Continuity in the neural system supporting children's theory of mind development: Longitudinal links between task-independent EEG and task-dependent fMRI.

Children's explicit theory of mind (ToM) understandings change over early childhood. We examined whether there is longitudinal stability in the neurobiological bases of ToM across this time period. A previous study found that source-localized resting EEG alpha attributable to the dorsal medial prefrontal cortex (DMPFC) and right temporoparietal junction (RTPJ) was associated with children's performance on a battery of theory of mind tasks. Here, we investigated a small subset of children (N = 12) in that original study as a preliminary investigation of whether behavioral measures of ToM performance, and/or EEG localized to the DMPFC or RTPJ predicted ToM-specific fMRI responses 3.5 years later. Results showed that preschoolers' behavioral ToM-performance positively predicted later ToM-specific fMRI responses in the DMPFC. Preschoolers' resting EEG attributable to the DMPFC also predicted later ToM-specific fMRI responses in the DMPFC. Given the small sample, results represent a first exploration and require replication. Intriguingly, they suggest that early maturation of the area of the DMPFC related to ToM reasoning is positively linked with its specific recruitment for ToM reasoning later in development, affording implications for characterizing conceptual ToM development, and its underlying neural supports

Anhedonia and depression severity dissociated by dmPFC resting-state functional connectivity in adolescents

Introduction: Given the heterogeneity within depression, in this study we aim to examine how RSFC in adolescents is related to anhedonia and depression severity on a continuum in line with the RDoC approach. Methods: We examined how RSFC in the dorsal medial prefrontal cortex (dmPFC), nucleus accumbens (NAcc) and pregenual anterior cingulate cortex (pgACC) was related to anhedonia and depression severity in eighty six adolescents (13-21 yrs.). Results: We found both anhedonia and depression severity related to decreased dmPFC RSFC with the precuneus, a part of the default mode network. However we also found that increased dmPFC connectivity with the ACC/paracingulate gyrus related to anhedonia whereas increased RSFC with the frontal pole related to depression severity. Discussion: This work extends the view that the dmPFC is a potential therapeutic target for depression in two ways. 1. We report dmPFC connectivity in adolescents and 2. We show different dmPFC RSFC specific to anhedonia and depression severity, providing neural targets for intervention in young people at risk of depression

Rule learning enhances structural plasticity of long-range axons in frontal cortex.

Rules encompass cue-action-outcome associations used to guide decisions and strategies in a specific context. Subregions of the frontal cortex including the orbitofrontal cortex (OFC) and dorsomedial prefrontal cortex (dmPFC) are implicated in rule learning, although changes in structural connectivity underlying rule learning are poorly understood. We imaged OFC axonal projections to dmPFC during training in a multiple choice foraging task and used a reinforcement learning model to quantify explore-exploit strategy use and prediction error magnitude. Here we show that rule training, but not experience of reward alone, enhances OFC bouton plasticity. Baseline bouton density and gains during training correlate with rule exploitation, while bouton loss correlates with exploration and scales with the magnitude of experienced prediction errors. We conclude that rule learning sculpts frontal cortex interconnectivity and adjusts a thermostat for the explore-exploit balance

Long-range orbitofrontal and amygdala axons show divergent patterns of maturation in the frontal cortex across adolescence.

The adolescent transition from juvenile to adult is marked by anatomical and functional remodeling of brain networks. Currently, the cellular and synaptic level changes underlying the adolescent transition are only coarsely understood. Here, we use two-photon imaging to make time-lapse observations of long-range axons that innervate the frontal cortex in the living brain. We labeled cells in the orbitofrontal cortex (OFC) and basolateral amygdala (BLA) and imaged their axonal afferents to the dorsomedial prefrontal cortex (dmPFC). We also imaged the apical dendrites of dmPFC pyramidal neurons. Images were taken daily in separate cohorts of juvenile (P24-P28) and young adult mice (P64-P68), ages where we have previously discovered differences in dmPFC dependent decision-making. Dendritic spines were pruned across this peri-adolescent period, while BLA and OFC afferents followed alternate developmental trajectories. OFC boutons showed no decrease in density, but did show a decrease in daily bouton gain and loss with age. BLA axons showed an increase in both bouton density and daily bouton gain at the later age, suggesting a delayed window of enhanced plasticity. Our findings reveal projection specific maturation of synaptic structures within a single frontal region and suggest that stabilization is a more general characteristic of maturation than pruning

Extinction of cue-evoked food seeking recruits a GABAergic interneuron ensemble in the dorsal medial prefrontal cortex of mice

Animals must quickly adapt food-seeking strategies to locate nutrient sources in dynamically changing environments. Learned associations between food and environmental cues that predict its availability promote food-seeking behaviors. However, when such cues cease to predict food availability, animals undergo 'extinction' learning, resulting in the inhibition of food-seeking responses. Repeatedly activated sets of neurons, or 'neuronal ensembles', in the dorsal medial prefrontal cortex (dmPFC) are recruited following appetitive conditioning and undergo physiological adaptations thought to encode cue-reward associations. However, little is known about how the recruitment and intrinsic excitability of such dmPFC ensembles are modulated by extinction learning. Here, we used in vivo 2-Photon imaging in male Fos-GFP mice that express green fluorescent protein (GFP) in recently behaviorally-activated neurons to determine the recruitment of activated pyramidal and GABAergic interneuron mPFC ensembles during extinction. During extinction, we revealed a persistent activation of a subset of interneurons which emerged from a wider population of interneurons activated during the initial extinction session. This activation pattern was not observed in pyramidal cells, and extinction learning did not modulate the excitability properties of activated neurons. Moreover, extinction learning reduced the likelihood of reactivation of pyramidal cells activated during the initial extinction session. Our findings illuminate novel neuronal activation patterns in the dmPFC underlying extinction of food-seeking, and in particular, highlight an important role for interneuron ensembles in this inhibitory form of learning

The role of automaticity and attention in neural processes underlying empathy for happiness, sadness, and anxiety.

