Differential effects of inferior temporal cortex lesions upon visual and auditory-evoked potentials in the amygdala of the squirrel monkey (Saimiri sciureus)

Visual-evoked potentials (VEPs) and auditory-evoked potentials (AEPs) were elicited from amygdala nuclei and inferior temporal (IT) cortex in chaired, alert squirrel monkeys to diffuse flash and click stimuli. VEPs were recorded from electrodes placed in basalis lateralis amygdalae (BLA) and basalis medialis amygdalae (BMA) while AEPs could also be obtained from additional electrode sites in basalis accessorius medialis (BAM), centralis amygdalae (CeA), and lateralis amygdalae (LA). The amygdala-evoked potentials resulting from stimulation of the two modalities were similar in terms of component configuration. AEPs recorded from the IT cortex had shorter latencies than the amygdala VEPs that were recorded. Both modalities of stimulation elicited potentials with shorter onset latencies in the amygdala than those recorded from the surface of IT cortex. Bilateral ablation of the IT cortex eliminated VEPs recorded from the BMA but not the BLA amygdala region. AEPs recorded from BMA as well as other amygdala areas were not consistently affected by these IT cortical ablations.     

Perseverative interference with object-in-place scene learning in rhesus monkeys with bilateral ablation of ventrolateral prefrontal cortex

Surgical disconnection of the frontal cortex and inferotemporal cortex severely impairs many aspects of visual learning and memory, including learning of new object-in-place scene memory problems, a monkey model of episodic memory. As part of a study of specialization within prefrontal cortex in visual learning and memory, we tested monkeys with bilateral ablations of ventrolateral prefrontal cortex in object-in-place scene learning. These monkeys were mildly impaired in scene learning relative to their own preoperative performance, similar in severity to that of monkeys with bilateral ablation of orbital prefrontal cortex. An analysis of response types showed that the monkeys with lesions were specifically impaired in responding to negative feedback during learning: The post-operative increase in errors was limited to trials in which the first response to each new problem, made on the basis of trial and error, was incorrect. This perseverative pattern of deficit was not observed in the same analysis of response types in monkeys with bilateral ablations of the orbital prefrontal cortex, who were equally impaired on trials with correct and incorrect first responses. This may represent a specific signature of ventrolateral prefrontal involvement in episodic learning and memory.     

Beyond arousal and valence: The importance of the biological versus social relevance of emotional stimuli

The present study addressed the hypothesis that emotional stimuli relevant to survival or reproduction (biologically emotional stimuli) automatically affect cognitive processing (e.g., attention, memory), while those relevant to social life (socially emotional stimuli) require elaborative processing to modulate attention and memory. Results of our behavioral studies showed that (1) biologically emotional images hold attention more strongly than do socially emotional images, (2) memory for biologically emotional images was enhanced even with limited cognitive resources, but (3) memory for socially emotional images was enhanced only when people had sufficient cognitive resources at encoding. Neither images’ subjective arousal nor their valence modulated these patterns. A subsequent functional magnetic resonance imaging study revealed that biologically emotional images induced stronger activity in the visual cortex and greater functional connectivity between the amygdala and visual cortex than did socially emotional images. These results suggest that the interconnection between the amygdala and visual cortex supports enhanced attention allocation to biological stimuli. In contrast, socially emotional images evoked greater activity in the medial prefrontal cortex (MPFC) and yielded stronger functional connectivity between the amygdala and MPFC than did biological images. Thus, it appears that emotional processing of social stimuli involves elaborative processing requiring frontal lobe activity.     

Editorial: Information Processing and the Emotional Disorders

Abstract

It is shown that emotions can usefully be considered as states produced by reinforcing stimuli. The ways in which a wide variety of emotions can be produced, and the functions of emotion, are considered. There is evidence that the amygdala is involved in the formation of stimulus-reinforcement associations, and the orbitofrontal cortex with correcting behavioural responses when these are no longer appropriate because previous reinforcement contingencies change. This evidence comes from the effects of damage to these structures, and from recording the activity of single neurons in these structures in the monkey during the formation and disconnection of stimulus-reinforcement associations. In so far as emotions can be defined as states produced by reinforcing stimuli, then the amygdala and orbitofrontal cortex are seen to be of great importance for emotions, in that they are involved respectively in the elicitation of learned emotional responses, and in the correction or adjustment of these emotional responses as the reinforcing value of environmental stimuli alters. One of the theses advanced is that the changes in emotional behaviour produced by damage to the brain can be analysed and understood by considering how different parts of it function in reinforcement and in the formation and disconnection of stimulus-reinforcement connections. Another thesis is that there is a population of neurons in the amygdala and parts of the temporal lobe visual cortex specialised to respond to faces, and that these neurons may be involved in social and emotional resposes to faces.

