Human Amygdala Tracks a Feature-Based Valence Signal Embedded within the Facial Expression of Surprise.

Human amygdala function has been traditionally associated with processing the affective valence (negative vs positive) of an emotionally charged event, especially those that signal fear or threat. However, this account of human amygdala function can be explained by alternative views, which posit that the amygdala might be tuned to either (1) general emotional arousal (activation vs deactivation) or (2) specific emotion categories (fear vs happy). Delineating the pure effects of valence independent of arousal or emotion category is a challenging task, given that these variables naturally covary under many circumstances. To circumvent this issue and test the sensitivity of the human amygdala to valence values specifically, we measured the dimension of valence within the single facial expression category of surprise. Given the inherent valence ambiguity of this category, we show that surprised expression exemplars are attributed valence and arousal values that are uniquely and naturally uncorrelated. We then present fMRI data from both sexes, showing that the amygdala tracks these consensus valence values. Finally, we provide evidence that these valence values are linked to specific visual features of the mouth region, isolating the signal by which the amygdala detects this valence information.SIGNIFICANCE STATEMENT There is an open question as to whether human amygdala function tracks the valence value of cues in the environment, as opposed to either a more general emotional arousal value or a more specific emotion category distinction. Here, we demonstrate the utility of surprised facial expressions because exemplars within this emotion category take on valence values spanning the dimension of bipolar valence (positive to negative) at a consistent level of emotional arousal. Functional neuroimaging data showed that amygdala responses tracked the valence of surprised facial expressions, unconfounded by arousal. Furthermore, a machine learning classifier identified particular visual features of the mouth region that predicted this valence effect, isolating the specific visual signal that might be driving this neural valence response.

Neuroimaging and Anxiety: the Neural Substrates of Pathological and Non-pathological Anxiety.

Advances in the use of noninvasive neuroimaging to study the neural correlates of pathological and non-pathological anxiety have shone new light on the underlying neural bases for both the development and manifestation of anxiety. This review summarizes the most commonly observed neural substrates of the phenotype of anxiety. We focus on the neuroimaging paradigms that have shown promise in exposing this relevant brain circuitry. In this way, we offer a broad overview of how anxiety is studied in the neuroimaging laboratory and the key findings that offer promise for future research and a clearer understanding of anxiety.

Interactions between transient and sustained neural signals support the generation and regulation of anxious emotion.

Anxious emotion can manifest on brief (threat response) and/or persistent (chronic apprehension and arousal) timescales, and prior work has suggested that these signals are supported by separable neural circuitries. This fMRI study utilized a mixed block-event-related emotional provocation paradigm in 55 healthy participants to simultaneously measure brief and persistent anxious emotional responses, testing the specificity of, and interactions between, these potentially distinct systems. Results indicated that components of emotional processing networks were uniquely sensitive to transient and sustained anxious emotion. Whereas the amygdala and midbrain showed only transient responses, the ventral basal forebrain and anterior insula showed sustained activity during extended emotional contexts that tracked positively with task-evoked anxiety. States of lesser anxiety were associated with greater sustained activity in the ventromedial prefrontal cortex. Furthermore, ventromedial prefrontal recruitment was lower in individuals with higher scores on intolerance of uncertainty measures, and this hyporecruitment predicted greater transient amygdala responding to potential threat cues. This work demonstrates how brain circuitries interact across temporal scales to support brief and persistent anxious emotion and suggests potentially divergent mechanisms of dysregulation in clinical syndromes marked by brief versus persistent symptoms of anxiety.

Neural responses to ambiguity involve domain-general and domain-specific emotion processing systems.

Extant research has examined the process of decision making under uncertainty, specifically in situations of ambiguity. However, much of this work has been conducted in the context of semantic and low-level visual processing. An open question is whether ambiguity in social signals (e.g., emotional facial expressions) is processed similarly or whether a unique set of processors come on-line to resolve ambiguity in a social context. Our work has examined ambiguity using surprised facial expressions, as they have predicted both positive and negative outcomes in the past. Specifically, whereas some people tended to interpret surprise as negatively valenced, others tended toward a more positive interpretation. Here, we examined neural responses to social ambiguity using faces (surprise) and nonface emotional scenes (International Affective Picture System). Moreover, we examined whether these effects are specific to ambiguity resolution (i.e., judgments about the ambiguity) or whether similar effects would be demonstrated for incidental judgments (e.g., nonvalence judgments about ambiguously valenced stimuli). We found that a distinct task control (i.e., cingulo-opercular) network was more active when resolving ambiguity. We also found that activity in the ventral amygdala was greater to faces and scenes that were rated explicitly along the dimension of valence, consistent with findings that the ventral amygdala tracks valence. Taken together, there is a complex neural architecture that supports decision making in the presence of ambiguity: (a) a core set of cortical structures engaged for explicit ambiguity processing across stimulus boundaries and (b) other dedicated circuits for biologically relevant learning situations involving faces.

