Amygdala Activation In Response Research Articles

Impact of the tryptophan hydroxylase 1 gene A218C polymorphism on amygdala activity in response to affective facial stimuli in patients with major depressive disorder

Tryptophan hydroxylase-1 (TPH1) is the rate-limiting enzyme in serotonin biosynthesis, and allelic variations at the TPH1 locus have been implicated in the pathophysiology of depression. Using 1.5-Tesla functional magnetic resonance imaging, we investigated the possible relationship between TPH1 A218C polymorphism and amygdala response to negative facial stimuli in 26 right-handed female subjects with major depressive disorder (MDD). Genotyping was performed with the polymerase chain reaction. We found a significant association between A allele of the TPH1 A218C polymorphism and neural activations in response to negative facial stimuli. Subjects with the A allele of the TPH1 A218C polymorphism showed greater brain activity in the bilateral amygdala under the sad vs. the neutral condition compared with subjects homozygous for the C allele. Our results suggest that the A218C polymorphism of the TPH1 gene serves as a modulator of amygdala activity in patients with MDD.

Different fusiform activity to stranger and personally familiar faces in shy and social adults

Although shyness is associated with deficits in different aspects of face processing including face recognition and facial emotions, we know relatively little about the neural correlates of face processing among individuals who are shy. Here we show reduced activation to stranger faces among shy adults in a key brain area involved in face processing. Event-related functional magnetic resonance imaging scans were acquired on 12 shy and 12 social young adults during the rapid presentation of stranger and personally familiar neutral faces. Shy adults exhibited significantly less bilateral activation in the fusiform face area (FFA) in response to stranger faces and significantly greater bilateral activation in the same region to personally familiar faces than their social counterparts. Shy adults also exhibited significantly greater right amygdala activation in response to stranger faces than social adults. Among social adults, stranger faces elicited greater FFA activation than personally familiar faces. Findings suggest that there are distinct patterns of neural activation in the FFA in response to viewing stranger and personally familiar faces among shy and social adults.

Changes in Relative Glucose Metabolic Rate Following Cortisol Administration in Aging Veterans with Posttraumatic Stress Disorder: An FDG-PET Neuroimaging Study

Changes in Relative Glucose Metabolic Rate Following Cortisol Administration in Aging Veterans with Posttraumatic Stress Disorder: An FDG-PET Neuroimaging Study

Impact of the tryptophan hydroxylase 1 gene A218C polymorphism on amygdala activity in response to affective facial stimuli in patients with major depressive disorder

Tryptophan hydroxylase-1 (TPH1) is the rate-limiting enzyme in serotonin biosynthesis, and allelic variations at the TPH1 locus have been implicated in the pathophysiology of depression. Using 1.5-Tesla functional magnetic resonance imaging, we investigated the possible relationship between TPH1 A218C polymorphism and amygdala response to negative facial stimuli in 26 right-handed female subjects with major depressive disorder (MDD). Genotyping was performed with the polymerase chain reaction. We found a significant association between A allele of the TPH1 A218C polymorphism and neural activations in response to negative facial stimuli. Subjects with the A allele of the TPH1 A218C polymorphism showed greater brain activity in the bilateral amygdala under the sad vs. the neutral condition compared with subjects homozygous for the C allele. Our results suggest that the A218C polymorphism of the TPH1 gene serves as a modulator of amygdala activity in patients with MDD.

Elevated striatal and decreased dorsolateral prefrontal cortical activity in response to emotional stimuli in euthymic bipolar disorder: no associations with psychotropic medication load

To examine abnormal patterns of frontal cortical-subcortical activity in response to emotional stimuli in euthymic individuals with bipolar disorder type I in order to identify trait-like, pathophysiologic mechanisms of the disorder. We examined potential confounding effects of total psychotropic medication load and illness variables upon neural abnormalities. We analyzed neural activity in 19 euthymic bipolar and 24 healthy individuals to mild and intense happy, fearful and neutral faces. Relative to healthy individuals, bipolar subjects had significantly increased left striatal activity in response to mild happy faces (p < 0.05, corrected), decreased right dorsolateral prefrontal cortical (DLPFC) activity in response to neutral, mild and intense happy faces, and decreased left DLPFC activity in response to neutral, mild and intense fearful faces (p < 0.05, corrected). Bipolar and healthy individuals did not differ in amygdala activity in response to either emotion. In bipolar individuals, there was no significant association between medication load and abnormal activity in these regions, but a negative relationship between age of illness onset and amygdala activity in response to mild fearful faces (p = 0.007). Relative to those without comorbidities, bipolar individuals with comorbidities showed a trend increase in left striatal activity in response to mild happy faces. Abnormally increased striatal activity in response to potentially rewarding stimuli and decreased DLPFC activity in response to other emotionally salient stimuli may underlie mood instabilities in euthymic bipolar individuals, and are more apparent in those with comorbid diagnoses. No relationship between medication load and abnormal neural activity in bipolar individuals suggests that our findings may reflect pathophysiologic mechanisms of the illness rather than medication confounds. Future studies should examine whether this pattern of abnormal neural activity could distinguish bipolar from unipolar depression.