Some of the outputs of the amygdala and orbitofrontal cortex are directed to the hypothalamus, which not only provides one route for these reinforcing environmental events to produce autonomic responses, but also is implicated in the utilisation of such stimuli in motivational responses, such as feeding and drinking, and in emotional behaviour. Other outputs of the amygdala and orbitofrontal cortex which may enable them to influence behaviour are directed to the striatum, and also back towards some of the cortical regions from which they receive inputs. It is suggested that these latter projections are important in the effects which mood states have on cognitive processing.     

A model of amygdala–hippocampal–prefrontal interaction in fear conditioning and extinction in animals

Empirical research has shown that the amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC) are involved in fear conditioning. However, the functional contribution of each brain area and the nature of their interactions are not clearly understood. Here, we extend existing neural network models of the functional roles of the hippocampus in classical conditioning to include interactions with the amygdala and prefrontal cortex. We apply the model to fear conditioning, in which animals learn physiological (e.g. heart rate) and behavioral (e.g. freezing) responses to stimuli that have been paired with a highly aversive event (e.g. electrical shock). The key feature of our model is that learning of these conditioned responses in the central nucleus of the amygdala is modulated by two separate processes, one from basolateral amygdala and signaling a positive prediction error, and one from the vmPFC, via the intercalated cells of the amygdala, and signaling a negative prediction error. In addition, we propose that hippocampal input to both vmPFC and basolateral amygdala is essential for contextual modulation of fear acquisition and extinction. The model is sufficient to account for a body of data from various animal fear conditioning paradigms, including acquisition, extinction, reacquisition, and context specificity effects. Consistent with studies on lesioned animals, our model shows that damage to the vmPFC impairs extinction, while damage to the hippocampus impairs extinction in a different context (e.g., a different conditioning chamber from that used in initial training in animal experiments). We also discuss model limitations and predictions, including the effects of number of training trials on fear conditioning.     

The role of the amygdala in face perception and evaluation

Faces are one of the most significant social stimuli and the processes underlying face perception are at the intersection of cognition, affect, and motivation. Vision scientists have had a tremendous success of mapping the regions for perceptual analysis of faces in posterior cortex. Based on evidence from (a) single unit recording studies in monkeys and humans; (b) human functional localizer studies; and (c) meta-analyses of neuroimaging studies, I argue that faces automatically evoke responses not only in these regions but also in the amygdala. I also argue that (a) a key property of faces represented in the amygdala is their typicality; and (b) one of the functions of the amygdala is to bias attention to atypical faces, which are associated with higher uncertainty. This framework is consistent with a number of other amygdala findings not involving faces, suggesting a general account for the role of the amygdala in perception.     

Deficits in visual learning produced by posterior temporal lesions in cats

Eight cats with lesions in the posterior temporal (PT) cortex, seven cats with lesions in the basolateral amygdala (BLA), and eight intact controls were observed on eight tests of visual discrimination learning and of spontaneous responses to salient visual stimuli. The effects of the two lesions were somewhat dissociable. The PT lesions were accompanied by a severe deficit in pattern discrimination learning but no loss in visual tracking or orientation to the silhouette of a threatening cat. The BLA lesions produced a milder and less consistent loss in pattern discrimination but serious defects in tracking and reponse to the cat silhouette. Both operated groups performed well on the visual cliff. The deficit from PT lesions appeared independent of damage to the geniculocortical system. The parallel of symptoms from PT lesions in cats and inferotemporal lesions in monkeys is discussed.     

