Expectation and temperament moderate amygdala and dorsal anterior cingulate cortex responses to fear faces

A chronic tendency to avoid novelty is often the result of a temperamental bias called inhibited temperament, and is associated with increased risk for anxiety disorders. Neuroimaging studies have demonstrated that an inhibited temperament is associated with increased amygdalar blood-oxygenation-level-dependent (BOLD) response to unfamiliar faces that were not expected; however, the effects of variations in expectancy remain unknown. Using functional magnetic resonance imaging (fMRI), we studied BOLD response to infrequently encountered fear faces that were either expected or not expected in 42 adults with an inhibited or an uninhibited temperament. Individuals with an inhibited temperament had greater amygdala, but less dorsal anterior cingulate cortex (dACC), BOLD response when the stimuli were expected. In contrast, those with an uninhibited temperament had a smaller amygdala but larger dorsal anterior cingulate cortex BOLD response when expecting to see fear faces. These findings demonstrate temperament differences in expectancy effects and provide preliminary evidence for the dACC as a neural substrate mediating differences in inhibited temperament. Enhanced amygdala sensitivity coupled with weak inhibitory control from the dACC may form a neural circuit mediating behaviors characteristic of inhibited temperament and risk for anxiety disorders.     

Elevated amygdala response to faces following early deprivation

A functional neuroimaging study examined the long-term neural correlates of early adverse rearing conditions in humans as they relate to socio-emotional development. Previously institutionalized (PI) children and a same-aged comparison group were scanned using functional magnetic resonance imaging (fMRI) while performing an Emotional Face Go/Nogo task. PI children showed heightened activity of the amygdala, a region that supports emotional learning and reactivity to emotional stimuli, and corresponding decreases in cortical regions that support perceptual and cognitive functions. Amygdala activity was associated with decreased eye-contact as measured by eye-tracking methods and during a live dyadic interaction. The association between early rearing environment and subsequent eye-contact was mediated by amygdala activity. These data support the hypothesis that early adversity alters human brain development in a way that can persist into childhood, and they offer insight into the socio-emotional disturbances in human behavior following early adversity.     

Multiple repetition priming of faces: Massed and spaced presentations

Previously viewing a face typically leads to a decrease in the amount of time taken to later identify it (“repetition priming”). Five repetition priming experiments are reported, which investigate whether multiple presentations of a face increase the amount of repetition priming. The results demonstrate similar amounts of priming from massed multiple presentations of the same face or a series of different images (freeze frames selected from a moving clip and presented in sequence), compared with a single unchanging presentation (Experiments 1 and 2). This is true even when different images are presented at prime and test (Experiment 3). However when multiple presentations were presented in a spaced fashion, with one or more intervening items between each repeat, there was significantly more priming in the multiple than single presentation condition (Experiment 4). This was true even when the face was named only once in both the multiple and single spaced conditions (Experiment 5). The results are discussed in relation to face motion.     

Infants' discrimination of photographs of faces following redundant presentations

Infants' discrimination of photographs of faces, as indicated by fixation toward novel targets, was the criterion used to evaluate familiarization conditions designed to facilitate the exercise of selective attention. Groups of 19- and 23-week-old infants were shown either pictures of different faces of the same sex, differing poses of the same face, or repeated exposures of the face that served as a test stimulus. The older infants demonstrated differential attention to novel over familiar stimuli during subsequent recognition tests, and an examination of their responsiveness during familiarization presentations indicated differing trends of looking activity.     

The amygdala is involved in affective priming effect for fearful faces

The object of this study was to investigate whether the amygdala is involved in affective priming effect after stimuli are encoded unconsciously and consciously. During the encoding phase, each masked face (fearful or neutral) was presented to participants six times for 17ms each, using a backward masking paradigm. During the retrieval phase, participants made a fearful/neutral judgment for each face. Half of the faces had the same valence as that seen during encoding (congruent condition) and the other half did not (incongruent condition). Participants were divided into unaware and aware groups based on their subjective and objective awareness assessments. The fMRI results showed that during encoding, the amygdala elicited stronger activation for fearful faces than neutral faces but differed in the hemisphere according to the awareness level. During retrieval, the amygdala showed a significant repetition priming effect, with the congruent faces producing less activation than the incongruent faces, especially for fearful faces. These data suggest that the amygdala is important in unconscious retrieving of memories for emotional faces whether they are encoded consciously or unconsciously.     

