Left Amygdala Activation Research Articles

Negative Urgency Mediates the Relationship between Amygdala and Orbitofrontal Cortex Activation to Negative Emotional Stimuli and General Risk-Taking.

The tendency toward impulsive behavior under emotional duress (negative and positive urgency) predicts a wide range of maladaptive risk-taking and behavioral disorders. However, it remains unclear how urgency relates to limbic system activity as induced from emotional provocation. This study used functional magnetic resonance imaging to examine the relationship between brain responses to visual emotional stimuli and urgency traits. Twenty-seven social drinkers (mean age = 25.2, 14 males) viewed negative (Neg), neutral (Neu), and positive (Pos) images during 6 fMRI scans. Brain activation was extracted from a priori limbic regions previously identified in studies of emotional provocation. The right posterior orbitofrontal cortex (OFC) and left amygdala were activated in the [Neg>Neu] contrast, whereas the left posterior OFC was activated in the [Pos>Neu] contrast. Negative urgency was related to the right lateral OFC (r = 0.43, P = 0.03) and the left amygdala (r = 0.39, P = 0.04) [Neg>Neu] activation. Negative urgency also mediated the relationship between [Neg>Neu] activation and general risk-taking (regression weights = 3.42 for right OFC and 2.75 for the left amygdala). Emotional cue-induced activation in right lateral OFC and left amygdala might relate to emotion-based risk-taking through negative urgency.

Amygdala Activation and Emotional Processing in Adolescents at Risk for Substance Use Disorders

Studies are needed that examine neurobiological characteristics in high-risk individuals prior to substance use disorder (SUD) development. In this pilot study, 4 adolescent subjects at high risk for SUD (having at least 1 parent with an SUD) were compared with 4 adolescent reference subjects on a cortico-limbic reactivity paradigm, where they were presented with affect-laden faces or geometric shapes. Functional magnetic resonance imaging was used to measure cortical activation in response to these stimuli. High-risk subjects, compared to low-risk, exhibited greater left amygdala activation (t = 2.76, df = 6, p = 0.03), suggesting they may exhibit hyperresponsivity of the amygdala in response to emotional stimuli.

Effects of Nicotine Deprivation and Replacement on BOLD-fMRI Response to Smoking Cues as a Function of DRD4 VNTR Genotype

Reactivity to smoking cues is an important factor in the motivation to smoke and has been associated with the dopamine receptor 4 variable number tandem repeat (DRD4 exon III VNTR) polymorphism. However, little is known about the associated neural mechanisms. Non-treatment-seeking Caucasian smokers completed overnight abstinence and viewed smoking and neutral cues during 2 separate functional magnetic resonance imaging scans while wearing either a nicotine or placebo patch (order randomized) and were genotyped for the DRD4 VNTR. We conducted mixed-effects repeated-measures analyses of variance (within-subject factor: nicotine or placebo patch; between-subject factor: DRD4 long [L: ≥ 1 copy of ≥ 7 repeats] or short [S: 2 copies ≤ 6 repeats] genotype) of 6 a priori regions of interest. Relative to neutral cues, smoking cues elicited greater activity in bilateral ventral striatum and left amygdala during nicotine replacement and deactivation in these regions during nicotine deprivation. A patch × DRD4 interaction was observed in the left amygdala, an area associated with appetitive reinforcement and relapse risk, such that S allele carriers demonstrated greater activation on active patch than on placebo patch. Brain systems associated with reward salience may become primed and overreactive at nicotine replacement doses intended for the first step of smoking cessation and may become inhibited during nicotine withdrawal in DRD4 S but not in DRD4 L carriers. These findings are consistent with the role of these regions in drug reinforcement and suggest a differential influence of nicotine replacement on amygdala activation in the association of incentive salience with smoking stimuli across DRD4 genotypes.

