The VLPFC-Engaged Voluntary Emotion Regulation: Combined TMS-fMRI Evidence for the Neural Circuit of Cognitive Reappraisal.

A clear understanding of the neural circuit underlying emotion regulation (ER) is important for both basic and translational research. However, a lack of evidence based on combined neuroimaging and neuromodulation techniques calls into question (1) whether the change of prefrontal-subcortical activity intrinsically and causally contributes to the ER effect; and (2) whether the prefrontal control system directly modulates the subcortical affective system. Accordingly, we combined fMRI recordings with transcranial magnetic stimulation (TMS) to map the causal connections between the PFC and subcortical affective structures (amygdala and insula). A total of 117 human adult participants (57 males and 60 females) were included in the study. The results revealed that TMS-induced ventrolateral PFC (VLPFC) facilitation led to enhanced activity in the VLPFC and ventromedial PFC (VMPFC) as well as attenuated activity in the amygdala and insula during reappraisal but not during nonreappraisal (i.e., baseline). Moreover, the activated VLPFC intensified the prefrontal-subcortical couplings via the VMPFC during reappraisal only. This study provides combined TMS-fMRI evidence that downregulating negative emotion involves the prefrontal control system suppressing the subcortical affective system, with the VMPFC serving as a crucial hub within the VLPFC-subcortical network, suggesting an indirect pathway model of the ER circuit. Our findings outline potential protocols for improving ER ability by intensifying the VLPFC-VMPFC coupling in patients with mood and anxiety disorders.SIGNIFICANCE STATEMENT Using fMRI to examine the TMS effect, we uncovered that the opposite neural changes in prefrontal (enhanced) and subcortical (attenuated) regions are not a byproduct of emotion regulation (ER); instead, this prefrontal-subcortical activity per se causally contributes to the ER effect. Furthermore, using TMS to amplify the neural changes within the ER circuit, the "bridge" role of the VMPFC is highlighted under the reappraisal versus nonreappraisal contrast. This "perturb-and-measure" approach overcomes the correlational nature of fMRI data, helping us to identify brain regions that causally support reappraisal (the VLPFC and VMPFC) and those that are modulated by reappraisal (the amygdala and insula). The uncovered ER circuit is important for understanding the neural systems underlying reappraisal and valuable for translational research.

Money or funny: Effective connectivity during service recovery with a DCM-PEB approach.

While monetary compensation is considered the most effective service recovery strategy, relief theory claims that humor may also be useful in service recovery situations. This study investigated the effects of humor in service recovery using dynamic causal modeling and parametric empirical Bayes analysis to identify effective connectivity (EC) patterns in the dopaminergic reward system across four conditions representing different service recovery strategies: monetary compensation and humor (MH), monetary compensation and an apology (MA), non-monetary compensation using humor (H), and non-monetary compensation using an apology (CON, the control condition). The findings support the importance of the nucleus accumbens (NAc) in the monetary compensation (MH and MA) conditions and the amygdala in the non-monetary compensation (H and CON) conditions. Monetary compensation (MH and MA) resulted in right substantia nigra (rSN) to NAc EC, suggesting the processing of recovery satisfaction associated with perceived outcome fairness. Conversely, non-monetary compensation strategies (H and CON) resulted in left substantia nigra (lSN) to amygdala EC, suggesting the processing of satisfaction related to perceived interactional fairness. The use of humor for service recovery resulted in VTA-to-lSN-to-amygdala EC during humor appreciation, while the use of apologies (CON and MA) resulted in lSN-to-amygdala and lSN-to-VTA connectivity. Surprisingly, processing satisfaction in the MH condition did not activate the amygdala during humor appreciation. Coping humor could be norm-violating for service recovery, and its effectiveness depends on multiple factors. The results suggest that monetary compensation, humorous responses, and apologies play key roles in neurological responses to service recovery strategies.

Dissecting the midlife crisis: disentangling social, personality and demographic determinants in social brain anatomy.