The Callous and Unemotional Right Amygdala

Adults with psychopathy have lower amygdala activation in response to fear than do adults without psychopathy. To see if these findings are present

Serotonergic genes and amygdala activity in response to negative affective facial stimuli in Korean women

Serotonergic genes have been implicated in mood disorders, alcoholism and certain personality traits. We investigated the possible relationship between several polymorphisms in the serotonin (5-HT) system and amygdala responses to negative facial stimuli in Korean women using functional magnetic resonance imaging. All participants were genotyped with regard to the following polymorphisms: the serotonin transporter-gene-linked polymorphic region (5-HTTLPR), tryptophan hydroxylase 2 (TPH2) G(-703)T, 5-HT(1A) C(-1019)G and 5-HT(2A) single nucleotide polymorphism (SNP) rs6311. We found increased activations in response to angry facial stimuli in the bilateral amygdala of subjects with the long allele of 5-HTTLPR compared with those with two copies of the short allele. Higher activations in response to sad facial stimuli were found in the bilateral amygdala of subjects with the T/T genotype of 5-HT(2A) SNP rs6311, compared with C allele carriers, and in subjects with the G/G genotype of TPH2 G(-703)T, compared with those with T/T and G/T genotypes. Our results for individuals from an Asian population countered a previous finding for a Caucasian population and identified the moderating role of genetic background in the relationships between these serotonergic gene polymorphisms and amygdala function elicited by negative emotional stimuli.

Attention and amygdala activity: an fMRI study with spider pictures in spider phobia

Facilitated detection of threatening visual cues is thought to be adaptive. In theory, detection of threat cues should activate the amygdala independently from allocation of attention. However, previous studies using emotional facial expressions as well as phobic cues yielded contradictory results. We used fMRI to examine whether the allocation of attention to components of superimposed spider and bird displays modulates amygdala activation. Nineteen spider-phobic women were instructed to identify either a moving or a stationary animal in briefly presented double-exposure displays. Amygdala activation followed a dose-response relationship: Compared to congruent neutral displays (two birds), amygdala activation was most pronounced in response to congruent phobic displays (two spiders) and less but still significant in response to mixed displays (spider and bird) when attention was focused on the phobic component. When attention was focused on the neutral component, mixed displays did not result in significant amygdala activation. This was confirmed in a significant parametric graduation of the amygdala activation in the order of congruent phobic displays, mixed displays with attention focus on the spider, mixed displays with focus on the bird and congruent neutral displays. These results challenge the notion that amygdala activation in response to briefly presented phobic cues is independent from attention.

The human amygdala is sensitive to the valence of pictures and sounds irrespective of arousal: an fMRI study

With the advent of studies showing that amygdala responses are not limited to fear-related or highly unpleasant stimuli, studies began to focus on stimulus valence and stimulus-related arousal as predictors of amygdala activity. Recent studies in the chemosensory domain found amygdala activity to increase with the intensity of negative and positive chemosensory stimuli. This has led to the proposal that amygdala activity might be an indicator of emotional arousal, at least in the chemosensory domain. The present study investigated amygdala activity in response to visual and auditory stimuli. By selecting stimuli based on individual valence and arousal ratings, we were able to dissociate stimulus valence and stimulus-related arousal, both on the verbal and the peripheral physiological level. We found that the amygdala was sensitive to stimulus valence even when arousal was controlled for, and that increased amygdala activity was better explained by valence than by arousal. The proposed difference in the relation between amygdala activity and stimulus-related arousal between the chemosensory and the audiovisual domain is discussed in terms of the amygdala's embedding within these sensory systems and the processes by which emotional meaning is derived.

The human amygdala is involved in general behavioral relevance detection: Evidence from an event-related functional magnetic resonance imaging Go-NoGo task

The amygdala is classically regarded as a detector of potential threat and as a critical component of the neural circuitry mediating conditioned fear responses. However, it has been reported that the human amygdala responds to multiple expressions of emotions as well as emotionally neutral stimuli of a novel, uncertain or ambiguous nature. Thus, it has been proposed that the function of the amygdala may be of a more general art, i.e. as a detector of behaviorally relevant stimuli [Sander D, Grafman J, Zalla T (2003) The human amygdala: an evolved system for relevance detection. Rev Neurosci 14:303–316]. To investigate this putative function of the amygdala, we used event related functional magnetic resonance imaging (fMRI) and a modified Go-NoGo task composed of behaviorally relevant and irrelevant letter and number stimuli. Analyses revealed bilateral amygdala activation in response to letter stimuli that were behaviorally relevant as compared with letters with less behavioral relevance. Similar results were obtained for relatively infrequent NoGo relevant stimuli as compared with more frequent Go stimuli. Our findings support a role for the human amygdala in general detection of behaviorally relevant stimuli.