Preliminary Functional MRI Neural Correlates of Executive Functioning and Empathy in Children with Obstructive Sleep Apnea

Pediatric obstructive sleep apnea (OSA) is associated with neurocognitive deficits. However, the neural substrates underlying such deficits remain unknown. To examine executive control and emotional processing in OSA, 10 children age 7 to 11 y with polysomnographically diagnosed OSA and 7 age- and sex-matched controls underwent a color-word Stroop task and an empathy task consisting of dynamic visual scenarios depicting interpersonal harm or neutral actions in a magnetic resonance imaging (MRI) scanner. Functional MRI data were processed using MATLAB 7.12 with SPM8 for region of interest (ROI) analyses, and a general linear model was used with regressors for each trial type in each task. For the Stroop task, accuracy was similar in the two groups, with no differences in the effect of incongruency on success rates. OSA showed greater neural activity than controls in eight ROI clusters for incongruent versus congruent trials (P < 0.001). Within the a priori ROIs, the anterior cingulate cortex was significantly different between groups (P < 0.05). For perceiving harm versus neutral actions, ROI analysis revealed a significant correlation between apnea-hypopnea index and left amygdala activity in harm versus neutral actions (r = -0.71, P < 0.05). These results provide the first functional MRI evidence that cognitive and empathetic processing is influenced by obstructive sleep apnea (OSA) in children. Children with OSA show greater neural recruitment of regions implicated in cognitive control, conflict monitoring, and attentional allocation in order to perform at the same level as children without OSA. When viewing empathy-eliciting scenarios, the severity of OSA predicted less sensitivity to harm in the left amygdala.

The route to an integrative associative memory is influenced by emotion.

Though the hippocampus typically has been implicated in processes related to associative binding, special types of associations – such as those created by integrative mental imagery – may be supported by processes implemented in other medial temporal-lobe or sensory processing regions. Here, we investigated what neural mechanisms underlie the formation and subsequent retrieval of integrated mental images, and whether those mechanisms differ based on the emotionality of the integration (i.e., whether it contains an emotional item or not). Participants viewed pairs of words while undergoing a functional MRI scan. They were instructed to imagine the two items separately from one another (“non-integrative” study) or as a single, integrated mental image (“integrative” study). They provided ratings of how successful they were at generating vivid images that fit the instructions. They were then given a surprise associative recognition test, also while undergoing an fMRI scan. The cuneus showed parametric correspondence to increasing imagery success selectively during encoding and retrieval of emotional integrations, while the parahippocampal gyri and prefrontal cortices showed parametric correspondence during the encoding and retrieval of non-emotional integrations. Connectivity analysis revealed that selectively during negative integration, left amygdala activity was negatively correlated with frontal and hippocampal activity. These data indicate that individuals utilize two different neural routes for forming and retrieving integrations depending on their emotional content, and they suggest a potentially disruptive role for the amygdala on frontal and medial-temporal regions during negative integration.

Occupancy of serotonin transporters in the amygdala by paroxetine in association with attenuation of left amygdala activation by negative faces in major depressive disorder

Amygdala hyperactivation in major depressive disorder (MDD) might be attenuated by selective serotonin reuptake inhibitors (SSRIs), but the working mechanism remains unclear. We hypothesized that higher amygdala serotonin transporter (SERT) occupancy by paroxetine results in greater attenuation of amygdala activation by negative facial expressions in MDD patients. We treated fifteen MDD patients (22–55 years) with paroxetine 20–50mg/day. After 6 and 12 weeks, we quantified (1) clinical response (≥50% decrease in Hamilton Depression Rating Scale (HDRS), (2) SERT occupancy in both amygdala measured by repeated [123I]β-CIT single photon emission computed tomography (SPECT), and (3) amygdala activation when viewing fearful and angry (negative) faces with repeated functional MRI scans. Response rates were 4/15 and 9/15 at 6 and 12 weeks, respectively. Attenuation of left amygdala activation was associated with amygdala SERT occupancy (P=0.006) and response (P=0.015). This association may provide a rationale for decreased limbic activity seen during treatment of MDD. It might also explain the rapid decrease in negative attentional bias and amygdala activation caused by SSRIs.

