances have been shown to improve spontaneously in the same strain of mice and in the same task, cortical structures are highly activated.     

Differential effects of post-training muscimol and AP5 infusions into different regions of the cingulate cortex on retention for inhibitory avoidance in rats.

Adult male Wistar rats were bilaterally implanted with indwelling cannulae in four different coordinates of the cingulate cortex: (1) the anterior cingulate (AC), (2) the rostral region of the posterior cingulate (RC), (3) the upper portion of the caudal region of the posterior cingulate (UC), and (4) the lower portion of the caudal region of the posterior cingulate (LC). After recovery, animals were trained in a step-down inhibitory avoidance task (3.0-s, 0.4-mA foot shock). Either immediately, or 90 or 180 min after training, animals received a 0.5-microl infusion of vehicle (phosphate buffer, pH 7.4), of muscimol (0.5 microg), or of AP5 (5.0 microg). Retention testing was carried out 24 h after training. Muscimol was amnestic when given into any of the three coordinates of the posterior cingulate cortex 90 min after training, and when given into LC immediately post-training. In addition, AP5 was amnestic when given into UC 90 min post-training, but not when given into any other region and/or at any other time. None of the treatments had any effect when given into AC. The results suggest that memory processing of the inhibitory avoidance task is regulated by the posterior but not by the anterior cingulate cortex, through muscimol-sensitive synapses, relatively late after training. AP5-sensitive synapses appear to play a very limited role in these processes, restricted to UC.     

Serotonin's influence on predatory behavior of highly aggressive cba and weakly aggressive DD strains of mice

The effects of serotonin were studied on locust-killing behavior of mice from low (DD) and high (CBA) predatory aggressive strains. 5-HTP injected intraperitoneally (50 and 100 mg/kg) or 5-HT administered into the lateral ventricle (10 μg) significantly reduced locust-killing behavior in highly aggressive CBA mice. Imipramine (20, 30, and 40 mg/kg) elicited a dose-dependent inhibitory effect on predatory behavior. Fluoxetine (10 and 20 mg/kg) alone had a slight influence on locust-killing behavior but potentiated the action of the subthreshold dose of 5-HTP (25 mg/kg). Pretreatment with the blocker of 5-HT₂ type receptors methysergide (2 mg/kg) abolished the inhibitory effect of 5-HTP. These finding indicate that serotonin of the brain exerts an inhibitory effect on predatory behavior in mice. In contrast, neither lesion of the dorsal raphe nucleus (although significantly depleting the brain serotonin) nor treatment with methysergide (2 mg/kg) induced locust-killing behavior in weakly aggressive DD mice. Low predatory aggressiveness in DD mice is suggested to be related to the low tonus of the mechanisms activating killing behavior rather than to excessive serotonergic inhibitory influences.     

Neural correlates of rumination in depression

Rumination, or recursive self-focused thinking, has important implications for understanding the development and maintenance of depressive episodes. Rumination is associated with the worsening of negative mood states, greater affective responding to negative material, and increased access to negative memories. The present study was designed to use fMRI to examine neural aspects of rumination in depressed and healthy control individuals. We used a rumination induction task to assess differences in patterns of neural activation during ruminative self-focus as compared with a concrete distraction condition and with a novel abstract distraction condition in 14 participants who were diagnosed with major depressive disorder and 14 healthy control participants. Depressed participants exhibited increased activation in the orbitofrontal cortex, subgenual anterior cingulate, and dorsolateral prefrontal cortex as compared with healthy controls during rumination versus concrete distraction. Neural activity during rumination versus abstract distraction was greater for depressed than for control participants in the amygdala, rostral anterior cingulate/medial prefrontal cortex, dorsolateral prefrontal cortex, posterior cingulate, and parahippocampus. These findings indicate that ruminative self-focus is associated with enhanced recruitment of limbic and medial and dorsolateral prefrontal regions in depression. Supplemental materials for this article may be downloaded from http://cabn.psychonomic-journals.org/content/supplemental.     

