Effects of Experiencing CS-US Pairings on Instructed Fear Reversal.

Fear learning allows us to identify and anticipate aversive events and adapt our behavior accordingly. This is often thought to rely on associative learning mechanisms where an initially neutral conditioned stimulus (CS) is repeatedly paired with an aversive unconditioned stimulus (US), eventually leading to the CS also being perceived as aversive and threatening. Importantly, however, humans also show verbal fear learning. Namely, they have the ability to change their responses to stimuli rapidly through verbal instructions about CS-US pairings. Past research on the link between experience-based and verbal fear learning indicated that verbal instructions about a reversal of CS-US pairings can fully override the effects of previously experienced CS-US pairings, as measured through fear ratings, skin conductance, and fear-potentiated startle. However, it remains an open question whether such instructions can also annul learned CS representations in the brain. Here, we used a fear reversal paradigm (female and male participants) in conjunction with representational similarity analysis of fMRI data to test whether verbal instructions fully override the effects of experienced CS-US pairings in fear-related brain regions or not. Previous research suggests that only the right amygdala should show lingering representations of previously experienced threat ("pavlovian trace"). Unexpectedly, we found evidence for the residual effect of prior CS-US experience to be much more widespread than anticipated, in the amygdala but also cortical regions like the dorsal anterior cingulate or dorsolateral prefrontal cortex. This finding shines a new light on the interaction of different fear learning mechanisms, at times with unexpected consequences.SIGNIFICANCE STATEMENT Humans are able to learn about aversive stimuli both from experience (i.e., repeated pairings of conditioned stimulus (CS) and unconditioned stimulus (US; pavlovian conditioning), and from verbal instructions about stimulus pairings. Understanding how experience-based and verbal learning processes interact is key for understanding the cognitive and neural underpinnings of fear learning. We tested whether prior aversive experiences (CS-US pairings) affected subsequent verbal learning, searching for lingering threat signals after verbal instructions reversed a CS from being threatening to being safe. While past research suggested such threat signals can only be found in the amygdala, we found evidence to be much more widespread, including the medial and lateral PFC. This highlights how experience-based and verbal learning processes interact to support adaptive behavior.

Flotillin-2 regulates epidermal growth factor receptor activation, degradation by Cbl-mediated ubiquitination, and cancer growth.

Epidermal growth factor receptor (EGFR) signaling is frequently dysregulated in various cancers. The ubiquitin ligase Casitas B-lineage lymphoma proto-oncogene (Cbl) regulates degradation of activated EGFR through ubiquitination and acts as an adaptor to recruit proteins required for trafficking. Here, we used stable isotope labeling with amino acids in cell culture mass spectrometry to compare Cbl complexes with or without epidermal growth factor (EGF) stimulation. We identified over a hundred novel Cbl interactors, and a secondary siRNA screen found that knockdown of Flotillin-2 (FLOT2) led to increased phosphorylation and degradation of EGFR upon EGF stimulation in HeLa cells. In PC9 and H441 cells, FLOT2 knockdown increased EGF-stimulated EGFR phosphorylation, ubiquitination, and downstream signaling, reversible by EGFR inhibitor erlotinib. CRISPR knockout (KO) of FLOT2 in HeLa cells confirmed EGFR downregulation, increased signaling, and increased dimerization and endosomal trafficking. Furthermore, we determined that FLOT2 interacted with both Cbl and EGFR. EGFR downregulation upon FLOT2 loss was Cbl dependent, as coknockdown of Cbl and Cbl-b restored EGFR levels. In addition, FLOT2 overexpression decreased EGFR signaling and growth. Overexpression of wildtype (WT) FLOT2, but not the soluble G2A FLOT2 mutant, inhibited EGFR phosphorylation upon EGF stimulation in HEK293T cells. FLOT2 loss induced EGFR-dependent proliferation and anchorage-independent growth. Lastly, FLOT2 KO increased tumor formation and tumor volume in nude mice and NSG mice, respectively. Together, these data demonstrated that FLOT2 negatively regulated EGFR activation and dimerization, as well as its subsequent ubiquitination, endosomal trafficking, and degradation, leading to reduced proliferation in vitro and in vivo.

The Representations of Chinese Characters: Evidence from Sublexical Components.