Acute Effects of Heroin on Negative Emotional Processing: Relation of Amygdala Activity and Stress-Related Responses

Negative emotional states and abnormal stress reactivity are central components in drug addiction. The brain stress system in the amygdala is thought to play a key role in the maintenance of drug dependence through negative reinforcement. Although acute heroin administration was found to reduce anxiety, craving, and stress hormone release, whether these effects are reflected in amygdala activity has not yet been investigated. With a randomized, crossover, double-blind design, saline and heroin were administered to 22 heroin-dependent patients, whereas 17 healthy control subjects were included for the placebo administration only. We used functional magnetic resonance imaging to investigate blood oxygen level-dependent responses during fearful faces processing. Stress reactivity was measured by adrenocorticotropic hormone levels and by cortisol concentrations in serum and saliva 60 min after substance administration. Anxiety and craving levels were assessed with self-report ratings. Heroin administration acutely reduced the left amygdala response to fearful faces relative to the saline injection. Patients receiving saline showed a significantly higher left amygdala response to fearful faces than healthy control subjects, whose activity did not differ from patients receiving heroin. The left amygdala activity correlated significantly with scores on state-anxiety and levels of adrenocorticotropic hormone, serum cortisol, and saliva cortisol among all patients and control subjects. Our results show a direct relation between the acute heroin effects on stress-related emotions, stress reactivity, and left amygdala response to negative facial expressions. These findings provide new insights into the mechanisms underlying negative reinforcement in heroin addiction and the effects of regular heroin substitution.

Emotional modulation of motor response inhibition in women with borderline personality disorder: an fMRI study

Both emotion regulation and impulsivity are core aspects of borderline personality disorder (BPD) pathology. Although both problems may be combined specifically in BPD, few studies to date have investigated the emotional modulation of impulsivity in BPD. Women with BPD and matched healthy controls performed go/no-go tasks after induction of anger, joy or a neutral mood by vocally presented short stories. Dependent variables were the behavioural results and functional magnetic resonance imaging data. We included 17 women with BPD and 18 controls in our study. No behavioural group differences were found. However, patients with BPD showed stronger activation of the left amygdala and weaker activation of the subgenual anterior cingulate during anger induction than controls. Inhibition in the go/no-go task after anger induction increased activity in the left inferior frontal cortex in controls, but not in women with BPD, who, in turn, showed increased activation in the subthalamic nucleus. Findings cannot be generalized to men, and 4 patients were taking antidepressant medication (selective serotonin reuptake inhibitors). In addition, no patient control group was investigated, thus we do not know whether findings are specific to BPD compared with other disorders. Our findings are consistent with the view that a disturbed amygdala-prefrontal network in patients with BPD is compensated by a subcortical loop involving the subthalamic nucleus, leading to normal behavioural inhibition in these patients.

Detecting emotion in others: increased insula and decreased medial prefrontal cortex activation during emotion processing in elite adventure racers

Understanding the neural processes that characterize elite performers is a first step to develop a neuroscience model that can be used to improve performance in stressful circumstances. Adventure racers are elite athletes that operate in small teams in the context of environmental and physical extremes. In particular, awareness of team member's emotional status is critical to the team's ability to navigate high-magnitude stressors. Thus, this functional magnetic resonance imaging (fMRI) study examined the hypothesis that adventure racers would show altered emotion processing in brain areas that are important for resilience and social awareness. Elite adventure racers (n = 10) were compared with healthy volunteers (n = 12) while performing a simple emotion face-processing (modified Hariri) task during fMRI. Across three types of emotional faces, adventure racers showed greater activation in right insula, left amygdala and dorsal anterior cingulate. Additionally, compared with healthy controls adventure racers showed attenuated right medial prefrontal cortex activation. These results are consistent with previous studies showing elite performers differentially activate neural substrates underlying interoception. Thus, adventure racers differentially deploy brain resources in an effort to recognize and process the internal sensations associated with emotions in others, which could be advantageous for team-based performance under stress.

