Selective modulation of interhemispheric connectivity by transcranial alternating current stimulation influences binaural integration.

Brain connectivity plays a major role in the encoding, transfer, and integration of sensory information. Interregional synchronization of neural oscillations in the γ-frequency band has been suggested as a key mechanism underlying perceptual integration. In a recent study, we found evidence for this hypothesis showing that the modulation of interhemispheric oscillatory synchrony by means of bihemispheric high-density transcranial alternating current stimulation (HD-TACS) affects binaural integration of dichotic acoustic features. Here, we aimed to establish a direct link between oscillatory synchrony, effective brain connectivity, and binaural integration. We experimentally manipulated oscillatory synchrony (using bihemispheric γ-TACS with different interhemispheric phase lags) and assessed the effect on effective brain connectivity and binaural integration (as measured with functional MRI and a dichotic listening task, respectively). We found that TACS reduced intrahemispheric connectivity within the auditory cortices and antiphase (interhemispheric phase lag 180°) TACS modulated connectivity between the two auditory cortices. Importantly, the changes in intra- and interhemispheric connectivity induced by TACS were correlated with changes in perceptual integration. Our results indicate that γ-band synchronization between the two auditory cortices plays a functional role in binaural integration, supporting the proposed role of interregional oscillatory synchrony in perceptual integration.

Perceptual control or action-selection? Comment on: a perceptual control theory of emotional action.

The Perceptual Control Theory of Emotional Action provides a compelling view of the synergy between action and perception in the context of emotion. In this invited response, we outline three suggestions to further clarify and concretesise the theory in the hope that it can provide a solid basis for the theoretical, empirical, and clinical fields of emotion and emotion regulation. First, we emphasise the importance of concretesising these ideas in a way that is biologically plausible and testable in terms of its neuronal implementation, which has not been addressed in the main manuscript. Secondly, we highlight the challenges for this account to effectively describe core symptoms in emotional disorders, an essential step if the theory aims to foster the development of better-tuned neurocognitively grounded interventions. Finally, we take a leap on what action-oriented accounts of emotion can mean for the field of emotion regulation.

Human Lateral Frontal Pole Contributes to Control over Emotional Approach-Avoidance Actions.

Regulation of emotional behavior is essential for human social interactions. Recent work has exposed its cognitive complexity, as well as its unexpected reliance on portions of the anterior PFC (aPFC) also involved in exploration, relational reasoning, and counterfactual choice, rather than on dorsolateral and medial prefrontal areas involved in several forms of cognitive control. This study anatomically qualifies the contribution of aPFC territories to the regulation of prepotent approach-avoidance action tendencies elicited by emotional faces, and explores a possible structural pathway through which this emotional action regulation might be implemented. We provide converging evidence from task-based fMRI, diffusion-weighted imaging, and functional connectivity fingerprints for a novel neural element in emotional regulation. Task-based fMRI in human male participants (N = 40) performing an emotional approach-avoidance task identified aPFC territories involved in the regulation of action tendencies elicited by emotional faces. Connectivity fingerprints, based on diffusion-weighted imaging and resting-state connectivity, localized those task-defined frontal regions to the lateral frontal pole (FPl), an anatomically defined portion of the aPFC that lacks a homologous counterpart in macaque brains. Probabilistic tractography indicated that 10%-20% of interindividual variation in emotional regulation abilities is accounted for by the strength of structural connectivity between FPl and amygdala. Evidence from an independent replication sample (N = 50; 10 females) further substantiated this result. These findings provide novel neuroanatomical evidence for incorporating FPl in models of control over human action tendencies elicited by emotional faces.SIGNIFICANCE STATEMENT Successful regulation of emotional behaviors is a prerequisite for successful participation in human society, as is evidenced by the social isolation and loss of occupational opportunities often encountered by people suffering from emotion regulation disorders, such as social-anxiety disorder and psychopathy. Knowledge about the precise cortical regions and connections supporting this control is crucial for understanding both the nature of computations needed to successfully traverse the space of possible actions in social situations, and the potential interventions that might result in efficient treatment of social-emotional disorders. This study provides evidence for a precise cortical region (lateral frontal pole) and a structural pathway (the ventral amygdalofugal bundle) through which a cognitively complex form of emotional action regulation might be implemented in the human brain.

Cortical Oscillatory Mechanisms Supporting the Control of Human Social-Emotional Actions.