Little research has been done about the neural substrate of the sublexical level of Chinese word recognition. In particular, it is unclear how radicals participate in Chinese word processing. We compared two measures of radical combinability, position-general radical combinability (GRC) and position-specific radical combinability (SRC) depending on whether the position of the radical is taken into account. We selected characters with embedded target radicals that had different GRC and SRC measures. These measures were used as predictors in a parametric modulation analysis and a multivariate representational similarity analysis. Human participants with native Mandarin speakers (17 males and 24 females) were asked to read words in search of animal words. Results showed that SRC is a better predictor than GRC in decoding the neural patterns. Whole-brain analysis indicated that SRC is encoded bilaterally in the inferior frontal gyrus (IFG, pars opercularis, and pars triangularis), the middle frontal gyrus (MFG), and a region on the border of the superior parietal lobule and the inferior parietal lobule (SPL/IPL). Region-of-interest-based RSA confirmed the results of the whole-brain analysis. Furthermore, we observed a correlation of another sublexical variable, logographeme composition, with bilateral activity in SPL. Logographemes refer to the basic stroke combinations that form radicals and characters. Finally, we observed involvement of bilateral cerebellum activity in Chinese word recognition. Our findings confirm the importance of sublexical components (SRC and logographeme composition) in Chinese word recognition and also confirm that Chinese word recognition involves more bilateral processing than word recognition in alphabetical languages.SIGNIFICANCE STATEMENT Chinese is a logographic language. However, characters contain informative subword components (radicals, logographemes, and strokes). We investigated whether the position of the radical is important. We presented carefully selected words and looked where brain activity correlated with subword information. Results indicate that position-dependent radicals predict brain encoding in a network of regions associated with Chinese word recognition, including higher order regions such as bilateral IFG, MFG, and SPL/IPL. Logographeme composition had an effect as well. Our findings provide strong evidence (1) for the importance of position-specific radical information and logographemes in Chinese word recognition, (2) that current brain imaging techniques are best suited to study these, and (3) that confirms the interactive nature of Chinese character recognition.

Adaptive coding of stimulus information in human frontoparietal cortex during visual classification.

The neural mechanisms of how frontal and parietal brain regions support flexible adaptation of behavior remain poorly understood. Here, we used functional magnetic resonance imaging (fMRI) and representational similarity analysis (RSA) to investigate frontoparietal representations of stimulus information during visual classification under varying task demands. Based on prior research, we predicted that increasing perceptual task difficulty should lead to adaptive changes in stimulus coding: task-relevant category information should be stronger, while task-irrelevant exemplar-level stimulus information should become weaker, reflecting a focus on the behaviorally relevant category information. Counter to our expectations, however, we found no evidence for adaptive changes in category coding. We did find weakened coding at the exemplar-level within categories however, demonstrating that task-irrelevant information is de-emphasized in frontoparietal cortex. These findings reveal adaptive coding of stimulus information at the exemplar-level, highlighting how frontoparietal regions might support behavior even under challenging conditions.

The impact of free will beliefs on implicit learning.

A growing number of studies demonstrate that belief in free will (FWB) is dynamic, and can be reduced experimentally. Most of these studies assume that doing so has beneficial effects on behavior, as FWBs are thought to subdue unwanted automatic processes (e.g. racial stereotypes). However, relying on automatic processes can sometimes be advantageous, for instance during implicit learning (e.g. detecting and exploiting statistical regularities in the environment). In this registered report, we tested whether experimentally reducing FWBs positively affected implicit motor learning. We hypothesized that reducing FWBs would lead to both faster and stronger implicit learning, as measured using the alternating serial reaction time (ASRT) task. While we did show a manipulation effect on free will beliefs, there was no detectable effect on implicit learning processes. This finding adds to the growing body of evidence that free will belief manipulations do not meaningfully affect downstream behavior.

Manipulating Belief in Free Will and Its Downstream Consequences: A Meta-Analysis.

Ever since some scientists and popular media put forward the idea that free will is an illusion, the question has risen what would happen if people stopped believing in free will. Psychological research has investigated this question by testing the consequences of experimentally weakening people's free will beliefs. The results of these investigations have been mixed, with successful experiments and unsuccessful replications. This raises two fundamental questions: Can free will beliefs be manipulated, and do such manipulations have downstream consequences? In a meta-analysis including 145 experiments (95 unpublished), we show that exposing individuals to anti-free will manipulations decreases belief in free will and increases belief in determinism. However, we could not find evidence for downstream consequences. Our findings have important theoretical implications for research on free will beliefs and contribute to the discussion of whether reducing people's belief in free will has societal consequences.

Manipulating free will beliefs using online video games.