The accuracy and speed of repeated responses

Summary Although experimental psychologists measure the quality of performance in terms of either terminal accuracy or latency, no clear theoretical link has been recently made between these measurements. This paper reports two experiments which show that a fundamental limitation to performance, either in terms of speed or accuracy, is the delay since a previous movement was made. Under circumstances where eye-movements are controlled, the ensemble size appears not to affect response latency directly, but response-to-stimulus interval (RSI) has a highly significant effect. Furthermore, the accuracy of responses is independent of either ensemble size or entropy, but is again directly related to RSI. These results are discussed in terms of the instability and lability of the spatial information upon which the operator must act, and it is hypothesized that a major contributing factor to performance in serial tasks is the state of the subject's knowledge about the spaces he or she operates in.     

Brain responses differ to faces of mothers and fathers

We encounter many faces each day but relatively few are personally familiar. Once faces are familiar, they evoke semantic and social information known about the person. Neuroimaging studies demonstrate differential brain activity to familiar and non-familiar faces; however, brain responses related to personally familiar faces have been more rarely studied. We examined brain activity with fMRI in adults in response to faces of their mothers and fathers compared to faces of celebrities and strangers. Overall, faces of mothers elicited more activity in core and extended brain regions associated with face processing, compared to fathers, celebrity or stranger faces. Fathers’ faces elicited activity in the caudate, a deep brain structure associated with feelings of love. These new findings of differential brain responses elicited by faces of mothers and fathers are consistent with psychological research on attachment, evident even during adulthood.     

Effects of amount and kind of prior target-uncertainty reduction in the repeated presentations paradigm

Single letters were presented for varying numbers of repeated brief exposures. The S reported on the target after each presentation, identifying only those symbols perceived with certainty. A d’ analysis of the results revealed that target-uncertainty reduction produced significant facilitation in the average level of perceptual sensitivity only in a condition in which the target symbol was exposed prior to each trial. Prior knowledge of the target symbol without prior exposure produced a measurable, but nonsignificant, facilitation in sensitivity. The data suggested that the growth curve normally associated with the repeated-presentations paradigm may be the result of a progressive liberalization of the S’s criterion for reporting in some studies. The data further showed that prior exposure and perhaps prior knowledge can significantly alter the shape of the repetition curve when the target is a single letter. These findings were interpreted as an indication that both amount and kind of target-uncertainty reduction can produce significant changes in the repetition effect for single letters.     

Functional brain activation to emotional and nonemotional faces in healthy children: Evidence for developmentally undifferentiated amygdala function during the school-age period

The amygdala is a key region in emotion processing. In particular, fMRI studies have demonstrated that the amygdala is active during the viewing of emotional faces. Previous research has consistently found greater amygdala responses to fearful than to neutral faces in adults, convergent with a focus in the animal literature on the amygdala’s role in fear processing. Studies have shown that the amygdala also responds differentially to other facial emotion types in adults. Yet the literature regarding when this differential amygdala responsivity develops is limited and mixed. Thus, the goal of the present study was to examine amygdala responses to emotional and neutral faces in a relatively large sample of healthy school-age children (N?=?52). Although the amygdala was active in response to emotional and neutral faces, the results did not support the hypothesis that the amygdala responds differentially to emotional faces in 7- to 12-year-old children. Nonetheless, amygdala activity was correlated with the severity of subclinical depression symptoms and with emotional regulation skills. Additionally, sex differences were observed in frontal, temporal, and visual regions, as well as effects of pubertal development in visual regions. These findings suggest important differences in amygdala reactivity in childhood.     

Amygdala activation during masked presentation of emotional faces predicts conscious detection of threat-related faces

It has been argued that critical functions of the human amygdala are to modulate the moment-to-moment vigilance level and to enhance the processing and the consolidation of memories of emotionally arousing material. In this functional magnetic resonance study, pictures of human faces bearing fearful, angry, and happy expressions were presented to nine healthy volunteers using a backward masking procedure based on neutral facial expression. Activation of the left and right amygdala in response to the masked fearful faces (compared to neutral faces) was significantly correlated with the number of fearful faces detected. In addition, right but not left amygdala activation in response to the masked angry faces was significantly related to the number of angry faces detected. The present findings underscore the role of the amygdala in the detection and consolidation of memory for marginally perceptible threatening facial expression.     