In any stage of life, humans crave connection with other people. In midlife, transitions in social networks can relate to new leadership roles at work or becoming a caregiver for aging parents. Previous neuroimaging studies have pinpointed the medial prefrontal cortex (mPFC) to undergo structural remodelling during midlife. Social behavior, personality predisposition, and demographic profile all have intimate links to the mPFC according in largely disconnected literatures. Here, we explicitly estimated their unique associations with brain structure using a fully Bayesian framework. We weighed against each other a rich collection of 40 UK Biobank traits with their interindividual variation in social brain morphology in ~10,000 middle-aged participants. Household size and daily routines showed several of the largest effects in explaining variation in social brain regions. We also revealed male-biased effects in the dorsal mPFC and amygdala for job income, and a female-biased effect in the ventral mPFC for health satisfaction.

Assessment of olfactory information in the human brain using 7-Tesla functional magnetic resonance imaging.

Olfaction could prove to be an early marker of neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. To use olfaction for disease diagnosis, elucidating the standard olfactory functions in healthy humans is necessary. However, the olfactory function in the human brain is less frequently assessed because of methodological difficulties associated with olfactory-related cerebral areas. Using ultra-high fields (UHF), functional magnetic resonance imaging (fMRI) with high spatial resolution and sensitivity may allow for the measurement of activation in the cerebral areas. This study aimed to apply 7-Tesla fMRI to assess olfactory function in the human brain by exposing individuals to four different odorants for 8 s. We found that olfactory stimulation mainly activated the piriform and orbitofrontal cortex in addition to the amygdala. Among these regions, univariate fMRI analysis indicated that subjective odor intensity significantly correlated with the averaged fMRI signals in the piriform cortex but not with subjective hedonic tone in any region. In contrast, multivariate fMRI analysis showed that subjective hedonic tone could be discriminated from the fMRI response patterns in the posterior orbitofrontal cortex. Thus, the piriform cortex is mainly associated with subjective odor intensity, whereas the posterior orbitofrontal cortex are involved in the discrimination of the subjective hedonic tone of the odorant. UHF-fMRI may be useful for assessing olfactory function in the human brain.

Functions of primate amygdala neurons in economic decisions and social decision simulation.

Long implicated in aversive processing, the amygdala is now recognized as a key component of the brain systems that process rewards. Beyond reward valuation, recent findings from single-neuron recordings in monkeys indicate that primate amygdala neurons also play an important role in decision-making. The reward value signals encoded by amygdala neurons constitute suitable inputs to economic decision processes by being sensitive to reward contingency, relative reward quantity and temporal reward structure. During reward-based decisions, individual amygdala neurons encode both the value inputs and corresponding choice outputs of economic decision processes. The presence of such value-to-choice transitions in single amygdala neurons, together with other well-defined signatures of decision computation, indicate that a decision mechanism may be implemented locally within the primate amygdala. During social observation, specific amygdala neurons spontaneously encode these decision signatures to predict the choices of social partners, suggesting neural simulation of the partner's decision-making. The activity of these 'simulation neurons' could arise naturally from convergence between value neurons and social, self-other discriminating neurons. These findings identify single-neuron building blocks and computational architectures for decision-making and social behavior in the primate amygdala. An emerging understanding of the decision function of primate amygdala neurons can help identify potential vulnerabilities for amygdala dysfunction in human conditions afflicting social cognition and mental health.

Prenatal stress exposure and multimodal assessment of amygdala-medial prefrontal cortex connectivity in infants.

Stressful experiences are linked to neurodevelopment. There is growing interest in the role of stress in the connectivity between the amygdala and medial prefrontal cortex (mPFC), a circuit that subserves automatic emotion regulation. However, the specific timing and mechanisms that underlie the association between stress and amygdala-mPFC connectivity are unclear. Many factors, including variations in fetal exposure to maternal stress, appear to affect early developing brain circuitry. However, few studies have examined the associations of stress and amygdala-mPFC connectivity in early life, when the brain is most plastic and sensitive to environmental influence. In this longitudinal pilot study, we characterized the association between prenatal stress and amygdala-mPFC connectivity in young infants (approximately age 5 weeks). A final sample of 33 women who provided data on preconception and prenatal stress during their pregnancy returned with their offspring for a magnetic resonance imaging scan session, which enabled us to characterize amygdala-mPFC structural and functional connectivity as a function of prenatal stress. Increased prenatal stress was associated with decreased functional connectivity and increased structural connectivity between the amygdala and mPFC. These results provide insight into the influence of prenatal maternal stress on the early development of this critical regulatory circuitry.