Impaired emotional declarative memory following unilateral amygdala damage

Case studies of patients with bilateral amygdala damage and functional imaging studies of normal individuals have demonstrated that the amygdala plays a critical role in encoding emotionally arousing stimuli into long-term declarative memory. However, several issues remain poorly understood: the separate roles of left and right amygdala, the time course over which the amygdala participates in memory consolidation, and the type of knowledge structures it helps consolidate. We investigated these questions in eight subjects with unilateral amygdala damage, using several different measures. For comparison, our main task used stimuli identical to those used previously to investigate emotional declarative memory in patients with bilateral amygdala damage. Contrasts with both brain-damaged and normal control groups showed that subjects with left amygdala damage were impaired in their memory for emotional stimuli, despite entirely normal memory for neutral stimuli (because of a number of caveats, the findings from subjects with right amygdala damage were less clear). Follow-up experiments suggested that the normal facilitation of memory for emotional stimuli may develop over an extended time course (>30 min), consistent with prior findings, and that the specific impairment we report may depend in part on the lexical nature of the task used (written questionnaire). We stress the complex and temporally extended nature of memory consolidation and suggest that the amygdala may influence specific components of this process.     

Time-discrimination performance in cats with lesions in prefrontal cortex and caudate nucleus.

Cats were trained on a time-discrimination task in which different periods of bodily confinement served as discriminanda for go-left/go-right responding. Lesions of gyrus proreus or the associated anteroventral part of nucleus caudatus impaired relearning in this situation. After reacquisition, animals with caudate lesions received proreal ablations and animals with cortical damage received caudate lesions; both additional lesions caused reappearance of the deficit. The absence of external stimuli to signal locus of reinforcement at the moment of spatial choice may have been crucial for eliciting the deficit. The data support the notion that the prefrontal cortex and the anatomically related part of the caudate nucleus participate in similar behaviors.     

Cognitive and Emotional Abnormalities in Systemic Lupus Erythematosus: Evidence for Amygdala Dysfunction

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disorder characterized by the production of autoantibodies. Approximately 30-50?% of patients produce autoantibodies directed against N-Methyl-D-aspartic acid receptors (NMDARs). Once they have gained access to brain tissue, these autoantibodies bind to the NR2A subunit of the NMDARs and synergize with glutamate to cause excitatory, non-inflammatory cell death or alter neuron function. Both humans with SLE and animal models of SLE have shown structural and functional damage to the amygdala. The amygdala is a brain region important for processing the emotional relevance of stimuli in the environment. It also serves to modulate perception, attention, and memory to facilitate the processing and learning of relevant stimuli. Research has linked amygdala damage to deficits in emotional memory and emotional behavior. Individuals with SLE often exhibit emotional dysregulation, such as lability and depression; however, the behavioral impact of possible amygdala dysfunction has yet to be studied in this population. The purpose of this review is to 1) examine possible associations between SLE, anti-NMDAR antibodies, amygdala damage, and emotional processing deficits and 2) to identify the clinical, social, and treatment implications for individuals with SLE who suffer from deficits in emotional processing.     

Social perception from visual cues: role of the STS region

Social perception refers to initial stages in the processing of information that culminates in the accurate analysis of the dispositions and intentions of other individuals. Single-cell recordings in monkeys, and neurophysiological and neuroimaging studies in humans, reveal that cerebral cortex in and near the superior temporal sulcus (STS) region is an important component of this perceptual system. In monkeys and humans, the STS region is activated by movements of the eyes, mouth, hands and body, suggesting that it is involved in analysis of biological motion. However, it is also activated by static images of the face and body, suggesting that it is sensitive to implied motion and more generally to stimuli that signal the actions of another individual. Subsequent analysis of socially relevant stimuli is carried out in the amygdala and orbitofrontal cortex, which supports a three-structure model proposed by Brothers. The homology of human and monkey areas involved in social perception, and the functional interrelationships between the STS region and the ventral face area, are unresolved issues.     