Parametric Modulation of Neural Activity by Emotion in Youth With Bipolar Disorder, Youth With Severe Mood Dysregulation, and Healthy Volunteers

CONTEXT Youth with bipolar disorder (BD) and those with severe, nonepisodic irritability (severe mood dysregulation [SMD]) exhibit amygdala dysfunction during facial emotion processing. However, studies have not compared such patients with each other and with comparison individuals in neural responsiveness to subtle changes in facial emotion; the ability to process such changes is important for social cognition. To evaluate this, we used a novel, parametrically designed faces paradigm. OBJECTIVE To compare activation in the amygdala and across the brain in BD patients, SMD patients, and healthy volunteers (HVs). DESIGN Case-control study. SETTING Government research institute. PARTICIPANTS Fifty-seven youths (19 BD, 15 SMD, and 23 HVs). MAIN OUTCOME MEASURE Blood oxygenation level-dependent data. Neutral faces were morphed with angry and happy faces in 25% intervals; static facial stimuli appeared for 3000 milliseconds. Participants performed hostility or nonemotional facial feature (ie, nose width) ratings. The slope of blood oxygenation level-dependent activity was calculated across neutral-to-angry and neutral-to-happy facial stimuli. RESULTS In HVs, but not BD or SMD participants, there was a positive association between left amygdala activity and anger on the face. In the neutral-to-happy whole-brain analysis, BD and SMD participants modulated parietal, temporal, and medial-frontal areas differently from each other and from that in HVs; with increasing facial happiness, SMD patients demonstrated increased, and BD patients decreased, activity in the parietal, temporal, and frontal regions. CONCLUSIONS Youth with BD or SMD differ from HVs in modulation of amygdala activity in response to small changes in facial anger displays. In contrast, individuals with BD or SMD show distinct perturbations in regions mediating attention and face processing in association with changes in the emotional intensity of facial happiness displays. These findings demonstrate similarities and differences in the neural correlates of facial emotion processing in BD and SMD, suggesting that these distinct clinical presentations may reflect differing dysfunctions along a mood disorders spectrum.

Unseen fearful faces promote amygdala guidance of attention

Little is known about the network of brain regions activated prior to explicit awareness of emotionally salient social stimuli. We investigated this in a functional magnetic resonance imaging study using a technique that combined elements of binocular rivalry and motion flash suppression in order to prevent awareness of fearful faces and houses. We found increased left amygdala and fusiform gyrus activation for fearful faces compared to houses, despite suppression from awareness. Psychophysiological interaction analyses showed that amygdala activation was associated with task-specific (fearful faces greater than houses) modulation of an attention network, including bilateral pulvinar, bilateral insula, left frontal eye fields, left intraparietal sulcus and early visual cortex. Furthermore, we report an unexpected main effect of increased left parietal cortex activation associated with suppressed fearful faces compared to suppressed houses. This parietal finding is the first report of increased dorsal stream activation for a social object despite suppression, which suggests that information can reach parietal cortex for a class of emotionally salient social objects, even in the absence of awareness.

Stress sensitive healthy females show less left amygdala activation in response to withdrawal-related visual stimuli under passive viewing conditions