Research in social psychology and experimental philosophy has investigated lay people's free will beliefs (FWB). Using different approaches (i.e. experimental manipulations and vignette studies), they investigated how FWB relate to other concepts, and whether changing FWB has an impact on downstream processes such as social behavior. However, both approaches have shortcomings. While experimental manipulations used in social psychology suffer from demand effects, vignettes used in experimental philosophy are often highly abstract. Across two pre-registered studies, we developed a new approach by merging them in an online video game setting. Using this novel, experience-based FWB manipulation, we found that decreasing FWB impacted variables such as perceived control and responsibility in both studies. While the experience-based manipulation influenced participants' beliefs in free will within the context of the experience ("Within the context of the scenario, would the agent believe in free will?") in the first study, this manipulation effect did not transfer to participants' general FWB ("Do you believe in free will?") in the second study. Overall, our findings suggest a way forward in studying laypeople's beliefs in free will.

Shared Neural Representations of Cognitive Conflict and Negative Affect in the Medial Frontal Cortex.

Influential theories of Medial Frontal Cortex (MFC) function suggest that the MFC registers cognitive conflict as an aversive signal, but no study directly tested this idea. Instead, recent studies suggested that nonoverlapping regions in the MFC process conflict and affect. In this preregistered human fMRI study (male and female), we used MVPAs to identify which regions respond similarly to conflict and aversive signals. The results reveal that, of all conflict- and value-related regions, only the ventral pre-supplementary motor area (or dorsal anterior cingulate cortex) showed a shared neural pattern response to different conflict and affect tasks. These findings challenge recent conclusions that conflict and affect are processed independently, and provide support for integrative views of MFC function.SIGNIFICANCE STATEMENT Multiple theories propose that the MFC, and the dorsal ACC in particular, integrates information related to suboptimal outcomes from different psychological domains (e.g., cognitive control and negative affect) with the aim of adaptively steering behavior. In contrast to recent studies in the field, we provide evidence for the idea that cognitive control and negative affect are integrated in the MFC by showing that a classification algorithm trained on discerning cognitive control (conflict vs no conflict) can predict affect (negative vs positive) in the voxel pattern response of the dorsal ACC/pre-SMA.

Frontoparietal action-oriented codes support novel instruction implementation.

A key aspect of human cognitive flexibility concerns the ability to convert complex symbolic instructions into novel behaviors. Previous research proposes that this transformation is supported by two neurocognitive states: an initial declarative maintenance of task knowledge, and an implementation state necessary for optimal task execution. Furthermore, current models predict a crucial role of frontal and parietal brain regions in this process. However, whether declarative and procedural signals independently contribute to implementation remains unknown. We report the results of an fMRI experiment in which participants executed novel instructed stimulus-response associations. We then used a pattern-tracking procedure to quantify the contribution of format-unique signals during instruction implementation. This revealed independent procedural and declarative representations of novel S-Rs in frontoparietal areas, prior to execution. Critically, the degree of procedural activation predicted subsequent behavioral performance. Altogether, our results suggest an important contribution of frontoparietal regions to the neural architecture that regulates cognitive flexibility.

Fatty acid synthase mediates high glucose-induced EGFR activation in oral dysplastic keratinocytes.

BACKGROUND: Recent studies point to the epidermal growth factor receptor (EGFR) as a critical mediator of type 2 diabetes mellitus (T2DM)-induced renal, cardiac, and ocular complications. T2DM is considered a systemic contributing factor in oral carcinogenesis. Similarly, increased EGFR gene copy number and protein expression strongly predict tumor progression. Yet, the impact of hyperglycemia on EGFR activity in oral potentially malignant disorders remains unclear. We recently reported that fatty acid synthase (FASN), a key de novo lipogenic enzyme, mediates EGFR activation in nicotine-treated oral dysplastic keratinocytes. While in non-malignant tissues FASN expression is extremely low, it is frequently upregulated in several cancers, including oral squamous cell carcinoma. The present study was carried out to investigate whether high glucose conditions trigger pro-oncogenic responses in oral dysplastic keratinocytes via FASN-mediated EGFR activation. METHODS: Cell viability and migration of oral dysplastic keratinocytes were evaluated when exposed to normal (5 mM) or high (20 mM) glucose conditions in the presence of FASN and EGFR inhibitors. Western blotting was also performed to assess changes in FASN protein expression and EGFR activation. RESULTS: Oral dysplastic keratinocytes exposed to high glucose led to EGFR activation in a FASN-dependent manner. Likewise, high glucose significantly enhanced cell viability and migration in a FASN/EGFR-mediated fashion. Notably, EGFR inhibition by the anti-EGFR monoclonal antibody cetuximab significantly reduced the proliferation of FASN-overexpressing oral dysplastic keratinocytes. CONCLUSION: These novel findings suggest that FASN may act as a key targetable metabolic regulator of glucose-induced EGFR oncogenic signaling in oral potentially malignant disorders.

Are all behavioral reward benefits created equally? An EEG-fMRI study.