Psychology and neuroscience applied to financial decision-making.

All financial bubbles eventually burst and cause financial crises. In 2008 the US housing bubble burst, causing the global economy to suffer for 4 years. While the 2008 crisis received considerable attention because of its global impact, in the 21st century alone, there have been more than 10 financial crises. While economic, political and legal analysis of the crises have dominated academia, this dissertation argues that an interdisciplinary approach to financial market analysis is required to better understand why they occur. This argument is based on the idea, that the choices of traders are at the core of this issue, and consequently an understanding of trader decision-making behavior was required. Economic models of decision-making are unable to explain this behavior, as they assume decision-making to be an entirely rational process. To address this limitation, findings in neuroscience, psychology and biology are considered. Using this approach, this chapter outlines the role of different neural mechanisms, gut-feelings and hormonal states, that facilitate irrational behavior and increase a trader's susceptibility to partake in bubble markets.

A human subcortical network underlying social avoidance revealed by risky economic choices.

Social interactions have a major impact on well-being. While many individuals actively seek social situations, others avoid them, at great cost to their private and professional life. The neural mechanisms underlying individual differences in social approach or avoidance tendencies are poorly understood. Here we estimated people's subjective value of engaging in a social situation. In each trial, more or less socially anxious participants chose between an interaction with a human partner providing social feedback and a monetary amount. With increasing social anxiety, the subjective value of social engagement decreased; amygdala BOLD response during decision-making and when experiencing social feedback increased; ventral striatum BOLD response to positive social feedback decreased; and connectivity between these regions during decision-making increased. Amygdala response was negatively related to the subjective value of social engagement. These findings suggest a relation between trait social anxiety/social avoidance and activity in a subcortical network during social decision-making.

Subcortical Substrates of Explore-Exploit Decisions in Primates.

The explore-exploit dilemma refers to the challenge of deciding when to forego immediate rewards and explore new opportunities that could lead to greater rewards in the future. While motivational neural circuits facilitate learning based on past choices and outcomes, it is unclear whether they also support computations relevant for deciding when to explore. We recorded neural activity in the amygdala and ventral striatum of rhesus macaques as they solved a task that required them to balance novelty-driven exploration with exploitation of what they had already learned. Using a partially observable Markov decision process (POMDP) model to quantify explore-exploit trade-offs, we identified that the ventral striatum and amygdala differ in how they represent the immediate value of exploitative choices and the future value of exploratory choices. These findings show that subcortical motivational circuits are important in guiding explore-exploit decisions.

The neural circuitry of affect-induced distortions of trust.

Aversive affect is likely a key source of irrational human decision-making, but still, little is known about the neural circuitry underlying emotion-cognition interactions during social behavior. We induced incidental aversive affect via prolonged periods of threat of shock, while 41 healthy participants made investment decisions concerning another person or a lottery. Negative affect reduced trust, suppressed trust-specific activity in the left temporoparietal junction (TPJ), and reduced functional connectivity between the TPJ and emotion-related regions such as the amygdala. The posterior superior temporal sulcus (pSTS) seems to play a key role in mediating the impact of affect on behavior: Functional connectivity of this brain area with left TPJ was associated with trust in the absence of negative affect, but aversive affect disrupted this association between TPJ-pSTS connectivity and behavioral trust. Our findings may be useful for a better understanding of the neural circuitry of affective distortions in healthy and pathological populations.

Socioeconomic disadvantage, brain morphometry, and attentional bias to threat in middle childhood.