Although many studies have examined the neural basis of empathy, relatively little is known about how empathic processes are affected by different attentional conditions. Thus, we examined whether instructions to empathize might amplify responses in empathy-related regions and whether cognitive load would diminish the involvement of these regions. Thirty-two participants completed a functional magnetic resonance imaging session assessing empathic responses to individuals experiencing happy, sad, and anxious events. Stimuli were presented under three conditions: watching naturally, actively empathizing, and under cognitive load. Across analyses, we found evidence for a core set of neural regions that support empathic processes (dorsomedial prefrontal cortex, DMPFC; medial prefrontal cortex, MPFC; temporoparietal junction, TPJ; amygdala; ventral anterior insula, AI; and septal area, SA). Two key regions-the ventral AI and SA-were consistently active across all attentional conditions, suggesting that they are automatically engaged during empathy. In addition, watching vs. empathizing with targets was not markedly different and instead led to similar subjective and neural responses to others' emotional experiences. In contrast, cognitive load reduced the subjective experience of empathy and diminished neural responses in several regions related to empathy and social cognition (DMPFC, MPFC, TPJ, and amygdala). The results reveal how attention impacts empathic processes and provides insight into how empathy may unfold in everyday interactions

Outcome contingency selectively affects the neural coding of outcomes but not of tasks

Value-based decision-making is ubiquitous in every-day life, and critically depends on the contingency between choices and their outcomes. Only if outcomes are contingent on our choices can we make meaningful value-based decisions. Here, we investigate the effect of outcome contingency on the neural coding of rewards and tasks. Participants performed a reversal-learning paradigm in which reward outcomes were contingent on trial-by-trial choices, and performed a ‘free choice’ paradigm in which rewards were random and not contingent on choices. We hypothesized that contingent outcomes enhance the neural coding of rewards and tasks, which was tested using multivariate pattern analysis of fMRI data. Reward outcomes were encoded in a large network including the striatum, dmPFC and parietal cortex, and these representations were indeed amplified for contingent rewards. Tasks were encoded in the dmPFC at the time of decision-making, and in parietal cortex in a subsequent maintenance phase. We found no evidence for contingency-dependent modulations of task signals, demonstrating highly similar coding across contingency conditions. Our findings suggest selective effects of contingency on reward coding only, and further highlight the role of dmPFC and parietal cortex in value-based decision-making, as these were the only regions strongly involved in both reward and task coding

Capacity and tendency: A neuroscientific framework for the study of emotion regulation.

It is widely accepted that the ability to effectively regulate one's emotions is a cornerstone of physical and mental health. As such, it should come as no surprise that the number of neuroimaging studies focused on emotion regulation and associated processes has increased exponentially in the past decade. To date, neuroimaging research on this topic has examined two distinct but complementary features of emotion regulation - the capacity to effectively utilize a strategy to regulate emotion and to a lesser extent, the tendency to choose to regulate. However, theoretical accounts of emotion regulation have only recently begun to distinguish capacity from tendency. In the present review, we provide a novel framework for conceptualizing these two intertwined, yet distinct, facets of emotion regulation. First we characterize brain regions that support emotion generation and are thus targeted by emotion regulation. Next, we synthesize findings from the dozens of neuroimaging studies that have examined emotion regulation capacity, focusing in particular on the most commonly studied emotion regulation strategy - reappraisal. Finally, we discuss emerging neuroimaging research examining state and trait regulatory tendencies. We conclude by integrating findings from neuroimaging research on emotion regulation capacity and tendency and suggest ways that this integrated model can inform basic and translational neuroscientific research on emotion regulation

Neuronal bases of structural coherence in contemporary dance observation

The neuronal processes underlying dance observation have been the focus of an increasing number of brain imaging studies over the past decade. However, the existing literature mainly dealt with effects of motor and visual expertise, whereas the neural and cognitive mechanisms that underlie the interpretation of dance choreographies remained unexplored. Hence, much attention has been given to the Action Observation Network (AON) whereas the role of other potentially relevant neuro-cognitive mechanisms such as mentalizing (theory of mind) or language (narrative comprehension) in dance understanding is yet to be elucidated. We report the results of an fMRI study where the structural coherence of short contemporary dance choreographies was manipulated parametrically using the same taped movement material. Our participants were all trained dancers. The whole-brain analysis argues that the interpretation of structurally coherent dance phrases involves a subpart (Superior Parietal) of the AON as well as mentalizing regions in the dorsomedial Prefrontal Cortex. An ROI analysis based on a similar study using linguistic materials (Pallier et al. 2011) suggests that structural processing in language and dance might share certain neural mechanisms