Angry faces are tracked more easily than neutral faces during multiple identity tracking

We investigated whether and how emotional facial expressions affect sustained attention in face tracking. In a multiple-identity and object tracking paradigm, participants tracked multiple target faces that continuously moved around together with several distractor faces, and subsequently reported where each target face had moved to. The emotional expression (angry, happy, and neutral) of the target and distractor faces was manipulated. Tracking performance was better when the target faces were angry rather than neutral, whereas angry distractor faces did not affect tracking. The effect persisted when the angry faces were presented upside-down and when surface features of the faces were irrelevant to the ongoing task. There was only suggestive and weak evidence for a facilitatory effect of happy targets and a distraction effect of happy distractors in comparison to neutral faces. The results show that angry expressions on the target faces can facilitate sustained attention on the targets via increased vigilance, yet this effect likely depends on both emotional information and visual features of the angry faces.     

Temporal order: The effect of single versus repeated presentations,practice, and verbal feedback

Whereas Hirsh and Sherrick (1961) found that experienced Os could judge correctly the temporal order of a sound and a light presented repeatedly when the interval separating them was 20 msec, Hirsh and Fraisse (1964) found that naive Os required about 60 msec for the same accuracy of performance with single presentations of the same pair. This experiment examined the effects of single vs repeated presentations, practice, and verbal feedback on performance in the judgment of temporal order. The results indicate that performance under repeated presentation is significantly better than under single presentation, that learning effects are most pronounced during the first 4 of 16 sessions, and that the effects of feedback appear to depend on the precise wording given the S on how he is to perform.     

Comparison of emotional responses in monkeys with rhinal cortex or amygdala lesions

Four emotionally arousing stimuli were used to probe the behavior of monkeys with bilateral ablations of the entorhinal and perirhinal cortex. The monkeys' behavioral changes were then contrasted with those observed earlier (M. Meunier, J. Bachevalier, E. A. Murray, L. Málková, & M. Mishkin, 1999) in monkeys with either neurotoxic or aspiration lesions of the neighboring amygdala. Rhinal cortex ablations yielded several subtle behavioral changes but none of them resembled any of the disorders typically seen after amygdalectomies. The changes produced by rhinal damage took mainly the form of heightened defensiveness and attenuated submission and approach responses; that is, just the opposite of some of the most distinctive symptoms following amygdala damage. These findings raise the possibility that the rhinal cortex and amygdala have distinct, interactive functions in normal behavioral adaptation to affective stimuli.     