The amygdalae are key players in the processing of a variety of emotional stimuli. Especially aversive visual stimuli have been reported to attract attention and activate the amygdalae. However, as it has been argued that passively viewing withdrawal-related images could attenuate instead of activate amygdalae neuronal responses, its role under passive viewing conditions remains unclear. Furthermore, because individual sensitivity to stress reactions has been shown to modulate amygdalae processing, the aim of the current event-related fMRI study was to investigate whether individual differences in stress proneness could influence amygdala responses while passively viewing withdrawal and approach-related visual images. We presented 14 healthy female subjects with a random sequence of images of happy ‘healthy’ baby faces (approach-related) and baby faces disfigured by severe dermatological conditions (withdrawal-related). No instructions were given other than to watch the images attentively. We integrated individual perceived stress (PSS) scores in our analysis. The processing of withdrawal-related pictures resulted in less left amygdala activity in females scoring higher on perceived stress. Our findings suggest that stress-sensitive healthy females are less able to fully attend to withdrawal-related visual material and in essence avoid exposure to such images in an effort to reduce strong psychophysiological responses. Although the relatively small number of participants limits drawing firm conclusions, we suggest that in passive viewing emotional brain imaging paradigms, individual information on stress proneness should be included in the interpretation of amygdala neuronal processes.

The effect of the serotonin transporter polymorphism (5-HTTLPR) on amygdala function: a meta-analysis.

The 5-HTTLPR polymorphism has been widely regarded as a potential genetic risk factor for affective disorders. Consistent with this, this polymorphism has been associated with altered amygdala responses at rest and in response to aversive stimuli. However, the strength of this association remains uncertain. We sought to synthesize existing data on the association between the 5-HTTLPR polymorphism and amygdala activation and ascertain the strength of evidence for this association. Meta-analytic techniques were applied to data from relevant published studies and unpublished data sets to obtain an estimate of the likely magnitude of effect of any association. The large number of studies allowed us to apply a formal test of publication bias, as well as explore the impact of various study-level characteristics on the magnitude of the observed effect size. Our meta-analysis indicated that there is a statistically significant but small effect of 5-HTTLPR on left and right amygdala activity. However, there was considerable between-study heterogeneity, which could not be fully accounted for by the study design and sample characteristics that we investigated. In addition, there was evidence of excess statistical significance among published studies. These findings indicate that the association between the 5-HTTLPR and amygdala activation is smaller than originally thought, and that the majority of previous studies have been considerably under powered to reliably demonstrate an effect of this size.

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.

Sex differences in brain activation to emotional stimuli: A meta-analysis of neuroimaging studies

Substantial sex differences in emotional responses and perception have been reported in previous psychological and psychophysiological studies. For example, women have been found to respond more strongly to negative emotional stimuli, a sex difference that has been linked to an increased risk of depression and anxiety disorders. The extent to which such sex differences are reflected in corresponding differences in regional brain activation remains a largely unresolved issue, however, in part because relatively few neuroimaging studies have addressed this issue. Here, by conducting a quantitative meta-analysis of neuroimaging studies, we were able to substantially increase statistical power to detect sex differences relative to prior studies, by combining emotion studies which explicitly examined sex differences with the much larger number of studies that examined only women or men. We used an activation likelihood estimation approach to characterize sex differences in the likelihood of regional brain activation elicited by emotional stimuli relative to non-emotional stimuli. We examined sex differences separately for negative and positive emotions, in addition to examining all emotions combined. Sex differences varied markedly between negative and positive emotion studies. The majority of sex differences favoring women were observed for negative emotion, whereas the majority of the sex differences favoring men were observed for positive emotion. This valence-specificity was particularly evident for the amygdala. For negative emotion, women exhibited greater activation than men in the left amygdala, as well as in other regions including the left thalamus, hypothalamus, mammillary bodies, left caudate, and medial prefrontal cortex. In contrast, for positive emotion, men exhibited greater activation than women in the left amygdala, as well as greater activation in other regions including the bilateral inferior frontal gyrus and right fusiform gyrus. These meta-analysis findings indicate that the amygdala, a key region for emotion processing, exhibits valence-dependent sex differences in activation to emotional stimuli. The greater left amygdala response to negative emotion for women accords with previous reports that women respond more strongly to negative emotional stimuli, as well as with hypothesized links between increased neurobiological reactivity to negative emotion and increased prevalence of depression and anxiety disorders in women. The finding of greater left amygdala activation for positive emotional stimuli in men suggests that greater amygdala responses reported previously for men for specific types of positive stimuli may also extend to positive stimuli more generally. In summary, this study extends efforts to characterize sex differences in brain activation during emotion processing by providing the largest and most comprehensive quantitative meta-analysis to date, and for the first time examining sex differences as a function of positive vs. negative emotional valence. The current findings highlight the importance of considering sex as a potential factor modulating emotional processing and its underlying neural mechanisms, and more broadly, the need to consider individual differences in understanding the neurobiology of emotion.