Amygdala response to mother

In altricial species, like the human, the caregiver, very often the mother, is one of the most potent stimuli during development. The distinction between mothers and other adults is learned early in life and results in numerous behaviors in the child, most notably mother-approach and stranger wariness. The current study examined the influence of the maternal stimulus on amygdala activity and related circuitry in 25 developing children (n = 13) and adolescents (n = 12), and how this circuitry was associated with attachment-related behaviors. Results indicated that maternal stimuli were especially effective in recruiting activity in the left dorsal amygdala, and activity in this amygdala region showed increased functional connectivity with evaluative and motor regions during viewing of maternal stimuli. Increases in this left dorsal amygdala activity and related amygdala-cortical functional connectivity were associated with increased mother-approach behaviors as measured by in-scanner behavioral responding and out-of-scanner child-report. Moreover, age-related changes in amygdala activity to strangers statistically mediated the developmentally typical decline in stranger wariness seen across this period. These results suggest that mother-induced behaviors are enacted by maternal influence on amygdala-cortical circuitry during childhood and adolescence.     

情绪加工的脑时空动态机制

本文综述了罗倩博士及其同事在近年来开展的情绪研究工作。他们通过认知行为和脑成像技术(包括fMRI、MEG), 系统考察了情绪刺激的自动化、优先加工的神经机制, 具体包括三个方面的研究内容：(1)阈下情绪加工(相对于阈上水平)的神经机制; (2)参与情绪加工的脑区之间的动态时空关系及功能联结; (3)情绪与注意之间的交互作用。     

Verbal and Nonverbal Emotional Memory Following Unilateral Amygdala Damage

The amygdala is involved in the normal facilitation of memory by emotion, but the separate contributions of the left and right amygdala to memory for verbal or nonverbal emotional material have not been investigated. Fourteen patients with damage to the medial temporal lobe including the amygdala (seven left, seven right), 18 brain-damaged, and 36 normal controls were exposed to emotional and neutral pictures accompanied by verbal narratives. Memory for both narratives and pictures was assessed with a free recall test 24 h later. Subjects with left amygdala damage failed to show the normally robust enhancement of memory for verbal and nonverbal emotional stimuli. The group with right amygdala damage showed the normal pattern of facilitation of memory by emotion for both verbal and nonverbal stimuli despite an overall reduction in memory performance. Furthermore, subjects with left amygdala damage were disproportionately impaired on memory for emotional narratives as compared with memory for emotional pictures. The latter finding offers partial support for a lateralized and material-specific pattern of the amygdala's contribution to emotional memory.     

Differential regulation of glutamic acid decarboxylase gene expression after extinction of a recent memory vs. intermediate memory

Extinction reduces fear to stimuli that were once associated with an aversive event by no longer coupling the stimulus with the aversive event. Extinction learning is supported by a network comprising the amygdala, hippocampus, and prefrontal cortex. Previous studies implicate a critical role of GABA in extinction learning, specifically the GAD65 isoform of the GABA synthesizing enzyme glutamic acid decarboxylase (GAD). However, a detailed analysis of changes in gene expression of GAD in the subregions comprising the extinction network has not been undertaken. Here, we report changes in gene expression of the GAD65 and GAD67 isoforms of GAD, as measured by relative quantitative real-time RT-PCR, in subregions of the amygdala, hippocampus, and prefrontal cortex 24-26 h after extinction of a recent (1-d) or intermediate (14-d) fear memory. Our results show that extinction of a recent memory induces a down-regulation of Gad65 gene expression in the hippocampus (CA1, dentate gyrus) and an up-regulation of Gad67 gene expression in the infralimbic cortex. Extinguishing an intermediate memory increased Gad65 gene expression in the central amygdala. These results indicate a differential regulation of Gad gene expression after extinction of a recent memory vs. intermediate memory.     

Working Memory for Temporal and Nontemporal Events in Monkeys

This is the first report that introduces appropriate behavioral tasks for monkeys for investigations of working memory for temporal and nontemporal events. Using several behavioral tests, the study also shows how temporal information is coded during retention intervals in the tasks. Each of three monkeys was trained with two working memory tasks: delayed matching-to-sample of stimulus duration (DMS-D) and delayed matching-to-sample of stimulus color (DMS-C). The two tasks employed an identical apparatus and responses and differed only in the temporal and nontemporal attribute of the stimuli to be retained for correct performance. When a retention interval between the sample and comparison stimuli was prolonged, the monkeys made more incorrect responses to short samples in the DMS-C task, suggesting “trace decay” of memory for short stimuli. However, the same monkeys showed no such increase in incorrect responses to short samples in the DMS-D task, suggesting active coding of temporal information, that is, the length of stimulus duration, during the retention interval. When variable lengths of samples were presented with a fixed retention interval, the monkeys made more incorrect responses when length differences between short and long samples were small in the DMS-D task, but not in the DMS-C task. This suggests that the codes of working memory retained in the DMS-D task were not absolute (analogical) but rather were relative (categorical) and related to differences in the duration of the samples.     