Anxiety dissociates dorsal and ventral medial prefrontal cortex functional connectivity with the amygdala at rest.

Anxiety is linked to compromised interactions between the amygdala and the dorsal and ventral medial prefrontal cortex (mPFC). While numerous task-based neuroimaging studies show that anxiety levels predict amygdala-mPFC connectivity and response magnitude, here we tested the hypothesis that anxiety would predict functional connectivity between these brain regions even during rest. Resting-state functional magnetic resonance imaging scans and self-reported measures of anxiety were acquired from healthy subjects. At rest, individuals with high anxiety were characterized by negatively correlated amygdala-ventral mPFC functional connectivity, while low anxious subjects showed positively correlated activity. Further, high anxious subjects showed amygdala-dorsal mPFC activity that was uncorrelated, while low anxious subjects showed negatively correlated activity. These data show that amygdala-mPFC connectivity at rest indexes normal individual differences in anxiety.

Individual differences in neural activity during a facial expression vs. identity working memory task.

Facial expressions of emotion constitute a critical portion of our non-verbal social interactions. In addition, the identity of the individual displaying this expression is critical to these interactions as they embody the context in which these expressions will be interpreted. To identify any overlapping and/or unique brain circuitry involved in the processing of these two information streams in a laboratory setting, participants performed a working memory (WM) task (i.e., n-back) in which they were instructed to monitor either the expression (EMO) or the identity (ID) of the same set of face stimuli. Consistent with previous work, during both the EMO and ID tasks, we found a significant increase in activity in dorsolateral prefrontal cortex (DLPFC) supporting its generalized role in WM. Further, individuals that showed greater DLPFC activity during both tasks also showed increased amygdala activity during the EMO task and increased lateral fusiform gyrus activity during the ID task. Importantly, the level of activity in these regions significantly correlated with performance on the respective tasks. These findings provide support for two separate neural circuitries, both involving the DLPFC, supporting working memory for the faces and expressions of others.

Age- and gender-related changes in the normal human brain using hybrid diffusion imaging (HYDI).

Diffusion tensor imaging has been widely used to study brain diseases, disorders, development, and aging. However, few studies have explored the effects of aging on diffusion imaging measures with higher b values. Further, the water diffusion in biological tissues appears biexponential, although this also has not been explored with aging. In this study, hybrid diffusion imaging (HYDI) was used to study 52 healthy subjects with an age range from 18 to 72 years. The HYDI diffusion-encoding scheme consisted of five concentric q-space shells with b values ranging from 0 to 9375 s/mm(2). Quantitative diffusion measures were investigated as a function of age and gender using both region-of-interest (whole-brain white matter, genu and splenium of corpus callosum, posterior limb of the internal capsule) and whole-brain voxel-based analyses. Diffusion measures included measures of the diffusion probability density function (zero displacement probability and mean-squared displacement), biexponential diffusion (i.e., volume fractions of fast/slow diffusion compartments and fast/slow diffusivities), and DTI measures (fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity). The biexponential volume fraction, the fast diffusivity, and the axial diffusivity measures (f(1), D(1), and D(a)) were found to be more sensitive to normal aging than the restricted, slow and radial diffusion measures (P(0), D(2), and D(r)). The biexponential volume fraction, f(1), showed the most widespread age dependence in the voxel-based analyses, although both FA and mean diffusivity did show changes in frontal white matter regions that may be associated with age-related decline.

Differentially tuned responses to restricted versus prolonged awareness of threat: a preliminary fMRI investigation.