Neural correlates of automatic perceptual sensitivity to facial affect in posttraumatic stress disorder subjects who survived L’Aquila eartquake of April 6, 2009

The "Emotional Numbing" (EN) constitutes one of the core symptoms in PTSD although its exact nature remains elusive. This disorder shows an abnormal response of cortical and limbic regions which are normally involved in understanding emotions since the very earliest stages of the development of processing ability. The aim of our study, which included ten physically healthy subjects with PTSD, diagnosed according to DSM-IV-TR, who survived L'Aquila earthquake of April 6, 2009, and 10 healthy controls matching for age, sex and education, was to examine automatic perceptual sensitivity to facial affect in PTSD, through an affective priming task that was administered during functional magnetic resonance (fMRI). Behavioural data revealed in the PTSD group a higher sensitivity to negative facial affect on an automatic processing level. FMRI data analysis revealed that PTSD subjects showed a significantly higher activation in right insula and left amygdala that we did not observe in healthy subjects; on the contrary, healthy controls showed a greater activation of left lingual gyrus. Our data support the hypothesis that PTSD appears to be sensitive to negative affect on an automatic processing level and correlates with the activation of specific areas involved in processing emotions. An elevated activation of these areas may underlie the emotion dysregulation in PTSD and could explain the Emotional Numbing symptom associated with this disorder. The present study suffers of a number of limitations, for instance, the relatively small sample size did not allow the application of alternative statistical models.

Yohimbine-Induced Amygdala Activation in Pathological Gamblers: A Pilot Study

Rationale and ObjectivesThere is evidence that drug addiction is associated with increased physiological and psychological responses to stress. In this pilot functional magnetic resonance imaging (fMRI) study we assessed whether a prototype behavioral addiction, pathological gambling (PG), is likewise associated with an enhanced response to stress.MethodsWe induced stress by injecting yohimbine (0.2–0.3 mg/kg, IV), an alpha-2 adrenoceptor antagonist that elicits stress-like physiological and psychological effects in humans and in laboratory animals, to four subjects with PG and to five non-gamblers mentally healthy control subjects. Their fMRI brain responses were assessed along with subjective stress and gambling urges ratings.ResultsVoxelwise analyses of data sets from individual subjects, utilizing generalized linear model approach, revealed significant left amygdala activation in response to yohimbine across all PG subjects. This amygdala effect was not observed in the five control individuals. Yohimbine elicited subjective stress ratings in both groups with greater (albeit not statically significantly) average response in the PG subjects. On the other hand, yohimbine did not induce urges to gamble.ConclusionsThe present data support the hypothesis of brain sensitization to pharmacologically-induced stress in PG.

The neural substrates of social emotion perception and regulation are modulated by adult attachment style