P.1.e.005 Serotonergic genes and amygdala activity in response to negative affective facial stimuli

P.1.e.005 Serotonergic genes and amygdala activity in response to negative affective facial stimuli

Emotional processing in male adolescents with childhood‐onset conduct disorder

Boys with early onset of conduct disorder (CD), most of whom also meet diagnostic criteria of a comorbid attention deficit hyperactivity disorder (ADHD), tend to exhibit high levels of aggression throughout development. While a number of functional neuroimaging studies on emotional processing have been performed in antisocial adults, little is known about how CD children process emotional information. Functional magnetic resonance imaging data were analyzed in 22 male adolescents aged 12 to 17 years with childhood-onset CD (16 of them with comorbid ADHD) compared to 22 age-matched male healthy controls. In order to consider the likely confounding of results through ADHD comorbidity, we performed a supplementary study including 13 adolescent subjects with pure ADHD who were compared with healthy controls. To challenge emotional processing of stimuli, a passive viewing task was applied, presenting pictures of negative, positive or neutral valence. When comparing CD/combined disorder patients with healthy controls, we found enhanced left-sided amygdala activation in response to negative pictures as compared to neutral pictures in the patient group. In addition, these boys exhibited no reduced activation in the orbitofrontal, anterior cingulate and insular cortices. By contrast, children with pure ADHD did not show any abnormalities in amygdala activation but showed decreased neural activity in the insula only in response to negative pictures. Increased rather than reduced amygdala activation found in our study may indicate an enhanced response to environmental cues in adolescents with early-onset CD (most of whom also met the condition of ADHD), and is not consistent with the assumption of a reduced capacity to take note of affective information in the social environment. Further studies with an emphasis on developmental aspects of affect regulation are needed to clarify the relationship between CD and adult personality pathology associated with different modes of persistent antisocial behavior.

The BDNF Val66Met polymorphism affects amygdala activity in response to emotional stimuli: Evidence from a genetic imaging study

Mounting evidence shows that the brain derived neurotrophic factor (BDNF) plays a crucial role in synaptic plasticity. Due to its potential involvement in psychiatric diseases like depression and anxiety disorders BDNF lately became a major target in research. A functional variant of the BDNF gene – the BDNF Val66Met polymorphism – is of particular interest, because it influences the BDNF secretion which is followed by signaling at the TrkB receptor leading to dendritic growth of neurons. Findings from genetic association studies in humans yield heterogenous results with respect to the question of which allele represents a potential risk factor for an affective disorder. Although structural MRT studies revealed that the 66Met variant is associated with smaller hippocampi and could therefore present the risk allele, fMRI studies investigating the processing of emotion with respect to the BDNF Val66Met polymorphism are lacking.N=37 healthy female subjects participated in an fMRI experiment with an affective startle reflex paradigm. Carriers of the 66Met variant showed stronger amygdala activation in the right hemisphere in response to emotional stimuli compared to neutral stimuli. The results of this study add to growing literature, showing that it is the 66Met, which is associated with higher trait anxiety.

Eye-Gaze Direction Modulates Race-Related Amygdala Activity

Although previous research has found greater activity in the human amygdala in response to Black male compared with White male targets, the basis of this effect remains unclear. For example, is it race alone that triggers amygdala activity, or do other stimulus cues, in conjunction with racial group membership, also play a critical role in this regard? To address this issue, we used functional magnetic resonance imaging to measure amygdala activity in response to Black and White male targets displaying different eye-gaze directions (i.e. direct or averted gaze), as gaze cues have been shown to influence the socio-emotional aspects of person construal. The results revealed that eye-gaze direction significantly moderates race-related amygdala activity. Specifically, Black targets only generated greater amygdala activity than White targets when the faces bore direct gaze. This finding is noteworthy as it demonstrates the importance of compound stimulus cues in the appraisal of social targets.