D-cycloserine potentiates the reconsolidation of cocaine-associated memories

Conditioned cue-induced relapse to drug seeking is a major challenge to the treatment of drug addiction. It has been proposed that D-cycloserine might be useful in the prevention of relapse by reducing the conditioned reinforcing properties of drug-associated stimuli through facilitation of extinction. Here we show that intrabasolateral amygdala infusions of D-cycloserine in fact potentiate the reconsolidation of stimulus–cocaine memories to increase cue-induced relapse to drug seeking in rats with an extensive drug self-administration history. This elevation of cocaine seeking was correlated with an increase in the expression of the reconsolidation-associated gene zif268.Drug addiction is often described as a chronic relapsing disorder, in which craving and relapse to drug seeking occur even after prolonged abstinence (Gawin and Kleber 1986; Lu et al. 2004). A major contributor to relapse is exposure to environmental stimuli that have previously been associated regularly with the effects of self-administered drugs of abuse. Such drug-associated stimuli induce craving in abstinent addicts, and precipitate relapse to drug seeking (Gawin and Kleber 1986; Ehrman et al. 1992; O''Brien et al. 1998; Childress et al. 1999). In experimental animals, a conditioned stimulus (CS) paired repeatedly with self-administered cocaine similarly induces relapse to drug seeking (de Wit and Stewart 1981; Fuchs et al. 1998; Grimm et al. 2001).The basolateral amygdala (BLA) is a primary locus of CS–US (unconditioned stimulus) associations (LeDoux 2000; Everitt et al. 2003), and is critical for the control of goal-directed behavior by conditioned reinforcers (Burns et al. 1993; Corbit and Balleine 2005). Furthermore, lesions of the BLA disrupt conditioned cue-induced reinstatement of drug seeking (Meil and See 1997) and the acquisition of drug seeking under a second-order schedule of reinforcement (Whitelaw et al. 1996). The infusion of antisense oligodeoxynucleotides targeting the immediate-early gene zif268 (also known as EGR1, Krox24, and NGFI-A) into the BLA impairs the reconsolidation of CS–cocaine associations and thereby reduces cue-induced cocaine seeking and relapse (Lee et al. 2005, 2006a). Memory reconsolidation is the process that is hypothesized to restabilize memories following their reactivation through stimulus re-exposure (Nader 2003), the disruption of which both results in amnesia and has been proposed to be a potential treatment strategy for neuropsychiatric disorders, such as post-traumatic stress and drug addiction in which persistent maladaptive memories play an important role (Lee et al. 2005; Brunet et al. 2007).An alternative therapeutic approach for such disorders is to use cognitive enhancement strategies to potentiate the extinction of the maladaptive memories (Ressler et al. 2004; Richardson et al. 2004). The partial N-methyl-D-aspartate (NMDA) receptor agonist D-cycloserine (DCS) potentiates extinction in aversive and appetitive tasks when administered both systemically and directly into the BLA (Walker et al. 2002; Ledgerwood et al. 2003; Botreau et al. 2006). However, under certain conditions intra-BLA DCS can increase, rather than reduce, subsequent fear memory expression (Lee et al. 2006b). This finding is consistent with a potentiation of fear memory reconsolidation, and predicts that DCS might also enhance drug memories, which would be a potentially major limitation in a therapeutic setting. Therefore, using conditions that have been previously demonstrated to engage drug memory reconsolidation in a translational model of cocaine seeking (Lee et al. 2006a); we investigated whether or not DCS infusion into the BLA would enhance memory reconsolidation to increase cocaine seeking. Also investigated was the expression of zif268 in the amygdala following DCS treatment and CS re-exposure since this plasticity gene provides a cellular correlate of memory reconsolidation (Lee et al. 2005).The subjects were 45 adult male Lister hooded rats, weighing 280–350 g. They were housed in pairs prior to surgery, and singly thereafter, in holding rooms maintained at 21°C on a reversed-light cycle (12 h light:12 h dark; lights on at 19:00). After recovery from surgery, food was restricted to 20 g/day. Water was freely available throughout the experiment. All procedures were conducted in accordance with the UK 1986 Animals (Scientific Procedures) Act (Project License PPL 80/1767). Rats were implanted with a single catheter in the right jugular vein, and also with bilateral chronic indwelling guide cannulae targeting the BLA. The coordinates for cannulae implantation were (relative to bregma): AP − 2.6; ML ± 4.5; DV − 5.6 (from dura). Details of the intravenous and stereotaxic surgical procedures are described elsewhere (Di Ciano and Everitt 2001). A minimum of 7 d was allowed before behavioral training and testing began.All behavioral procedures were carried out in operant chambers (Med Associates) as previously described (Di Ciano and Everitt 2001), and were based on previous experiments (Lee et al. 2006a). Rats underwent 10 d of cocaine self-administration training under a fixed-ratio-1 (FR1) schedule of reinforcement. At the start of each self-administration session, two levers were inserted into the operant chamber and the house light was illuminated. Each response on the active lever (counterbalanced left or right) was reinforced with a single infusion of i.v. cocaine (0.25 mg in 0.1 mL over 5 s per infusion), accompanied by a 20-s illumination of the CS light located above the active lever, during which both levers were retracted and the house light was extinguished. Responses on the other, inactive, lever had no programmed consequence. To prevent accidental overdose, rats were limited to 30 infusions per hour in the 3-h sessions. In the event of 30 infusions being received, the levers were retracted and the house light extinguished until an hour had elapsed, after which the levers were again extended and the house light illuminated.The memory for the CS–cocaine association was reactivated in a single 30-min session through 30 noncontingent