Responses to threat occur via two known independent processing routes. We propose that early, reflexive processing is predominantly tuned to the detection of congruent combinations of facial cues that signal threat, whereas later, reflective processing is predominantly tuned to incongruent combinations of threat. To test this prediction, we examined responses to threat-gaze expression pairs (anger versus fear expression by direct versus averted gaze). We report on two functional magnetic resonance imaging (fMRI) studies, one employing prolonged presentations (2s) of threat-gaze pairs to allow for reflective processing (Study 1), and one employing severely restricted (33 ms), backward masked presentations of threat-gaze pairs to isolate reflexive neural responding (Study 2). Our findings offer initial support for the conclusion that early, reflexive responses to threat are predominantly tuned to congruent threat-gaze pairings, whereas later reflective responses are predominantly tuned to ambiguous threat-gaze pairings. These findings highlight a distinct dual function in threat perception.

Regional response differences across the human amygdaloid complex during social conditioning.

The amygdala is consistently implicated in biologically relevant learning tasks such as Pavlovian conditioning. In humans, the ability to identify individual faces based on the social outcomes they have predicted in the past constitutes a critical form of associative learning that can be likened to "social conditioning." To capture such learning in a laboratory setting, participants learned about faces that predicted negative, positive, or neutral social outcomes. Participants reported liking or disliking the faces in accordance with their learned social value. During acquisition, we observed differential functional magnetic resonance imaging activation across the human amygdaloid complex consistent with previous lesion, electrophysiological, and functional neuroimaging data. A region of the medial ventral amygdala and a region of the dorsal amygdala/substantia innominata showed signal increases to both Negative and Positive faces, whereas a lateral ventral region displayed a linear representation of the valence of faces such that Negative > Positive > Neutral. This lateral ventral locus also differed from the dorsal and medial loci in that the magnitude of these responses was more resistant to habituation. These findings document a role for the human amygdala in social learning and reveal coarse regional dissociations in amygdala activity that are consistent with previous human and nonhuman animal data.

The structural integrity of an amygdala-prefrontal pathway predicts trait anxiety.

Here, we used diffusion tensor imaging (DTI) and showed that the strength of an axonal pathway identified between the amygdala and prefrontal cortex predicted individual differences in trait anxiety. A functional magnetic resonance imaging (fMRI) functional localizer that has been shown to produce reliable amygdala activation was collected in 20 psychiatrically healthy subjects. Voxelwise regression analyses using this fMRI amygdala reactivity as a regressor were performed on fractional anisotropy images derived from DTI. This analysis identified a white matter pathway between the amygdala and ventromedial prefrontal cortex. Individual differences in the structural integrity of this putative amygdala-prefrontal pathway were inversely correlated with trait anxiety levels (i.e., higher pathway strength predicted lower anxiety). More generally, this study illustrates a strategy for combining fMRI and DTI to identify individual differences in structural pathways that predict behavioral outcomes.

The primacy of negative interpretations when resolving the valence of ambiguous facial expressions.

Low-spatial-frequency (LSF) visual information is processed in an elemental fashion before a finer analysis of high-spatial-frequency information. Further, the amygdala is particularly responsive to LSF information contained within negative (e.g., fearful) facial expressions. In a separate line of research, it has been shown that surprised facial expressions are ambiguous in that they can be interpreted as either negatively or positively valenced. More negative interpretations of surprise are associated with increased ventral amygdala activity. In this report, we show that LSF presentations of surprised expressions bias the interpretation of surprised expressions in a negative direction, a finding suggesting that negative interpretations are first and fast during the resolution of ambiguous valence. We also examined the influence of subjects' positivity-negativity bias on this effect.

Preliminary report on the association between pulvinar volume and the ability to detect backward-masked facial features.

Although backward masking is a powerful experimental tool in mitigating visual awareness of facial expressions of emotion, ~20% of participants consistently report being resistant to its effects. In our previous studies, we excluded these participants from analysis as we focused on neural data in individuals who were subjectively unaware of backward-masked facial features that were presented for a brief period of time (e.g., 17ms). Here, we shifted our focus to potential structural brain difference between aware and unaware participants. To achieve this, structural magnetic resonance imaging (sMRI) data were pooled from two recent backward masking studies of emotional faces or eye whites (Kim et al., 2016, 2010). Out of a total of 64 participants, 12 reported being subjectively aware of the masked faces or their facial features. Whole-brain, voxel-based morphometric analysis of structural MRI data yielded significantly greater volume of the posterior thalamus, including the bilateral pulvinar, for the subjectively aware versus unaware individuals. No other brain region showed significant volumetric differences between groups. The present findings offer a neuroanatomical basis for visual awareness of emotional content in the form of backward-masked facial features, which complements the known functional role of the pulvinar in such neurobehavioral processes.

