Neurochemical mechanisms underlying amygdaloid modulation of aggressive behavior in the cat

Studies designed to determine the respective roles of substance P, excitatory amino acids, and enkephalins in amygdaloid modulation of defensive rage behavior in the cat are presented. The basic design of these studies involved three stages. In stage I, cannula electrodes for stimulation and drug infusion were implanted into medial hypothalamic or midbrain periaqueductal gray (PAG) sites from which defensive rage behavior could be elicited. Then, a stimulating electrode was implanted into a site within the medial, basal, or central nuclear complex from which modulation of the defensive rage response could be obtained. Amygdaloid modulation of defensive rage was determined in the following manner: it employed the paradigm of dual stimulation in which comparisons were made of response latencies between alternate trials of dual (i. e., amygdala = medial hypothalamus [or PAG]) and single stimulation of the hypothalamus or PAG alone. Thus, stage I established the baseline level ofmodulation (i. e., facilitation or suppression of defensive rage) in the predrug stimulation period. In stage II, a selective or nonselective receptor antagonist for a given transmitter system was administered either peripherally or intracerebrally at the defensive rage site, after which time the same dual stimulation paradigm was then repeated over the ensuing 180 min postinjection period in order to determine the effects of drug delivery upon amygdaloid modulation of defensive rage. Stage III of the study took place at the completion of the pharmacological testing phase. The retrograde axonal tracer, Fluoro-Gold, was microinjected into the defensive rage site within the medial hypothalamus or PAG, and following a 6-14 day survival period, animals were sacrificed and brains were processed for histological and immunocytochemical analyses for the neurotransmitters noted above. This procedure thus permitted identification of cells within the amygdala which were labeled retrogradely and which were also immunostained positively for substance P, excitatory amino acids, or enkephalin. For studies involving substance P, defensive rage was elicited from the medial hypothalamus and for studies examining the roles of excitatory amino acids and enkephalin, defensive rage was elicited from the PAG. In the first study, facilitation of hypothalamically elicited defensive rage was obtained with dual stimulation of the medial nucleus of the amygdala. In separate experiments, the selective NK₁ non-peptide antagonist, CP 96,345, was administered both peripherally as well as intracerebrally into the hypothalamic defensive rage sites in doses of 0.5-4.0 mg/kg (i. p.) and 0.5-2.5 nmol (i. c.). Following drug delivery, the facilitatory effects of medial amygdaloid stimulation were blocked in a dose- and time-dependent manner in which the effects were noted as early as 5 min postinjection. The maximum drug dose (4.0 mg/kg) employed for peripheral administration resulted in a 42% reduction in the facilitatory effects of the medical amygdala (P < 0.002). This drug, when microinjected directly into medial hypothalamic defensive rage sites at the maximum dose level of 2.5 nmol, resulted in an 84% reduction of the suppressive effects of amygdaloid stimulation (P < 0.5) at 5 min postinjection. In the next study, an N-methyl-D-aspartate (NMDA) antagonist, DL-α-amino-7-phosphonoheptanoic acid (AP-7), was administered either peripherally (0.1-1.0 mg/kg) or intracerebrally (0.2 and 2.0 nmol) into PAG defensive rage sites. Facilitation of defensive rage behavior, which was observed following dual stimulation of the basal amygdala and PAG, was significantly reduced by either route of drug administration in a dose- and time-dependent manner. At the maximum dose level of peripheral administration, AP-7 reduced amygdaloid facilitation of defensive rage by 63% (P < 0.001) for 60 min, postinjection. A smaller (i. e., 19%) but still significant (P < 0.05) reduction in facilitation was obtained following intracerebral administration of the drug. In a third study, the non-selective opioid receptor antagonist, naloxone (27.5 nmol), infused directly into PAG defensive rage sites, totally blocked the suppressive effects of central amygdaloid stimulation for a period of 30 min (P < 0.05) in a dose- and time-dependent manner. The anatomical phase of this study revealed the following relationships: 1) that large numbers of neurons projecting to the medial hypothalamus from the medial amygdala immunoreact positively for substance P; 2) that neurons projecting to the PAG from the basal complex of amygdala immunoreact positively for glutamate and aspartate; and 3) that neurons located within the central nucleus of the amygdala which project to the PAG immunoreact positively for met-enkephalin. Collectively, these observations provide new evidence which characterizes the likely neurotransmitters linked with specific amygdaloid pathways subserving the modulation of defensive rage behavior in the cat.     

Directional interaction of midbrain and hypothalamus in the control of carbachol-induced aggression

Microinjection of carbachol into the ventromedial part of the anterior hypothalamus or the ventrolateral part of the mesencephalic central gray elicits affective aggression in the cat. Pretreatment with atropine in the same site blocks carbachol-induced aggression. Prior administration of atropine into the midbrain blocks aggression induced by carbachol injections into the hypothalamus, but atropine injected into the hypothalamus does not prevent affective aggression elicited by carbachol administered into the midbrain. The results demonstrate a directional interaction between midbrain and hypothalamus, and provide suggestive evidence for a hierarchal organization of these limbic structures in the control of cholinergically-mediated affective aggression.     