Beyond the FN: A spatio-temporal analysis of the neural correlates of feedback processing in a virtual Blackjack game

Studies using event-related brain potentials (ERPs) to examine feedback processing in gambling tasks have focused almost exclusively on components elicited between 200 and 500 ms after feedback over the frontal-central region of the scalp (i.e., P2, feedback negativity (FN), and P3a). In contrast, studies examining the functional neuroanatomy of feedback processing reveal activation in a distributed network that includes the anterior and posterior cingulate, the lateral and medial orbitofrontal cortex, the occipital cortex, and the basal ganglia. In the current study, we used ERPs in combination with spatial principal components-massive univariate analysis and distributed source analysis to examine the time course, topography, and neural generators of ERPs elicited in a virtual Blackjack game from 0 to 2000 ms after feedback was delivered. The ERP data revealed the P2–FN–P3a complex, as well as, broadly distributed transient and slow wave activity that was sensitive to the magnitude and valence of an outcome. The ERPs reflected activation in the anterior and posterior cingulate, in addition to the occipital, temporal and medial frontal cortices. These data demonstrate that ERPs can provide valuable insight into the timing of neural recruitment within a distributed cortical network during the first two seconds of feedback processing.     

Effects of daily and acute restraint stress during lactation on maternal aggression and behavior in mice

A decreased reactivity to stressors during lactation might heighten the expression of maternal care (including defense of offspring) by minimizing the extent to which stress can impact maternal care. Although stressors applied during pregnancy have variable effects on maternal aggression (or defense of offspring), to date no study has examined the effects of stress applied during the postpartum period on maternal aggression. In this study, we examined the effects of both daily and acute restraint stress (30 min) applied postpartum on maternal aggression and other maternal behaviors. Daily restraint (ending 2 h before testing) did not alter any measure of maternal behavior, including nursing, licking and grooming of pups and pup retrieval, or any measure of maternal aggression. In contrast, acute stress significantly impaired total time aggressive and number of attacks, but pup retrieval was normal. c-Fos levels were significantly elevated in a number of brain regions in association with acute stress, including lateral septum (LS), caudal periaqueductal gray and medial amygdala (MeA), suggesting possible sites where stress reactivity could alter aggression. Together, the results indicate that acute restraint stress impairs maternal aggression and provide a starting point for future studies examining how stress reactivity pathways may intersect with maternal aggression pathways.     

Neural Correlates of Emotional Reactivity in Sensation Seeking

ABSTRACT— High sensation seeking has been linked to increased risk for drug abuse and other negative behavioral outcomes. This study explored the neurobiological basis of this personality trait using functional magnetic resonance imaging (fMRI). High sensation seekers (HSSs) and low sensation seekers (LSSs) viewed high- and low-arousal pictures. Comparison of the groups revealed that HSSs showed stronger fMRI responses to high-arousal stimuli in brain regions associated with arousal and reinforcement (right insula, posterior medial orbitofrontal cortex), whereas LSSs showed greater activation and earlier onset of fMRI responses to high-arousal stimuli in regions involved in emotional regulation (anterior medial orbitofrontal cortex, anterior cingulate). Furthermore, fMRI response in anterior medial orbitofrontal cortex and anterior cingulate was negatively correlated with urgency. Finally, LSSs showed greater sensitivity to the valence of the stimuli than did HSSs. These distinct neurobiological profiles suggest that HSSs exhibit neural responses consistent with an overactive approach system, whereas LSSs exhibit responses consistent with a stronger inhibitory system.     

用药动作线索诱发海洛因戒断者的镜像神经活动:一项fMRI研究

相关线索能够诱发药物依赖者的心理渴求,而健康人不会对相关线索产生心理渴求。15名海洛因成瘾者和12名没有任何物质滥用的健康被试参与实验,收集了他们在观看相关线索与对照线索时的脑神经活动。结果发现,药物线索能够诱发戒断者更多脑区的活动,包括扣带回和楔前叶。两组被试在对照动作线索刺激诱发作用下,其颞叶、顶叶均出现了较为一致的活动。在用药动作线索诱发作用下,戒断组双侧颞中回、双侧顶下小叶、左侧顶上小叶和右侧额下回显示出显著活动,并且与对照动作线索激活脑区一致;健康组被试除枕叶-颞叶联合区外,没有出现显著的脑区活动。以上结果表明,用药动作线索诱发了海洛因戒断者颞中回、顶下小叶、额下回等镜像神经系统的活动,这些脑区对不同类型的相关线索十分敏感,它们可能通过对用药动作的心理模拟,参与了用药动作线索的快速自动化加工。     

寻找自我:基于认知神经的观点

默认网络相关研究表明,生物进化的社会适应性建构了自我的认知神经基础,与James的自我结构相对应:主我位于后部扣带回,精神自我位于内侧前额叶,身体自我位于顶下小叶和脑岛; 并且与内侧前额叶、顶下小叶和后部扣带回之间的信息传递相关。个体在基线水平的大脑活动表明,自我是通过后部扣带回接收并调节全脑(包括表征客我的脑区)信息流,随时准备将外界满足需要有利于个体生存的资源纳入其中的神经系统。对于探讨“认识自我”这个古老的哲学问题与现代认知神经科学之间的关系有重要意义。     

