Amygdala subdivisions exhibit aberrant whole-brain functional connectivity in relation to stress intolerance and psychotic symptoms in 22q11.2DS.

The amygdala is a key region in emotional regulation, which is often impaired in psychosis. However, it is unclear if amygdala dysfunction directly contributes to psychosis, or whether it contributes to psychosis through symptoms of emotional dysregulation. We studied the functional connectivity of amygdala subdivisions in patients with 22q11.2DS, a known genetic model for psychosis susceptibility. We investigated how dysmaturation of each subdivision's connectivity contributes to positive psychotic symptoms and impaired tolerance to stress in deletion carriers. Longitudinally-repeated MRI scans from 105 patients with 22q11.2DS (64 at high-risk for psychosis and 37 with impaired tolerance to stress) and 120 healthy controls between the ages of 5 to 30 years were included. We calculated seed-based whole-brain functional connectivity for amygdalar subdivisions and employed a longitudinal multivariate approach to evaluate the developmental trajectory of functional connectivity across groups. Patients with 22q11.2DS presented a multivariate pattern of decreased basolateral amygdala (BLA)-frontal connectivity alongside increased BLA-hippocampal connectivity. Moreover, associations between developmental drops in centro-medial amygdala (CMA)-frontal connectivity to both impaired tolerance to stress and positive psychotic symptoms in deletion carriers were detected. Superficial amygdala hyperconnectivity to the striatum was revealed as a specific pattern arising in patients who develop mild to moderate positive psychotic symptoms. Overall, CMA-frontal dysconnectivity was found as a mutual neurobiological substrate in both impaired tolerance to stress and psychosis, suggesting a role in prodromal dysregulation of emotions in psychosis. While BLA dysconnectivity was found to be an early finding in patients with 22q11.2DS, which contributes to impaired tolerance to stress.

Mixed emotions to social situations: An fMRI investigation.

BACKGROUND: Neuroscience research has generally studied emotions each taken in isolation. However, mixed emotional states (e.g., the co-occurrence of amusement and disgust, or sadness and pleasure) are common in everyday life. Psychophysiological and behavioral evidence suggests that mixed emotions may have response profiles that are distinguishable from their constituent emotions. Yet, the brain bases of mixed emotions remain unresolved. METHODS: We recruited 38 healthy adults who viewed short, validated film clips, eliciting either positive (amusing), negative (disgusting), neutral, or mixed (a mix of amusement and disgust) emotional states, while brain activity was assessed by functional magnetic resonance imaging (fMRI). We assessed mixed emotions in two ways: first by comparing neural reactivity to ambiguous (mixed) with that to unambiguous (positive and negative) film clips and second by conducting parametric analyses to measure neural reactivity with respect to individual emotional states. We thus obtained self-reports of amusement and disgust after each clip and computed a minimum feeling score (shared minimum of amusement and disgust) to quantify mixed emotional feelings. RESULTS: Both analyses revealed a network of the posterior cingulate (PCC), medial superior parietal lobe (SPL)/precuneus, and parieto-occipital sulcus to be involved in ambiguous contexts eliciting mixed emotions. CONCLUSION: Our results are the first to shed light on the dedicated neural processes involved in dynamic social ambiguity processing. They suggest both higher-order (SPL) and lower-order (PCC) processes may be needed to process emotionally complex social scenes.

Identifying Disease-Specific Neural Reactivity to Psychosocial Stress in Borderline Personality Disorder.

BACKGROUND: Patients with borderline personality disorder (BPD) typically present emotion dysregulation (ED) when faced with adversity. However, it is argued that altered stress response may be more influenced by ED than BPD-specific traits. Here, we investigated this issue with functional magnetic resonance imaging using another ED condition as clinical control, i.e., bipolar disorder (BD), and controlling for ED traits. METHODS: We recruited 17 patients with BD, 24 patients with BPD, and 32 healthy control (HC) subjects. We adapted a functional magnetic resonance imaging-compatible psychosocial stressor task (Montreal Imaging Stress Task) in which participants are placed under time pressure when performing mental calculations and then receive immediate performance feedback (positive, negative, and neutral). ED traits were measured via self-report questionnaires targeting cognitive emotion dysregulation, affective lability, and trait anger and anxiety. RESULTS: Relative to patients with BD and HC subjects, patients with BPD exhibited overactive corticolimbic reactivity across all conditions, particularly in self-monitoring and emotion regulation regions such as the orbitofrontal cortex and anterior insula, even when controlling for ED. Conversely, patients with BD exhibited hypoactive corticolimbic reactivity to all feedback conditions compared with patients with BPD and HC subjects, even after controlling for ED. HC subjects exhibited significantly lower amygdala/hippocampus activity compared with both clinical groups, although this did not survive when controlling for ED. CONCLUSIONS: This study provides new insight into BPD-specific neural stress responding, suggesting hyperactive self- and emotion-regulatory neural psychosocial stress responding, independent of ED traits. The findings also highlight the importance of considering BPD as a diagnostic profile distinguishable from other ED disorder clinical groups.