presentations of the CS light (20 s; 40-s ISI). No levers were present during the reactivation session, which took place 3 d after the completion of self-administration training, and 20 min following infusion of DCS (Sigma, UK; 20 μg/μL; 0.5 μL/side; 0.25 μL/min) or phosphate buffered saline (PBS) into the BLA as described previously (Lee et al. 2006b). The absence of the levers should decrease the probability of substantial reactivation of the instrumental memory. Nonreactivated groups were infused with DCS and then returned immediately to the home cage without a behavioral test session.Testing, which took place 6 d after self-administration training, involved the levers again being extended into the operant chamber and assessed the impact of the CS upon instrumental responding after 6-d abstinence as a model of cue-induced relapse. A response on the active lever was reinforced by a 1-s presentation of the CS light, during which the house light was extinguished, and a response on the inactive lever again had no programmed consequence. There were no cocaine infusions, and the number of lever presses was recorded in a 60-min session. The rats were subsequently retested on the following day.After completion of behavioral testing, the rats were perfused and their brains cut to produce 60 μm coronal sections, which were stained with cresyl violet. Assessment was conducted under light microscopy, and subjects were only included in the statistical analysis if the injectors were located bilaterally within the BLA, and there was no bilateral damage to the amygdala or any other area of the brain (5 rats were excluded on this basis). Fourteen rats were killed by carbon dioxide inhalation 2 h after memory reactivation (or at the same time point following infusions and nonreactivation). Their brains were extracted, the BLA microdissected bilaterally, and the samples frozen on dry ice and stored at –80°C prior to the quantification of zif268 protein levels through Western blot analysis as described previously (Lee et al. 2005).All rats included in the behavioral analyses had cannulae placed bilaterally in the BLA (Fig. 1). There was no difference between any of the groups during cocaine self-administration training and on average rats received 505 pairings of the light CS with an infusion of cocaine (data not shown; Condition × DCS: F < 1).Open in a separate windowFigure 1.Location of injectors within the BLA. Schematic representation of the brain at three rostro-caudal levels (−2.30, −2.56, and −2.80 mm from bregma). All rats included in the statistical analyses had injectors placed bilaterally in the BLA (× = PBS reactivated; • = DCS reactivated; □ = PBS nonreactivated; △ = DCS nonreactivated).Infusion of DCS into the BLA before drug cue re-exposure elevated subsequent active lever responding in a reactivation-dependent manner (Fig. 2). For the first test, ANOVA revealed a significant DCS × Reactivation × Lever interaction (F _(1,22) = 8.62; P < 0.01), as well as a significant DCS × Reactivation interaction (F _(1,22) = 4.71; P < 0.05). The effect was specific to the reactivated condition, as DCS infusion had no impact upon the nonreactivated condition (Fs < 1). This was confirmed by a significant DCS × Lever interaction (F _(1,13) = 13.12; P < 0.01) for the reactivated condition, and a significant main effect of DCS (F _(1,13) = 9.66; P < 0.01), but no effect of DCS on inactive lever presses (F < 1). The DCS-induced elevation of responding was again observed 24 h later in test 2 (DCS × Reactivation × Lever: F _(1,22) = 4.44; P < 0.05), indicating a persistent potentiation of responding, and an overall analysis revealed no difference in the effect of DCS between tests 1 and 2 (DCS × Reactivation × Lever: F _(1,13) = 7.41; P < 0.02; DCS × Reactivation × Lever × Test: F _(1,22) = 1.66; P > 0.21).Open in a separate windowFigure 2.Effect of prereactivation intra-BLA DCS on cocaine seeking. The number of active and inactive lever presses during the 60-min tests are presented for rats infused 3 d and tested 6 d after the end of self-administration training (A) in both the reactivated (PBS n = 8, DCS n = 7) and nonreactivated (PBS n = 6, DCS n = 5) conditions. DCS increased subsequent active lever responding across both bins in a reactivation-dependent manner, and the elevation was observed in a further test 24 h later (B). Data presented as mean + SEM. An asterisk (*) represents a significant DCS × Lever interaction, P < 0.05.Infusion of DCS into the BLA before drug cue re-exposure potentiated the subsequent expression in the BLA of zif268 protein levels 2 h after the reactivation session as measured by Western blotting analysis (Fig. 3). ANOVA revealed a significant effect of DCS when infused prior to memory reactivation (F _(1,6) = 9.42; P < 0.03). However, there was no effect of DCS treatment when infused in the absence of memory reactivation (F _(1,4) = 1.41; P > 0.30).Open in a separate windowFigure 3.Effect of prereactivation intra-BLA DCS on zif268 protein levels in the BLA. The images of the gels were quantified and normalized to give a measure of zif268 protein relative to control PBS-infused rats. DCS increased the levels of zif268 protein 2 h after memory reactivation [(A); n = 4 per group], but not at the equivalent time point in the nonreactivated condition [(B); n = 3 per group]. Data presented as mean + SEM.The present results demonstrate that infusion of the partial NMDA receptor agonist DCS into the BLA shortly before re-exposure to a cocaine-associated CS increased subsequent cocaine seeking behavior maintained by that CS. Moreover, the expression of the reconsolidation-associated gene zif268 in the amygdala was also elevated by DCS infusion coupled with CS re-exposure. Both of these effects were critically dependent upon rats being re-exposed to the cocaine CS shortly after DCS infusion. We have previously demonstrated both that paired presentations of CS and reward are necessary for the acquisition of conditioned reinforcing properties (Parkinson et al. 2005), and that re-exposure to contextual and other stimuli are insufficient to reactivate the CS–cocaine memory (Lee et al. 2006a). Therefore, the present results most likely