The human anterior prefrontal cortex (aPFC) is involved in regulating social-emotional behavior, presumably by modulating effective connectivity with downstream parietal, limbic, and motor cortices. Regulating that connectivity might rely on theta-band oscillations (4-8 Hz), a brain rhythm known to create overlapping periods of excitability between distant regions by temporally releasing neurons from inhibition. Here, we used MEG to understand how aPFC theta-band oscillations implement control over prepotent social-emotional behaviors; that is, the control over automatically elicited approach and avoidance actions. Forty human male participants performed a social approach-avoidance task in which they approached or avoided visually displayed emotional faces (happy or angry) by pulling or pushing a joystick. Approaching angry and avoiding happy faces (incongruent condition) requires rapid application of cognitive control to override prepotent habitual action tendencies to approach appetitive and to avoid aversive situations. In the time window before response delivery, trial-by-trial variations in aPFC theta-band power (6 Hz) predicted reaction time increases during emotional control and were inversely related to beta-band power (14-22 Hz) over parietofrontal cortex. In sensorimotor areas contralateral to the moving hand, premovement gamma-band rhythms (60-90 Hz) were stronger during incongruent than congruent trials, with power increases phase locked to peaks of the aPFC theta-band oscillations. These findings define a mechanistic relation between cortical areas involved in implementing rapid control over human social-emotional behavior. The aPFC may bias neural processing toward rule-driven actions and away from automatic emotional tendencies by coordinating tonic disinhibition and phasic enhancement of parietofrontal circuits involved in action selection.SIGNIFICANCE STATEMENT Being able to control social-emotional behavior is crucial for successful participation in society, as is illustrated by the severe social and occupational difficulties experienced by people suffering from social motivational disorders such as social anxiety. In this study, we show that theta-band oscillations in the anterior prefrontal cortex (aPFC), which are thought to provide temporal organization for neural firing during communication between distant brain areas, facilitate this control by linking aPFC to parietofrontal beta-band and sensorimotor gamma-band oscillations involved in action selection. These results contribute to a mechanistic understanding of cognitive control over automatic social-emotional action and point to frontal theta-band oscillations as a possible target of rhythmic neurostimulation techniques during treatment for social anxiety.

A neurocognitive theory of flexible emotion control: The role of the lateral frontal pole in emotion regulation.

Emotion regulation is essential to survive in a world full of challenges with rapidly changing contextual demands. The ability to flexibly shift between different emotional control strategies is critical to successfully deal with these demands. Recently, decision neuroscience has shown the importance of monitoring alternative control strategies. However, this insight has not been incorporated into current neurocognitive models of emotional control. Here, we integrate insights from decision and affective sciences into a novel viewpoint on emotion control, the Flexible Emotion Control Theory (FECT). This theory explains how an individual can flexibly change emotion-regulatory behavior to adapt to varying goals and contextual demands. Crucially, FECT proposes that rapid switching between alternative emotional control strategies requires concurrent evaluation of current as well as alternative (unchosen) options. The neural implementation of FECT relies on the involvement of distinct prefrontal structures, including the lateral frontal pole (FPl) and its connections with other cortical (prefrontal, parietal, motor) and subcortical systems. This novel account of emotion control integrates insights from decision sciences, clinical research, as well as meta-analytic evidence for the consistent FPl involvement during emotional control when monitoring of alternative emotional control strategies is required. Moreover, it provides novel, neurocognitively grounded starting points for interventions to improve emotion control in affective disorders, such as anxiety and aggression.

Emotion regulation from an action-control perspective.

Despite increasing interest in emotional processes in cognitive science, theories on emotion regulation have remained rather isolated, predominantly focused on cognitive regulation strategies such as reappraisal. However, recent neurocognitive evidence suggests that early emotion regulation may involve sensorimotor control in addition to other emotion-regulation processes. We propose an action-oriented view of emotion regulation, in which feedforward predictions develop from action-selection mechanisms. Those can account for acute emotional-action control as well as more abstract instances of emotion regulation such as cognitive reappraisal. We argue the latter occurs in absence of overt motor output, yet in the presence of full-blown autonomic, visceral, and subjective changes. This provides an integrated framework with testable neuro-computational predictions and concrete starting points for intervention to improve emotion control in affective disorders.

Anxious individuals shift emotion control from lateral frontal pole to dorsolateral prefrontal cortex.

Anxious individuals consistently fail in controlling emotional behavior, leading to excessive avoidance, a trait that prevents learning through exposure. Although the origin of this failure is unclear, one candidate system involves control of emotional actions, coordinated through lateral frontopolar cortex (FPl) via amygdala and sensorimotor connections. Using structural, functional, and neurochemical evidence, we show how FPl-based emotional action control fails in highly-anxious individuals. Their FPl is overexcitable, as indexed by GABA/glutamate ratio at rest, and receives stronger amygdalofugal projections than non-anxious male participants. Yet, high-anxious individuals fail to recruit FPl during emotional action control, relying instead on dorsolateral and medial prefrontal areas. This functional anatomical shift is proportional to FPl excitability and amygdalofugal projections strength. The findings characterize circuit-level vulnerabilities in anxious individuals, showing that even mild emotional challenges can saturate FPl neural range, leading to a neural bottleneck in the control of emotional action tendencies.