Maladaptive emotion regulation traits predict altered corticolimbic recovery from psychosocial stress.

BACKGROUND: Adaptive recovery from stress promotes healthy cognitive affective functioning, whereas maladaptive recovery is linked to poor psychological outcomes. Neural regions, like the anterior cingulate and hippocampus, play critical roles in psychosocial stress responding and serve as hubs in the corticolimbic neural system. To date, however, it is unknown how cognitive emotion regulation traits (cER), adaptive and maladaptive, influence corticolimbic stress recovery. Here, we examined acute psychosocial stress neural recovery, accounting for cER. METHODS: Functional neuroimaging data were collected while forty-seven healthy participants performed blocks of challenging, time-sensitive, mental calculations. Participants immediately received performance feedback (positive/negative/neutral) and their ranking, relative to fictitious peers. Participants rested for 90 seconds after each feedback, allowing for a neural stress recovery period. Collected before scanning, cER scores were correlated with neural activity during each recovery condition. RESULTS: Negative feedback recovery yielded increased activity within the dorsomedial prefrontal cortex and amygdala, but this effect was ultimately explained by maladaptive cER (M-cER), like rumination. Isolating positive after-effects (i.e. positive > negative recovery) yielded a significant positive correlation between M-cER and the anterior cingulate, anterior insula, hippocampus, and striatum. CONCLUSIONS: We provide first evidence of M-cER to predict altered neural recovery from positive stress within corticolimbic regions. Positive feedback may be potentially threatening to individuals with poor stress regulation. Identifying positive stress-induced activation patterns in corticolimbic neural networks linked to M-cER creates the possibility to identify these neural responses as risk factors for social-emotional dysregulation subsequent to rewarding social information, often witnessed in affective disorders, like depression.

Temporal dynamics of amygdala response to emotion- and action-relevance.

It has been proposed that the human amygdala may not only encode the emotional value of sensory events, but more generally mediate the appraisal of their relevance for the individual's goals, including relevance for action or task-based needs. However, emotional and non-emotional/action-relevance might drive amygdala activity through distinct neural signals, and the relative timing of both kinds of responses remains undetermined. Here, we recorded intracranial event-related potentials from nine amygdalae of patients undergoing epilepsy surgery, while they performed variants of a Go/NoGo task with faces and abstract shapes, where emotion- and action-relevance were orthogonally manipulated. Our results revealed early amygdala responses to emotion facial expressions starting ~ 130 ms after stimulus-onset. Importantly, the amygdala responded to action-relevance not only with face stimuli but also with abstract shapes (squares), and these relevance effects consistently occurred in later time-windows (starting ~ 220 ms) for both faces and squares. A similar dissociation was observed in gamma activity. Furthermore, whereas emotional responses habituated over time, the action-relevance effect increased during the course of the experiment, suggesting progressive learning based on the task needs. Our results support the hypothesis that the human amygdala mediates a broader relevance appraisal function, with the processing of emotion-relevance preceding temporally that of action-relevance.

Interoceptive active inference and self-representation in social anxiety disorder (SAD): exploring the neurocognitive traits of the SAD self.

This article provides an interoceptive active inference (IAI) account of social anxiety disorder (SAD). Through a neurocognitive framework, we argue that the cognitive and behavioural profile of SAD is best conceived of as a form of maladaptive IAI produced by a negatively biased self-model that cannot reconcile inconsistent tendencies to approach and avoid social interaction. Anticipated future social interactions produce interoceptive prediction error (bodily states of arousal). These interoceptive states are transcribed and experienced as states of distress due to the influence of inconsistent and unstable self-models across a hierarchy of interrelated systems involved in emotional, interoceptive and affective processing. We highlight the role of the insula cortex, in concert with the striatum, amygdala and dorsal anterior cingulate in the generation and reduction of interoceptive prediction errors as well as the resolution of social approach-avoidance conflict. The novelty of our account is a shift in explanatory priority from the representation of the social world in SAD to the representation of the SAD self. In particular, we show how a high-level conceptual self-model of social vulnerability and inadequacy fails to minimize prediction errors produced by a basic drive for social affiliation combined with strong avoidant tendencies. The result is a cascade of interoceptive prediction errors whose attempted minimization through action (i.e. active inference) yields the symptom profile of SAD. We conclude this article by proposing testable hypotheses to further investigate the neurocognitive traits of the SAD self with respect to IAI.

When at rest: "Event-free" active inference may give rise to implicit self-models of coping potential.

Kalisch and colleagues highlight coping potential (CP) as a principle resilience mechanism during event engagement. We complement this discussion by exploring generative implicit CP self-models, arguably emerging during "resting-state," subsequent and prior to events. Resting-state affords a propitious environment for Bayesian learning, wherein appraisals/reappraisals may update active inferential CP self-models, which then mediate appraisal style organization and resilience factor valuation.