Strength of default mode resting-state connectivity relates to white matter integrity in children

A default mode network of brain regions is known to demonstrate coordinated activity during the resting state. While the default mode network is well characterized in adults, few investigations have focused upon its development. We scanned 9-13-year-old children with diffusion tensor imaging and resting-state functional magnetic resonance imaging. We identified resting-state networks using Independent Component Analysis and tested whether the functional connectivity between the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) depends upon the maturation of the underlying cingulum white matter tract. To determine the generalizability of this relationship, we also tested whether functional connectivity depends on white matter maturity between bilateral lateral prefrontal cortex (lateral PFC) within the executive control network. We found a positive relationship between mPFC-PCC connectivity and fractional anisotropy of the cingulum bundle; this positive relationship was moderated by the age of the subjects such that it was stronger in older children. By contrast, no such structure-function relationship emerged between right and left lateral PFC. However, functional and structural connectivity of this tract related positively with cognitive speed, fluency, and set-switching neuropsychological measures.     

Medial prefrontal cortex lesions abolish contextual control of competing responses

There is much debate as to the extent and nature of functional specialization within the different subregions of the prefrontal cortex. The current study was undertaken to investigate the effect of damage to medial prefrontal cortex subregions in the rat. Rats were trained on two biconditional discrimination tasks, one auditory and one visual, in two different contexts. At test, they received presentations of audiovisual compounds of these training stimuli in extinction. These compounds had dictated either the same (congruent trials) or different (incongruent trials) responses during training. In sham-operated controls, contextual cues came to control responding to conflicting information provided by incongruent stimulus compounds. Experiment 1 demonstrated that this contextual control of responding was not evident in individual rats with large amounts of damage that included the prelimbic and cingulate subregions of the prefrontal cortex. Experiment 2 further dissociated the result of Experiment 1, demonstrating that lesions specific to the anterior cingulate cortex were sufficient to produce a deficit early on during presentation of an incongruent stimulus compound but that performance was unimpaired as presentation progressed. This early deficit suggests a role for the anterior cingulate cortex in the detection of response conflict, and for the medial prefrontal cortex in the contextual control of competing responses, providing evidence for functional specialization within the rat prefrontal cortex.     

Approach and withdrawal analysis of the effects of hypothalamic stimulation and lesions in rats.

In a paradigm in which rats would both initiate and terminate hypothalamic stimulation, "purely" rewarding lateral hypothalamic and "purely" aversive medial hypothalamic electrodes were identified. Subjects were then given a series of tests designed to assess the effects of brain stimulation on approach and withdrawal behaviors. Lateral hypothalamic stimulation facilitated approach behavior and suppressed withdrawal behaviors, whereas medial hypothalamic stimulation produced largely the opposite effects. No serious motor deficits due to stimulation were detected with either type of electrode. In a second experiment, the approach-withdrawal effects of bilateral lateral hypothalamic lesions were tested and found to suppress approach behaviors and facilitate withdrawal behaviors. Other neurological examinations revealed motor deficits, but these deficits do not account for the specific pattern of results observed on the approach-withdrawal tests. These approach-withdrawal phenomena are interpreted in terms of altering a natural balance between approach and withdrawl behavior facilitating systems in the lateral and medial hypothalamus, respectively.     

Bi-hemispheric engagement in the retrieval of autobiographical episodes

Functional magnetic resonance imaging (fMRI) was used to study the neural correlates of neutral, stressful, negative and positive autobiographical memories. The brain activity produced by these different kinds of episodic memory did not differ significantly, but a common pattern of activation for different kinds of autobiographical memory was revealed that included (1) largely bilateral portions of the medial and superior temporal lobes, hippocampus and parahippocampus, (2) portions of the ventral, medial, superior and dorsolateral prefrontal cortex, (3) the anterior and posterior cingulate, including the retrosplenial, cortex, (4) the parietal cortex, and (5) portions of the cerebellum. The brain regions that were mainly activated constituted an interactive network of temporal and prefrontal areas associated with structures of the extended limbic system. The main bilateral activations with left-sided preponderance probably reflected reactivation of complex semantic and episodic self-related information representations that included previously experienced contexts. In conclusion, the earlier view of a strict left versus right prefrontal laterality in the retrieval of semantic as opposed to episodic autobiographical memory, may have to be modified by considering contextual variables such as task demands and subject variables. Consequently, autobiographical memory integration should be viewed as based on distributed bi-hemispheric neural networks supporting multi-modal, emotionally coloured components of personal episodes.