Socioeconomic disadvantage is associated with higher rates of psychopathology as well as hippocampus, amygdala and prefrontal cortex structure. However, little is known about how variations in brain morphometry are associated with socio-emotional risks for mood disorders in children growing up in families experiencing low income. In the current study, using structural magnetic resonance imaging, we examined the relationship between socioeconomic disadvantage and gray matter volume in the hippocampus, amygdala, and ventrolateral prefrontal cortex in a sample of children (n = 34) in middle childhood. Using an affective dot probe paradigm, we examined the association between gray matter volume in these regions and attentional bias to threat, a risk marker for mood disorders including anxiety disorders. We found that lower income-to-needs ratio was associated with lower bilateral hippocampal and right amygdala volume, but not prefrontal cortex volumes. Moreover, lower attentional bias to threat was associated with greater left hippocampal volume. We provide evidence of a relationship between income-related variations in brain structure and attentional bias to threat, a risk for mood disorders. Therefore, these findings support an environment-morphometry-behavior relationship that contributes to the understanding of income-related mental health disparities in childhood.

Amygdala reactivity as a marker of differential susceptibility to socioeconomic resources during early adulthood.

Models of differential susceptibility hypothesize that neural function may be a marker of differential susceptibility to context, but no studies have tested this hypothesis. Using a sample of 310 young men from low-income urban neighborhoods, this study investigated amygdala reactivity to facial expressions as a moderator of the relations between socioeconomic resources and later antisocial behavior (AB) and income. For individuals with high amygdala reactivity, greater socioeconomic resources at age 20 predicted less AB and greater income at age 22. For young men with low amygdala reactivity, however, socioeconomic resources at age 20 did not predict later outcomes. Amygdala reactivity to fearful facial expressions, key to the etiology of AB, moderated links between resources and AB. In contrast, amygdala reactivity more generally to multiple facial expressions moderated the effects of resources on later income attainment. Both interactions met rigorous quantitative criteria for patterns of differential susceptibility rather than diathesis stress or vantage sensitivity. Moreover, these associations remained significant after inclusion of socioeconomic resources during earlier developmental periods. These results suggest that greater amygdala reactivity to facial expressions is a marker of greater susceptibility to context, for better or for worse, during the transition to adulthood. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Neural Correlates of Giving Social Support: Differences Between Giving Targeted Versus Untargeted Support.

OBJECTIVE: Giving support contributes to the link between social ties and health; however, the neural mechanisms are not known. Giving support in humans may rely on neural regions implicated in parental care in animals. The current studies, therefore, assess the contribution of parental care-related neural regions to giving support in humans and, as a further theoretical test, examine whether the benefits of giving targeted support to single, identifiable individuals in need extend to giving untargeted support to larger societal causes. METHODS: For study 1 (n = 45, M (SD) age = 21.98 (3.29), 69% females), participants completed a giving support task, followed by an emotional faces task in the functional magnetic resonance imaging scanner. For study 2 (n = 382, M (SD) age = 43.03 (7.28), 52% females), participants self-reported on their giving support behavior and completed an emotional faces task in the functional magnetic resonance imaging scanner. RESULTS: In study 1, giving targeted (versus untargeted) support resulted in greater feelings of social connection and support effectiveness. Furthermore, greater septal area activity, a region centrally involved in parental care in animals, to giving targeted support was associated with less right amygdala activity to an emotional faces task (r = -.297, 95% confidence interval = -.547 to -.043). Study 2 replicated and extended this association to show that self-reports of giving targeted support were associated with less amygdala activity to a different emotional faces task, even when adjusting for other social factors (r = -.105, 95% confidence interval = -.200 to -.011). Giving untargeted support was not related to amygdala activity in either study. CONCLUSIONS: Results highlight the unique benefits of giving targeted support and elucidate neural pathways by which giving support may lead to health.

Adaptive spectral tracking for coherence estimation: the z-tracker.