Limbic dysregulation is associated with lowered heart rate variability and increased trait anxiety in healthy adults

We tested whether dynamic interaction between limbic regions supports a control systems model of excitatory and inhibitory components of a negative feedback loop, and whether dysregulation of those dynamics might correlate with trait differences in anxiety and their cardiac characteristics among healthy adults. Sixty-five subjects received fMRI scans while passively viewing angry, fearful, happy, and neutral facial stimuli. Subjects also completed a trait anxiety inventory, and were monitored using ambulatory wake ECG. The ECG data were analyzed for heart rate variability, a measure of autonomic regulation. The fMRI data were analyzed with respect to six limbic regions (bilateral amygdala, bilateral hippocampus, Brodmann Areas 9, 45) using limbic time-series cross-correlations, maximum BOLD amplitude, and BOLD amplitude at each point in the time-series. Diminished coupling between limbic time-series in response to the neutral, fearful, and happy faces was associated with greater trait anxiety, greater sympathetic activation, and lowered heart rate variability. Individuals with greater levels of trait anxiety showed delayed activation of Brodmann Area 45 in response to the fearful and happy faces, and lowered Brodmann Area 45 activation with prolonged left amygdala activation in response to the neutral faces. The dynamics support limbic regulation as a control system, in which dysregulation, as assessed by diminished coupling between limbic time-series, is associated with increased trait anxiety and excitatory autonomic outputs. Trait-anxious individuals showed delayed inhibitory activation in response to overt-affect stimuli and diminished inhibitory activation with delayed extinction of excitatory activation in response to ambiguous-affect stimuli.

Reciprocal Effects of Antidepressant Treatment on Activity and Connectivity of the Mood Regulating Circuit: An fMRI Study

Reciprocal Effects of Antidepressant Treatment on Activity and Connectivity of the Mood Regulating Circuit: An fMRI Study

Influence of comorbid depression on fear in posttraumatic stress disorder: An fMRI study

Posttraumatic Stress Disorder (PTSD) is thought to involve a dysregulation of medial prefrontal–amygdala activity in response to fear. PTSD studies, however, have been confounded by comorbid depression, which shows similar dysregulation. Amygdala and medial prefrontal activity was reduced in PTSD-depression compared to PTSD-alone samples, highlighting the need to account for comorbidity.

The amygdala and the experience of affect

The current study examined the hypothesis that amygdala activation serves as a neural precondition for negative affective experience. Participants' affective experience was measured by asking them to report on their momentary experiences several times a day over the course of a month using an electronic experience-sampling procedure. One year later, participants viewed backwardly masked depictions of fear while functional magnetic resonance imaging was used to measure their amygdala and fusiform gyrus activation. Negative affect, as measured during the experience-sampling procedure 1-year prior, was positively correlated with amygdala activation in response to these brief presentations of fear depictions. Furthermore, descriptive analyses indicated that fusiform gyrus activation and negative affective experience in the scanner were associated for participants reporting increased nervousness during the imaging procedure. The results are consistent with the interpretation that the amygdala contributes to negative affective experience by increasing perceptual sensitivity for negative stimuli.

5-HTTLPR Biases Amygdala Activity in Response to Masked Facial Expressions in Major Depression

The amygdala is a key structure in a limbic circuit involved in the rapid and unconscious processing of facial emotions. Increased amygdala reactivity has been discussed in the context of major depression. Recent studies reported that amygdala activity during conscious emotion processing is modulated by a functional polymorphism in the serotonin transporter gene (5-HTTLPR) in healthy subjects. In the present study, amygdala reactivity to displays of emotional faces was measured by means of fMRI at 3T in 35 patients with major depression and 32 healthy controls. Conscious awareness of the emotional stimuli was prevented via backward-masking to investigate automatic emotion processing. All subjects were genotyped for the 5-HTTLPR polymorphism. Risk allele carriers (S or L(G)) demonstrated increased amygdala reactivity to masked emotional faces, which in turn was significantly correlated with life-time psychiatric hospitalization as an index of chronicity. This might indicate that genetic variations of the serotonin transporter could increase the risk for depression chronification via altering limbic neural activity on a preattentive level of emotion processing.

Amygdala responses to nonlinguistic emotional vocalizations

Whereas there is ample evidence for a role of the amygdala in the processing of visual emotional stimuli, particularly those with negative value, discrepant results have been reported regarding amygdala responses to emotional auditory stimuli. The present study used event-related functional magnetic resonance imaging to investigate cerebral activity underlying processing of emotional nonlinguistic vocalizations, with a particular focus on neural changes in the amygdala. Fourteen healthy volunteers were scanned while performing a gender identification task. Stimuli, previously validated on emotional valence, consisted of positive (happiness and sexual pleasure) and negative (sadness and fear) vocalizations, as well as emotionally neutral sounds (e.g., coughs). Results revealed bilateral amygdala activation in response to all emotional vocalizations when compared to neutral stimuli. These findings suggest that the generally accepted involvement of the amygdala in the perception of emotional visual stimuli, such as facial expressions, also applies to stimuli within the auditory modality. Importantly, this amygdala response was observed for both positive and negative emotional vocalizations.