相继记忆模式：展现情节记忆形成脑机制的窗口

相继记忆模式在记忆形成的脑认知成像研究领域应用广泛,已成为研究者探究大脑形成记忆时活动的主要窗口。该文在介绍相继记忆模式及记忆形成过程的基础上,分析影响相继记忆效应大小和时空分布的因素,最后讨论内侧颞叶及前额叶神经网络中相关脑区如何分工、协同支持情节记忆形成。情节记忆多维度特性导致该神经网络中有关区域表现出不同形式的相继记忆效应,因此,该文提出有效分离这些脑区在记忆形成中如何分工及交互协同关系进行更为重要     

Attention, emotion, and deactivation of default activity in inferior medial prefrontal cortex

Attention deactivates the inferior medial prefrontal cortex (IMPC), but it is uncertain if emotions can attenuate this deactivation. To test the extent to which common emotions interfere with attention, we measured changes of a blood flow index of brain activity in key areas of the IMPC with positron emission tomography (PET) of labeled water (H(15)2O) uptake in brain of 14 healthy subjects. The subjects performed either a less demanding or a more demanding task of attention while they watched neutral and emotive images of people in realistic indoor or outdoor situations. In the less demanding task, subjects used the index finger to press any key when a new image appeared. In the more demanding task, subjects chose the index or middle finger to press separate keys for outdoor and indoor scenes. Compared to the less demanding task, in a global search of all gray matter, the more demanding significantly lowered blood flow (rCBF) in left IMPC, left and right insula, and right amygdala, and significantly raised blood flow in motor cortex and right precuneus. Restricted searches of rCBF changes by emotion, at coordinates of significant effect in previous studies of the medial prefrontal and temporal cortices, revealed significant activation in the fusiform gyrus, independently of the task. In contrast, we found no effect of emotional content in the IMPC, where emotions failed to override the effect of the task. The results are consistent with a role of the IMPC in the selection among competitive inputs from multiple brain regions, as predicted by the theory of a default mode of brain function. The absent emotional interference with the deactivation of the default state suggests that the inferior prefrontal cortex continued to serve the attention rather than submit to the distraction.     

Learning related modulation of functional retrieval networks in man

The medial temporal lobe has been implicated in studies of episodic memory tasks involving spatio-temporal context and object-location conjunctions. We have previously demonstrated that an increased level of practice in a free-recall task parallels a decrease in the functional activity of several brain regions, including the medial temporal lobe, the prefrontal, the anterior cingulate, the anterior insular, and the posterior parietal cortices, that in concert demonstrate a move from elaborate controlled processing towards a higher degree of automaticity. Here we report data from two experiments that extend these initial observations. We used a similar experimental approach but probed for effects of retrieval paradigms and stimulus material. In the first experiment we investigated practice related changes during recognition of object-location conjunctions and in the second during free-recall of pseudo-words. Learning in a neural network is a dynamic consequence of information processing and network plasticity. The present and previous PET results indicate that practice can induce a learning related functional restructuring of information processing. Different adaptive processes likely subserve the functional re-organisation observed. These may in part be related to different demands for attentional and working memory processing. It appears that the role(s) of the prefrontal cortex and the medial temporal lobe in memory retrieval are complex, perhaps reflecting several different interacting processes or cognitive components. We suggest that an integrative interactive perspective on the role of the prefrontal and medial temporal lobe is necessary for an understanding of the processing significance of these regions in learning and memory. It appears necessary to develop elaborated and explicit computational models for prefrontal and medial temporal functions in order to derive detailed empirical predictions, and in combination with an efficient use and development of functional neuroimaging approaches, to further the understanding of the processing significance of these regions in memory.     

内侧前额叶皮质—— “自我”的神经基础

自我神经基础的探讨常基于自我相关加工的研究, 涉及皮质中线结构各个脑区甚至全脑协同作用。内侧前额叶皮质及其次成分在自我相关加工中发挥重要作用：腹内侧前额叶皮质较多支持默认模式下的自我加工、自我信息的觉察和“在线”自我加工, 背内侧前额叶皮质主要参与有意识的自我参照加工、自我信息的评价和“主导的”自我加工。在自我-他人表征中, 自我-他人表征的情感性、认知性和文化性因素均调节内侧前额叶皮质及次成分的活动。未来在动态的时间和人际背景中解析自我加工的神经机制是重要的研究方向。     

The minimal self hypothesis

For millennia self has been conjectured to be necessary for consciousness. But scant empirical evidence has been adduced to support this hypothesis. Inconsistent explications of “self” and failure to design apt experiments have impeded progress. Advocates of phenomenological psychiatry, however, have helped explicate “self,” and employed it to explain some psychopathological symptoms. In those studies, “self” is understood in a minimalist sense, sheer “for-me-ness.” Unfortunately, explication of the “minimal self” (MS) has relied on conceptual analysis, and applications to psychopathology have been hermeneutic, allowing for many degrees of interpretive latitude. The result is that MS’s current scientific status is analogous to that of the “atom,” at the time when “atom” was just beginning to undergo transformation from a philosophical to a scientific concept. Fortunately, there is now an opportunity to promote a similar transformation for “MS.” Discovery of the brain’s Default Mode Network (DMN) opened the door to neuroimaging investigations of self. Taking the DMN and other forms of intrinsic activity as a starting point, an empirical foothold can be established, one that spurs experimental research and that enables extension of research into multiple phenomena. New experimental protocols that posit “MS” can help explain phenomena hitherto not thought to be related to self, thereby hastening development of a mature science of self. In particular, targeting phenomena wherein consciousness is lost and recovered, as in some cases of Unresponsive Wakefulness Syndrome (UWS), allow for design of neuroimaging probes that enable detection of MS during non-conscious states. These probes, as well as other experimental protocols applied to NREM Sleep, General Anesthesia (GA), and the waking state, provide some evidence to suggest that not only can self and consciousness dissociate, MS might be a necessary precondition for conscious experience. Finally, these findings have implications for the science of consciousness: it has been suggested that “levels of consciousness” (LoC) is not a legitimate concept for the science of consciousness. But because we have the conceptual and methodological tools with which to refine investigations of MS, we have the means to identify a possible foundation—a bifurcation point—for consciousness, as well as the means by which to measure degrees of distance from that foundation. These neuroimaging investigations of MS position us to better assess whether LoC has a role to play in a mature science of consciousness.