OBJECTIVE: A major challenge in non-stationary signal analysis is reliable estimation of correlation. Neurophysiological recordings can be many minutes in duration with data that exhibits correlation which changes over different time scales. Local smoothing can be used to estimate time-dependency, however, an effective framework needs to adjust levels of smoothing in response to changes in correlation. APPROACH: Here we present a novel data-adaptive algorithm, the z-tracker, for estimating local correlation in segmented data. The algorithm constructs single segment coherence estimates using multi-taper windows. These are subject to adaptive Kalman filtering/smoothing in the z-domain to construct a local coherence estimate for each segment. The error residual for each segment determines the levels of process noise, allowing the filter to adapt rapidly to sudden changes in correlation while applying greater smoothing to data where the correlation is consistent across segments. The method is compared to wavelet coherence, calculated using orthogonal Morse wavelets. MAIN RESULTS: The performance of the z-tracker is quantified against Morse wavelet coherence using a mean square deviation (MSD) metric. The z-tracker has significantly lower MSD than the wavelet estimate for time-varying coherence over long time scales (∼10-20 s), whereas the wavelet has lower MSD for coherence varying over short time scales (∼1-2 s). The z-tracker also has a lower MSD for slowly varying coherence with occasional step changes. The method is applied to detect changes in coherence in paired LFP recordings from rat prefrontal cortex and amygdala in response to a pharmacological challenge. SIGNIFICANCE: The z-tracker provides an effective and efficient method to estimate time varying correlation in multivariate data, leading to better characterisation of neurophysiology signals where correlation is subject to slow modulation over time. A number of suggestions are included for future refinements.

Putting race in context: social class modulates processing of race in the ventromedial prefrontal cortex and amygdala.

A growing body of literature demonstrates that racial group membership can influence neural responses, e.g. when individuals perceive or interact with persons of another race. However, little attention has been paid to social class, a factor that interacts with racial inequalities in American society. We extend previous literature on race-related neural activity by focusing on how the human brain responds to racial out-groups cast in positively valued social class positions vs less valued ones. We predicted that the ventromedial prefrontal cortex (vmPFC) and the amygdala would have functionally dissociable roles, with the vmPFC playing a more significant role within socially valued in-groups (i.e. the middle-class) and the amygdala having a more crucial role for socially ambivalent and threatening categories (i.e. upper and lower class). We tested these predictions with two complementary studies: (i) a neuropsychological experiment with patients with the vmPFC or amygdala lesions, contrasted with brain damaged and normal comparison participants, and (ii) a functional magnetic resonance imaging experiment with 15 healthy adults. Our findings suggest that two distinct mechanisms underlie class-based racial evaluations, one engaging the vmPFC for positively identified in-group class and another recruiting the amygdala for the class groups that are marginalized or perceived as potential threats.

Socioeconomic disadvantage, neural responses to infant emotions, and emotional availability among first-time new mothers.

During the early postpartum period, mothers exhibit increased amygdala responses to positive infant expressions, which are important for positive mother-infant relationships. Socioeconomic disadvantage is associated with altered amygdala response to emotional stimuli as well as more negative mother-infant relationships. However, little is known about the role of socioeconomic disadvantage in neural responses specifically to infants. Thus, we examined whether socioeconomic disadvantage (indexed by lower income-to-needs ratio) is associated with neural responses to infant emotions and parenting behaviors among new mothers. Using fMRI, neural responses to infants' emotional expressions (positive, negative, and neutral faces) were assessed among 39 low- and middle-income first-time mothers during 0-6 postpartum months. Lower income-to-needs ratio was associated with dampened amygdala responses to positive infant faces, but increased amygdala responses to negative infant faces. An indirect effect of socioeconomic disadvantage on emotional availability via amygdala activation suggests that socioeconomic disadvantage is associated with heightened neural sensitivity to infants' negative emotions, which is further associated with mothers' intrusiveness observed during interactions with their own infant. The findings suggest that low-income mothers may be more vulnerable to altered neural processing of infants' emotional expressions which may further influence mothers' emotional availability during interactions with their own infants.

Neural Basis for Economic Saving Strategies in Human Amygdala-Prefrontal Reward Circuits.

Economic saving is an elaborate behavior in which the goal of a reward in the future directs planning and decision-making in the present. Here, we measured neural activity while subjects formed simple economic saving strategies to accumulate rewards and then executed their strategies through choice sequences of self-defined lengths. Before the initiation of a choice sequence, prospective activations in the amygdala predicted subjects' internal saving plans and their value up to two minutes before a saving goal was achieved. The valuation component of this planning activity persisted during execution of the saving strategy and predicted subjects' economic behavior across different tasks and testing days. Functionally coupled amygdala and prefrontal cortex activities encoded distinct planning components that signaled the transition from saving strategy formation to execution and reflected individual differences in saving behavior. Our findings identify candidate neural mechanisms for economic saving in amygdala and prefrontal cortex and suggest a novel planning function for the human amygdala in directing strategic behavior toward self-determined future rewards.