The uncertainty of it all.

The amygdala is clearly implicated in the processing of biologically relevant stimuli, particularly those that can lead to a state of fear. A new study by Herry, Bach and colleagues using both mouse and human subjects seemingly throws a wrench in the spokes by demonstrating that the amygdala is sensitive to non-biologically relevant stimuli (i.e. tones) when they occur in an unpredictable fashion. The implications of this finding for understanding the role of the amygdala in vigilance, threat assessment and anxiety are considered here.

A Mathematical Model Captures the Structure of Subjective Affect.

Although it is possible to observe when another person is having an emotional moment, we also derive information about the affective states of others from what they tell us they are feeling. In an effort to distill the complexity of affective experience, psychologists routinely focus on a simplified subset of subjective rating scales (i.e., dimensions) that capture considerable variability in reported affect: reported valence (i.e., how good or bad?) and reported arousal (e.g., how strong is the emotion you are feeling?). Still, existing theoretical approaches address the basic organization and measurement of these affective dimensions differently. Some approaches organize affect around the dimensions of bipolar valence and arousal (e.g., the circumplex model), whereas alternative approaches organize affect around the dimensions of unipolar positivity and unipolar negativity (e.g., the bivariate evaluative model). In this report, we (a) replicate the data structure observed when collected according to the two approaches described above, and reinterpret these data to suggest that the relationship between each pair of affective dimensions is conditional on valence ambiguity, and (b) formalize this structure with a mathematical model depicting a valence ambiguity dimension that decreases in range as arousal decreases (a triangle). This model captures variability in affective ratings better than alternative approaches, increasing variance explained from ~60% to over 90% without adding parameters.

Intolerance of uncertainty predicts increased striatal volume.

Oversensitivity to uncertain future threat is usefully conceptualized as intolerance of uncertainty (IU). Neuroimaging studies of IU to date have largely focused on its relationship with brain function, but few studies have documented the association between IU and the quantitative properties of brain structure. Here, we examined potential gray and white-matter brain structural correlates of IU from 61 healthy participants. Voxel-based morphometric analysis highlighted a robust positive correlation between IU and striatal volume, particularly the putamen. Conversely, tract-based spatial statistical analysis showed no evidence for a relationship between IU and the structural integrity of white-matter fiber tracts. Current results converge upon findings from individuals with anxiety disorders such as obsessive-compulsive disorder (OCD) or generalized anxiety disorder (GAD), where abnormally increased IU and striatal volume are consistently reported. They also converge with neurobehavioral data implicating the putamen in predictive coding. Most notably, the relationship between IU and striatal volume is observed at a preclinical level, suggesting that the volumetric properties of the striatum reflect the processing of uncertainty per se as it relates to this dimensional personality characteristic. Such a relationship could then potentially contribute to the onset of OCD or GAD, rather than being unique to their pathophysiology. (PsycINFO Database Record

A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder.

BACKGROUND: Previous functional neuroimaging studies have demonstrated exaggerated amygdala responses and diminished medial prefrontal cortex responses during the symptomatic state in posttraumatic stress disorder (PTSD). OBJECTIVES: To determine whether these abnormalities also occur in response to overtly presented affective stimuli unrelated to trauma; to examine the functional relationship between the amygdala and medial prefrontal cortex and their relationship to PTSD symptom severity in response to these stimuli; and to determine whether responsivity of these regions habituates normally across repeated stimulus presentations in PTSD. DESIGN: Case-control study. SETTING: Academic medical center. PARTICIPANTS: Volunteer sample of 13 men with PTSD (PTSD group) and 13 trauma-exposed men without PTSD (control group). MAIN OUTCOME MEASURES: We used functional magnetic resonance imaging (fMRI) to study blood oxygenation level-dependent signal during the presentation of emotional facial expressions. RESULTS: The PTSD group exhibited exaggerated amygdala responses and diminished medial prefrontal cortex responses to fearful vs happy facial expressions. In addition, in the PTSD group, blood oxygenation level-dependent signal changes in the amygdala were negatively correlated with signal changes in the medial prefrontal cortex, and symptom severity was negatively related to blood oxygenation level-dependent signal changes in the medial prefrontal cortex. Finally, relative to the control group, the PTSD group tended to exhibit diminished habituation of fearful vs happy responses in the right amygdala across functional runs, although this effect did not exceed our a priori statistical threshold. CONCLUSIONS: These results provide evidence for exaggerated amygdala responsivity, diminished medial prefrontal cortex responsivity, and a reciprocal relationship between these 2 regions during passive viewing of overtly presented affective stimuli unrelated to trauma in PTSD.