Functional connectivity mapping of regions associated with self- and other-processing.

Neuroscience literature increasingly suggests a conceptual self composed of interacting neural regions, rather than independent local activations, yet such claims have yet to be investigated. We, thus, combined task-dependent meta-analytic connectivity modeling (MACM) with task-independent resting-state (RS) connectivity analysis to delineate the neural network of the self, across both states. Given psychological evidence implicating the self's interdependence on social information, we also delineated the neural network underlying conceptual other-processing. To elucidate the relation between the self-/other-networks and their function, we mined the MACM metadata to generate a cognitive-behavioral profile for an empirically identified region specific to conceptual self, the pregenual anterior cingulate (pACC), and conceptual other, posterior cingulate/precuneus (PCC/PC). Mining of 7,200 published, task-dependent, neuroimaging studies, using healthy human subjects, yielded 193 studies activating the self-related seed and were conjoined with RS connectivity analysis to delineate a differentiated self-network composed of the pACC (seed) and anterior insula, relative to other functional connectivity. Additionally, 106 studies activating the other-related seed were conjoined with RS connectivity analysis to delineate a differentiated other-network of PCC/PC (seed) and angular gyrus/temporoparietal junction, relative to self-functional connectivity. The self-network seed related to emotional conflict resolution and motivational processing, whereas the other-network seed related to socially oriented processing and contextual information integration. Notably, our findings revealed shared RS connectivity between ensuing self-/other-networks within the ventromedial prefrontal cortex and medial orbitofrontal cortex, suggesting self-updating via integration of self-relevant social information. We, therefore, present initial neurobiological evidence corroborating the increasing claims of an intricate self-network, the architecture of which may promote social value processing.

The functional profile of the human amygdala in affective processing: insights from intracranial recordings.

The amygdala is suggested to serve as a key structure in the emotional brain, implicated in diverse affective processes. Still, the bulk of existing neuroscientific investigations of the amygdala relies on conventional neuroimaging techniques such as fMRI, which are very useful but subject to limitations. These limitations are particular to their temporal resolution, but also to their spatial precision at a very fine-grained level. Here, we review studies investigating the functional profile of the human amygdala using intracranial electroencephalography (iEEG), an invasive technique with high temporal and spatial precision. We conducted a systematic literature review of 47 iEEG studies investigating the human amygdala, and we focus on two content-related domains and one process-related domain: (1) memory formation and retrieval; (2) affective processing; and (3) latency components. This review reveals the human amygdala to engage in invariant semantic encoding and recognition of specific objects and individuals, independent of context or visuospatial attributes, and to discriminate between familiar and novel stimuli. The review highlights the amygdala's role in emotion processing witnessed in differential treatment of social-affective facial cues, differential neuronal firing to relevant novel stimuli, and habituation to familiar affective stimuli. Overall, the review suggests the amygdala plays a key role in the processing of affective relevance. Finally, this review delineates effects on amygdala neuronal activity into three time latency windows (post-stimulus onset). The early window (∼ 5 0-290 msec) subsumes effects respective to exogenous stimulus-driven affective processing of faces and emotion. The intermediate window (∼ 270-470 msec) comprises effects related to explicit attention to novel task-relevant stimuli, irrespective of sensory modality. The late window (∼ 600-1400 msec) subsumes effects from tasks soliciting semantic associations and working memory during affective processing. We juxtapose these iEEG data with current clinical topics relevant to amygdala activation and propose avenues for future investigation of the amygdala using iEEG methods.

Degrees of separation: a quantitative neuroimaging meta-analysis investigating self-specificity and shared neural activation between self- and other-reflection.

In functional neuroimaging studies, self-specificity has been investigated by contrasting other-relevant processing against the self. Our meta-analysis investigates self-specificity with respect to degrees of self-relatedness (SR) of the other (i.e. close and public other). Literature suggests a dorsal-ventral component of self- and other-reflection within the MPFC, which has yet to be analyzed according to varying SR, nor has it been quantified statistically. In the present meta-analysis, we pursued three main objectives. First, we conducted whole-brain ALE meta-analyses using contemporary literature analyzing self>close other and self>public other contrasts to determine self-specific regions sensitive to SR. Next, we conducted ALE and conjunction analyses of studies employing self>control, close other>control, or public other>control contrasts to determine shared regions of activation. Third, we conducted post hoc analyses to quantify any observed dorsal-ventral distinction, employing novel methodology using a surface-based coordinates system. We observed significant activation in the dACC and vACC for self>close other and self>public other, whereas anterior insula was observed only for self>public other. An MPFC dorsal-ventral distinction was observed and quantified whereby public other>control was significantly more dorsal than self>control and close other>control. Our results are discussed with regards to SR. Prospective avenues of research exploiting our methodology are proposed.