Primate amygdala neurons evaluate the progress of self-defined economic choice sequences.

The amygdala is a prime valuation structure yet its functions in advanced behaviors are poorly understood. We tested whether individual amygdala neurons encode a critical requirement for goal-directed behavior: the evaluation of progress during sequential choices. As monkeys progressed through choice sequences toward rewards, amygdala neurons showed phasic, gradually increasing responses over successive choice steps. These responses occurred in the absence of external progress cues or motor preplanning. They were often specific to self-defined sequences, typically disappearing during instructed control sequences with similar reward expectation. Their build-up rate reflected prospectively the forthcoming choice sequence, suggesting adaptation to an internal plan. Population decoding demonstrated a high-accuracy progress code. These findings indicate that amygdala neurons evaluate the progress of planned, self-defined behavioral sequences. Such progress signals seem essential for aligning stepwise choices with internal plans. Their presence in amygdala neurons may inform understanding of human conditions with amygdala dysfunction and deregulated reward pursuit.

Major neurotransmitter systems in dorsal hippocampus and basolateral amygdala control social recognition memory.

Social recognition memory (SRM) is crucial for reproduction, forming social groups, and species survival. Despite its importance, SRM is still relatively little studied. Here we examine the participation of the CA1 region of the dorsal hippocampus (CA1) and the basolateral amygdala (BLA) and that of dopaminergic, noradrenergic, and histaminergic systems in both structures in the consolidation of SRM. Male Wistar rats received intra-CA1 or intra-BLA infusions of different drugs immediately after the sample phase of a social discrimination task and 24-h later were subjected to a 5-min retention test. Animals treated with the protein synthesis inhibitor, anisomycin, into either the CA1 or BLA were unable to recognize the previously exposed juvenile (familiar) during the retention test. When infused into the CA1, the ß-adrenoreceptor agonist, isoproterenol, the D1/D5 dopaminergic receptor antagonist, SCH23390, and the H2 histaminergic receptor antagonist, ranitidine, also hindered the recognition of the familiar juvenile 24-h later. The latter drug effects were more intense in the CA1 than in the BLA. When infused into the BLA, the ß-adrenoreceptor antagonist, timolol, the D1/D5 dopamine receptor agonist, SKF38393, and the H2 histaminergic receptor agonist, ranitidine, also hindered recognition of the familiar juvenile 24-h later. In all cases, the impairment to recognize the familiar juvenile was abolished by the coinfusion of agonist plus antagonist. Clearly, both the CA1 and BLA, probably in that order, play major roles in the consolidation of SRM, but these roles are different in each structure vis-à-vis the involvement of the ß-noradrenergic, D1/D5-dopaminergic, and H2-histaminergic receptors therein.

Reproducibility assessment of brain responses to visual food stimuli in adults with overweight and obesity.

OBJECTIVE: The brain's reward system influences ingestive behavior and subsequently obesity risk. Functional magnetic resonance imaging (fMRI) is a common method for investigating brain reward function. This study sought to assess the reproducibility of fasting-state brain responses to visual food stimuli using BOLD fMRI. METHODS: A priori brain regions of interest included bilateral insula, amygdala, orbitofrontal cortex, caudate, and putamen. Fasting-state fMRI and appetite assessments were completed by 28 women (n = 16) and men (n = 12) with overweight or obesity on 2 days. Reproducibility was assessed by comparing mean fasting-state brain responses and measuring test-retest reliability of these responses on the two testing days. RESULTS: Mean fasting-state brain responses on day 2 were reduced compared with day 1 in the left insula and right amygdala, but mean day 1 and day 2 responses were not different in the other regions of interest. With the exception of the left orbitofrontal cortex response (fair reliability), test-retest reliabilities of brain responses were poor or unreliable. CONCLUSIONS: fMRI-measured responses to visual food cues in adults with overweight or obesity show relatively good mean-level reproducibility but considerable within-subject variability. Poor test-retest reliability reduces the likelihood of observing true correlations and increases the necessary sample sizes for studies.