Differential effects of cognitive load on subjective versus motor responses to ambiguously valenced facial expressions.

Valence is a principal dimension by which we understand emotional experiences, but oftentimes events are not easily classified as strictly positive or negative. Inevitably, individuals vary in how they tend to interpret the valence of ambiguous situations. Surprised facial expressions are one example of a well-defined, ambiguous affective event that induces trait-like differences in the propensity to form a positive or negative interpretation. To investigate the nature of this affective bias, we asked participants to organize emotional facial expressions (surprised, happy, sad) into positive/negative categories while recording their hand-movement trajectories en route to each response choice. We found that positivity-negativity bias resulted in differential hand movements for modal versus nonmodal response trajectories, such that when an individual categorized a surprised face according to his or her nonmodal interpretation (e.g., a negatively biased individual selecting a positive interpretation), the hand showed an enhanced spatial attraction to the alternative, modal response option (e.g., negative) in the opposite corner of the computer screen (Experiment 1). Critically, we also demonstrate that this asymmetry between modal versus nonmodal response trajectories is mitigated when the valence interpretations are made under a cognitive load, although the frequency of modal interpretations is unaffected by the load (Experiment 2). These data inform a body of seemingly disparate findings regarding the effect of cognitive effort on affective responses, by showing within a single paradigm that varying cognitive load selectively alters the dynamic motor movements involved in indicating affective interpretations, whereas the subjective interpretations themselves remain consistent across variable cognitive loads. (PsycINFO Database Record

Parcellation of Human Amygdala Subfields Using Orientation Distribution Function and Spectral K-means Clustering.

Amygdala plays an important role in fear and emotional learning, which are critical for human survival. Despite the functional relevance and unique circuitry of each human amygdaloid subnuclei, there has yet to be an efficient imaging method for identifying these regions in vivo. A data-driven approach without prior knowledge provides advantages of efficient and objective assessments. The present study uses high angular and high spatial resolution diffusion magnetic resonance imaging to generate orientation distribution function, which bears distinctive microstructural features. The features were extracted using spherical harmonic decomposition to assess microstructural similarity within amygdala subfields are identified via similarity matrices using spectral k-mean clustering. The approach was tested on 32 healthy volunteers and three distinct amygdala subfields were identified including medial, posterior-superior lateral, and anterior-inferior lateral.

Interpreting ambiguous social cues in unpredictable contexts.

Unpredictable environments can be anxiety-provoking and elicit exaggerated emotional responses to aversive stimuli. Even neutral stimuli, when presented in an unpredictable fashion, prime anxiety-like behavior and elicit heightened amygdala activity. The amygdala plays a key role in initiating responses to biologically relevant information, such as facial expressions of emotion. While some expressions clearly signal negative (anger) or positive (happy) events, other expressions (e.g. surprise) are more ambiguous in that they can predict either valence, depending on the context. Here, we sought to determine whether unpredictable presentations of ambiguous facial expressions would bias participants to interpret them more negatively. We used functional magnetic resonance imaging and facial electromyography (EMG) to characterize responses to predictable vs unpredictable presentations of surprised faces. We observed moderate but sustained increases in amygdala reactivity to predictable presentations of surprised faces, and relatively increased amygdala responses to unpredictable faces that then habituated, similar to previously observed responses to clearly negative (e.g. fearful) faces. We also observed decreased corrugator EMG responses to predictable surprised face presentations, similar to happy faces, and increased responses to unpredictable surprised face presentations, similar to angry faces. Taken together, these data suggest that unpredictability biases people to interpret ambiguous social cues negatively.