reflect an effect of DCS to potentiate the reconsolidation of the CS–cocaine memory, thereby enhancing the appetitive properties of the CS and increasing cue-induced cocaine seeking.DCS has been shown to potentiate a number of memory plasticity processes, including initial memory acquisition/consolidation (Monahan et al. 1989; Land and Riccio 1999; Kalisch et al. 2008), memory extinction (Walker et al. 2002; Ledgerwood et al. 2003), and memory reconsolidation (Lee et al. 2006b). Moreover, the effect of DCS here was memory reactivation dependent and hence not a result of an acute effect upon behavior. Therefore, the elevation of subsequent cue-induced cocaine seeking reflects an enhancement of CS–cocaine memory expression. The delay of 3 d between the end of self-administration training and DCS infusion ensured that initial consolidation processes were complete, and hence the effect of DCS is more likely be related to memory extinction or reconsolidation, of which only a potentiation of memory reconsolidation can account for the present results. Therefore, the behavioral evidence strongly indicates that DCS infusion into the BLA can potentiate drug memory reconsolidation to elevate subsequent drug seeking, at least under certain circumstances.The cellular data obtained in the present study provides further evidence that DCS elevation of NMDA receptor-mediated glutamate transmission enhances cocaine seeking through the potentiation of drug memory reconsolidation. The expression of the immediate-early gene zif268 has been shown in several settings to be a critical and causal mechanism in memory reconsolidation. The expression of zif268 at both the mRNA and protein levels is upregulated by stimulus re-exposure that induces the reconsolidation of aversive contextual fear (Hall et al. 2001; Lee et al. 2004), discrete cue fear (Hall et al. 2001), and conditioned withdrawal memories (Hellemans et al. 2006), as well as appetitive CS–cocaine associations (Thomas et al. 2003). Moreover, functional reduction of zif268 expression in transgenic mice or through the local intracerebral infusion of zif268 antisense oligodeoxynucleotides impairs the reconsolidation of several types of memory (Bozon et al. 2003; Lee et al. 2004, 2005, 2006a; Hellemans et al. 2006). Of special importance is the observation that zif268 expression in the BLA is correlated with, and necessary for, the reconsolidation of CS–cocaine memories (Thomas et al. 2003; Lee et al. 2005, 2006a), and hence zif268 protein levels in the BLA are a cellular marker for drug memory reconsolidation. Here zif268 protein levels in the BLA were greatly increased by intra-BLA DCS infusion in conjunction with memory reactivation, strongly suggesting that DCS acts to enhance the cellular mechanisms of drug memory reconsolidation, resulting in the observed elevation of drug seeking behavior at a later test. Importantly, this potentiation of zif268 expression was not observed when DCS was infused in the absence of a memory reactivation session, thus demonstrating that the impact of DCS conforms to the reactivation-dependent criterion of memory reconsolidation effects (Lewis 1979; Dudai 2004).Previous studies have demonstrated that treatment with DCS in conjunction with nonreinforced CS re-exposure results in a subsequent decrease in drug-related behavior, consistent with an enhancement of drug memory extinction, leading to the suggestion that DCS might be used in conjunction with cue exposure therapy as a treatment strategy for addiction (Botreau et al. 2006; Kelley et al. 2007). However, these studies used a drug conditioned place preference procedure, involving only four experimenter-administered intraperitoneal injections of cocaine. The present study uses a more translationally relevant model of chronic cocaine self-administration with hundreds of pairings of the CS with intravenous cocaine. Therefore, the effect of DCS to increase subsequent cue-induced cocaine seeking may reflect more accurately the likely outcome of a DCS-based treatment strategy, given the chronic nature of drug exposure characteristic of addiction. Moreover, it may be the case that DCS combined with cue exposure may not be effective in prolonging abstinence and preventing relapse, as this approach may, in fact, further strengthen the detrimental impact of exposure to drug-associated stimuli, making relapse more likely.The different levels of drug memory strength between the conditioned place preference and self-administration studies can explain the contrasting outcomes observed with DCS. The strength of conditioning is an important factor in determining whether memory-modulating treatments impact upon reconsolidation or extinction, with stronger training biasing toward memory reconsolidation (Eisenberg et al. 2003). Therefore, it is not surprising that DCS enhanced drug memory reconsolidation here, while potentiating extinction in the more weakly conditioned place preference studies, especially given that we have previously shown DCS to have bidirectional mnemonic effects in a fear conditioning procedure (Lee et al. 2006b). Future studies will be required to clarify parametrically the impact of memory strength and also the extent of cue exposure upon the effects of DCS. In addition, while the present study focused upon the Pavlovian conditioned reinforcing effects of drug-associated stimuli, due to their importance in relapse, the effect of DCS upon instrumental responding is also of interest. Any impact of DCS upon instrumental memories is likely to be mediated by neural loci beyond the amygdala, and so it will be important to establish how systemic, rather than localized intracerebral, injections of DCS affect the many drug-related memories that contribute to drug seeking behavior. The present results do not invalidate the potential application of DCS in the future treatment of drug addiction. However, they demonstrate clearly that its use must be carefully controlled, as there is the distinct likelihood that memory reconsolidation, rather than extinction, processes will be potentiated, leading to the deleterious consequence of promoting the conditioned elicitation of drug seeking behavior and relapse.     