Studying additive effects of combining rTMS with cognitive control training: a pilot investigation.

Background: Repetitive transcranial magnetic stimulation (rTMS) on the dorsolateral prefrontal cortex (DLPFC) is an effective treatment for depression that has been proposed to work via the enhancement of cognitive control. Cognitive control training (CCT) can also alleviate depression by relying on DLPFC activation. As the additive effects of rTMS and CCT are unclear, we set out to conduct a within-subject pilot study in healthy controls. Methods: Seventeen participants received two sessions of individualized resting-state connectivity-guided high-frequency rTMS, while randomly performing CCT or a control task. After each session, a negative mood was induced. Results: We found effects on mood and cognitive control after rTMS + CCT as well as rTMS + control, which were indiscriminative between conditions. Based on the statistical evidence for the absence of an additive effect of CCT, we did not perform a full study. Conclusion: Our results demonstrate no differential effects of single sessions combining rTMS and CCT in a healthy population, even with the methodological improvement of individualized neuronavigation. The improvement in cognitive control seen in both conditions could indicate that a simple cognitive task is sufficient when studying additive rTMS effects. Future studies should focus on augmenting the effects of various cognitive tasks and compare the present interventions with rTMS or cognitive tasks alone.

Approach-Avoidance Decisions Under Threat: The Role of Autonomic Psychophysiological States.

Acutely challenging or threatening situations frequently require approach-avoidance decisions. Acute threat triggers fast autonomic changes that prepare the body to freeze, fight or flee. However, such autonomic changes may also influence subsequent instrumental approach-avoidance decisions. Since defensive bodily states are often not considered in value-based decision-making models, it remains unclear how they influence the decision-making process. Here, we aim to bridge this gap by discussing the existing literature on the potential role of threat-induced bodily states on decision making and provide a new neurocomputational framework explaining how these effects can facilitate or bias approach-avoid decisions under threat. Theoretical accounts have stated that threat-induced parasympathetic activity is involved in information gathering and decision making. Parasympathetic dominance over sympathetic activity is particularly seen during threat-anticipatory freezing, an evolutionarily conserved response to threat demonstrated across species and characterized by immobility and bradycardia. Although this state of freezing has been linked to altered information processing and action preparation, a full theoretical treatment of the interactions with value-based decision making has not yet been achieved. Our neural framework, which we term the Threat State/Value Integration (TSI) Model, will illustrate how threat-induced bodily states may impact valuation of competing incentives at three stages of the decision-making process, namely at threat evaluation, integration of rewards and threats, and action initiation. Additionally, because altered parasympathetic activity and decision biases have been shown in anxious populations, we will end with discussing how biases in this system can lead to characteristic patterns of avoidance seen in anxiety-related disorders, motivating future pre-clinical and clinical research.

Improving emotional-action control by targeting long-range phase-amplitude neuronal coupling.

Control over emotional action tendencies is essential for everyday interactions. This cognitive function fails occasionally during socially challenging situations, and systematically in social psychopathologies. We delivered dual-site phase-coupled brain stimulation to facilitate theta-gamma phase-amplitude coupling between frontal regions known to implement that form of control, while neuropsychologically healthy human male participants were challenged to control their automatic action tendencies in a social-emotional approach/avoidance-task. Participants had increased control over their emotional action tendencies, depending on the relative phase and dose of the intervention. Concurrently measured fMRI effects of task and stimulation indicated that the intervention improved control by increasing the efficacy of anterior prefrontal inhibition over the sensorimotor cortex. This enhancement of emotional action control provides causal evidence for phase-amplitude coupling mechanisms guiding action selection during emotional-action control. Generally, the finding illustrates the potential of physiologically-grounded interventions aimed at reducing neural noise in cerebral circuits where communication relies on phase-amplitude coupling.

Lateral frontal pole and relational processing: Activation patterns and connectivity profile.

The functional contribution of the lateral frontal cortex to behavior has been discussed with reference to several higher-order cognitive domains. In a separate line of research, recent studies have focused on the anatomical organization of this part of the brain. These different approaches are rarely combined. Here, we combine previous work using anatomical connectivity that identified a lateral subdivision of the human frontal pole and work that suggested a general role for rostrolateral prefrontal cortex in processing higher-order relations, irrespective of the type of information. We asked healthy human volunteers to judge the relationship between pairs of stimuli, a task previously suggested to engage the lateral frontal pole. Presenting both shape and face stimuli, we indeed observed overlapping activation of the lateral prefrontal cortex when subjects judged relations between pairs. Using resting state functional MRI, we confirmed that the activated region's whole-brain connectivity most strongly resembles that of the lateral frontal pole. Using diffusion MRI, we showed that the pattern of connections of this region with the main association fibers again is most similar to that of the lateral frontal pole, consistent with the observation that it is this anatomical region that is involved in relational processing.