Adult attachment style (AAS) refers to individual differences in the way people experience and regulate their social relationships and corresponding emotions. Based on developmental and psychological research, it has been hypothesized that avoidant attachment style (AV) entails deactivating strategies in social contexts, whereas anxious attachment style (AX) involves hyper vigilance and up-regulation mechanisms. However, the neural substrates of differences in social emotion regulation associated with AAS have not been systematically investigated. Here we used fMRI in 19 healthy adults to investigate the effect of AAS on the processing of pleasant or unpleasant social and nonsocial scenes. Participants were asked either to naturally attend (NAT), cognitively reappraise (REAP), or behaviorally suppress (ESUP) their emotional responses. Avoidantly attached participants showed increased prefrontal and anterior cingulate activation to social negative scenes when making spontaneous emotion judgments. They also exhibited persistent increases in dorsolateral prefrontal cortex and left amygdala activity for the same stimuli during reappraisal, as well as additional activation in supplementary motor area and ventral caudate during the suppression of social positive emotions. These results suggest that AV may imply less efficient reappraisal strategies to regulate social negative emotions, and lead to higher conflict or effortful control when suppression cannot be employed. In contrast, anxiously attached participants showed differential increases in the right amygdala and left parahippocampal cortex for social negative and positive stimuli, respectively, but only when making spontaneous emotion judgments. No effect of AX was found during down-regulation conditions. This suggests heightened arousal to negative information without difficulty in down-regulating emotions through cognitive re-evaluation or suppression. Taken together, these findings reveal for the first time the neural underpinnings of attachment-related differences in social emotion regulation.

The Sensitivity of Physiological Measures to Phobic and Nonphobic Fear Intensity

We investigated whether amygdala activation, autonomic responses, respiratory responses, and facial muscle activity (measured over the brow and cheek [fear grin] regions) are all sensitive to phobic versus nonphobic fear and, more importantly, whether effects in these variables vary as a function of both phobic and nonphobic fear intensity. Spider-phobic and comparably low spider-fearful control participants imagined encountering different animals and rated their subjective fear while their central and peripheral nervous system activity was measured. All measures included in our study were sensitive to variations in subjective fear, but were related to different ranges and positions on the subjective fear level continuum. Left amygdala activation, heart rate, and facial muscle activity over the cheek region captured fear intensity variations even within narrowly described regions on the fear level continuum (here within extremely low levels of fear and within considerable phobic fear). Skin conductance and facial muscle activity over the brow region did not capture fear intensity variations within low levels of fear: skin conductance mirrored only extreme levels of fear, and activity over the brow region distinguished phobic from nonphobic fear but also low-to-moderate and high phobic fear. Finally, respiratory measures distinguished phobic from nonphobic fear with no further differentiation within phobic and nonphobic fear. We conclude that a careful consideration of the measures to be used in an investigation and the population to be examined can be critical in order to obtain significant results.

Pregabalin effects on neural response to emotional faces

Pregabalin has shown promise in the treatment of anxiety disorders. Previous functional magnetic resonance imaging (fMRI) studies indicate agents used to treat anxiety, e.g., SSRIs and benzodiazepines, attenuate amygdala, insula, and medial prefrontal cortex (mPFC) activation during emotional processing. Our prior study has shown that during anticipation of an emotional stimulus, pregabalin attenuates amygdala and insula activation but increases medial PFC activation. In this study, we examined whether, similar to SSRIs and benzodiazepines, pregabalin attenuates amygdala, insula, and medial PFC during emotional face processing. Sixteen healthy volunteers underwent a double-blind within-subjects fMRI study investigating effects of placebo, 50 mg, and 200 mg pregabalin on neural activation during an emotional face-matching task. Linear mixed model analysis revealed that pregabalin dose-dependently attenuated left amygdala activation during fearful face-matching and left anterior insula activation during angry face-matching. The 50 mg dose exhibited more robust effects than the 200 mg dose in the right anterior insula and ventral ACC. Thus, pregabalin shares some similarity to SSRIs and benzodiazepines in attenuating anger and fear-related insula and amygdala activation during emotional face processing. However, there is evidence that a subclinical 50 mg dose of pregabalin produced more robust and widespread effects on neural responses in this paradigm than the more clinically relevant 200 mg dose. Taken together, pregabalin has a slightly different effect on brain activation as it relates to anticipation and emotional face processing, which may account for its unique characteristic as an agent for the treatment of anxiety disorders.