Ecstasy and agony: activation of the human amygdala in positive and negative emotion

Considerable evidence indicates that the amygdala plays a critical role in negative, aversive human emotions. Although researchers have speculated that the amygdala plays a role in positive emotion, little relevant evidence exists. We examined the neural correlates of positive and negative emotion using positron emission tomography (PET), focusing on the amygdala. Participants viewed positive and negative photographs, as well as interesting and uninteresting neutral photographs, during PET scanning. The left amygdala and ventromedial prefrontal cortex were activated during positive emotion, and bilateral amygdala activation occurred during negative emotion. High-interest, unusual photographs also elicited left-amygdala activation, a finding consistent with suggestions that the amygdala is involved in vigilance reactions to associatively ambiguous stimuli. The current results constitute the first neuroimaging evidence for a role of the amygdala in positive emotional reactions elicited by visual stimuli. Although the amygdala appears to play a more extensive role in negative emotion, it is involved in positive emotion as well.     

Conditioned behavioral and physiological changes associated with injections of a narcotic antagonist in morphine-dependent monkeys

Environmental stimuli which are repeatedly associated with the nalorphine-induced withdrawal syndrome in morphine-dependent monkeys acquire the ability to produce a variety of conditioned behavioral and physiological responses. Morphine-dependent rhesus monkeys were studied under a fixed-ratio schedule where every tenth lever press produced a food pellet. After several pairings of a stimulus (light or tone) with intravenous injection of a dose of nalorphine which produced an immediate and severe withdrawal syndrome, onset of the stimulus alone produced conditioned suppression of lever pressing, heartrate decrease, vomiting and salivation. Conditioned suppression of responding and conditioned heart-rate changes persisted in post-dependent monkeys for one to four months after termination of chronic morphine treatment. No conditioned electrocardiogram, respiration or temperature changes were ever seen. A second group of morphine-dependent rhesus monkeys was studied under a schedule where every lever press produced an intravenous injection of morphine. After 10 pairings of a light with the intravenous injection of a dose of nalorphine which produced marked withdrawal signs and increased responding for morphine, presentation of the light and injection of sahne produced conditioned increases in responding for morphine. A third group of morphine-dependent rhesus monkeys was studied under a schedule where every nth lever press (n = 1 to 10) terminated a stimulus light associated with periodic injections of nalorphine or naloxone; lever-press responding was engendered and subsequently maintained. Thus, stimuli associated with the nalorphineor naloxone-induced withdrawal syndrome can either suppress, enhance or maintain behavior depending on the schedule conditions.     

The bioelectrical activity of cerebellar structures in the freely-moving rat

Electrodes were implanted in the brains of 27 freelymoving rats and the bioelectrical activity of cerebellar cortical structures (lobus simplex, tuber verrais, lobus ansiformis, crus II) and the dentate nucleus was measured simultaneously with the activity of the cerebral cortex and dorsal hippocampus and respiratory rate and motor activity. Different behavioral states were produced by habituation procedures and by elaborating conditional avoidance reflexes to light-flash or click series. In addition, startle reflexes to acoustic stimuli were used to evaluate behavioral state. The following conclusions could be drawn: 1) in the awake rat the various cerebellar structures have clearly distinguishable bioelectrical activity patterns; 2) changes in these patterns depend on the actual behavioral state of the animal; 3) this dependence upon behavior is especially clear in crus II, one of the projection zones of the tactile and proprioceptive afferent nerves in the cerebellar cortex. The changes in the electrocerebellogram of the unrestrained rat may be used as an indicator of the behavioral state of the animal.