Event-related brain potential in responses to social messages via human faces

In two experiments participants were presented a sequence of facial photographs to examine effects of pleasantness of facial expressions, namely, pleasant and unpleasant, and task relevance on P300 component of event-related brain potentials in the 3-stimulus version of the oddball task. Exp. 1 showed that, although the amplitudes of P300 were the largest in response to task-relevant target stimuli and moderate in response to task-irrelevant nontargets, the Pleasantness of stimuli did not affect the amplitudes of P300 when the stimuli were task-relevant or irrelevant. Data in Exp. 2 suggested that the emotional significance rather than physical characteristics of stimuli might be responsible for generation of P300 by task-irrelevant nontargets.     

Links between rapid ERP responses to fearful faces and conscious awareness

To study links between rapid ERP responses to fearful faces and conscious awareness, a backward‐masking paradigm was employed where fearful or neutral target faces were presented for different durations and were followed by a neutral face mask. Participants had to report target face expression on each trial. When masked faces were clearly visible (200 ms duration), an early frontal positivity, a later more broadly distributed positivity, and a temporo‐occipital negativity were elicited by fearful relative to neutral faces, confirming findings from previous studies with unmasked faces. These emotion‐specific effects were also triggered when masked faces were presented for only 17 ms, but only on trials where fearful faces were successfully detected. When masked faces were shown for 50 ms, a smaller but reliable frontal positivity was also elicited by undetected fearful faces. These results demonstrate that early ERP responses to fearful faces are linked to observers' subjective conscious awareness of such faces, as reflected by their perceptual reports. They suggest that frontal brain regions involved in the construction of conscious representations of facial expression are activated at very short latencies.