Reward consistently boosts performance in cognitive tasks. Although many different reward manipulations exist, systematic comparisons are lacking. Reward effects on cognitive control are usually studied using monetary incentive delay (MID; cue-related reward information) or stimulus-reward association (SRA; target-related reward information) tasks. While for MID tasks, evidence clearly implicates reward-triggered global increases in proactive control, it is unclear how reward effects arise in SRA tasks, and in how far such mechanisms overlap during task preparation and target processing. Here, we address these questions with simultaneous EEG-fMRI using a Stroop task with four different block types. In addition to MID and SRA blocks, we used an SRA-task modification with reward-irrelevant cues (C-SRA) and regular reward-neutral Stroop-task blocks. Behaviorally, we observed superior performance for all reward conditions compared to Neutral, and more pronounced reward effects in the SRA and C-SRA blocks, compared to MID blocks. The fMRI data showed similar reward effects in value-related areas for events that signaled reward availability (MID cues and (C-)SRA targets), and comparable reward modulations in cognitive-control regions for all targets regardless of block type. This result pattern was echoed by the EEG data, showing clear markers of valuation and cognitive control, which only differed during task preparation, whereas reward-related modulations during target processing were again comparable across block types. Yet, considering only cue-related fMRI data, C-SRA cues triggered preparatory control processes beyond reward-unrelated MID cues, without simultaneous modulations in typical reward areas, implicating enhanced task preparation that is not directly driven by a concurrent neural reward-anticipation response.

Rethinking the Characterization of Nanoscale Field-Effect Transistors: A Universal Approach.

Standard methods for calculating transport parameters in nanoscale field-effect transistors (FETs), namely carrier concentration and mobility, require a linear connection between the gate voltage and channel conductance; however, this is often not the case. One reason often overlooked is that shifts in chemical and electric potential can partially compensate each other, commonly referred to as quantum capacitance. In nanoscale FETs, capacitance is often unmeasurable and an analytical formula is required, which assumes the conducting channel as metallic and common methods of determining threshold voltage no longer couple properly into transport equations. As present and future FET structures become smaller and have increased channel-gate coupling, this issue will render standard methods impossible to use. This work discusses the validity of common methods of characterization for nanoscale FETs, develops a universal model to determine transport properties by only measuring the threshold voltage of an FET and presents a new parameter to easily classify FETs as either quantum capacitance-limited or metallic approximated charge transport. Also considered in this work is electrical hysteresis from trap states and, in combination with the proposed universal model, novel techniques are introduced to measure and remove the errors associated with these effects often ignored in literature.

Fingerprinting Electronic Structure in Nanomaterials: A Methodology Illustrated by ZnSe Nanowires.

Characterizing point defects that produce deep states in nanostructures is imperative when designing next-generation electronic and optoelectronic devices. Light emission and carrier transport properties are strongly influenced by the energy position and concentration of such states. The primary objective of this work is to fingerprint the electronic structure by characterizing the deep levels using a combined optical and electronic characterization, considering ZnSe nanowires as an example. Specifically, we use low temperature photoluminescence spectroscopy to identify the dominant recombination mechanisms and determine the total defect concentration. The carrier concentration and mobility are then calculated from electron transport measurements using single nanowire field effect transistors, and the measured experimental data were used to construct a model describing the types, energies, and ionized fraction of defects and calculate the deviation from stoichiometry. This metrology is hence demonstrated to provide an unambiguous means to determine a material's electronic structure.

Enhancement of transport properties in single ZnSe nanowire field-effect transistors.

Wide-gap semiconductors are excellent candidates for next-generation optoelectronic devices, including tunable emitters and detectors. ZnSe nanowire-based devices show great promise in blue emission applications, since they can be easily and reproducibly fabricated. However, their utility is limited by deep level defect states that inhibit optoelectronic device performance. The primary objective of this work is to show how the performance of ZnSe nanowire devices improves when nanowires are subjected to a post-growth anneal treatment in a zinc-rich atmosphere. We use low temperature photoluminescence spectroscopy to determine the primary recombination mechanisms and associated defect states. We then characterize the electronic properties of ZnSe nanowire field effect transistors fabricated from both as-grown and Zn-annealed nanowires, and measure an order-of-magnitude improvement to the electrical conductivity and mobility after the annealing treatment. We show that annealing reduces the concentration of zinc vacancies, which are responsible for strong compensation and high amounts of scattering in the as-grown nanowires.

Nicotine induces oral dysplastic keratinocyte migration via fatty acid synthase-dependent epidermal growth factor receptor activation.

Despite advances in diagnostic and therapeutic management, oral squamous cell carcinoma (OSCC) patient survival rates have remained relatively unchanged. Thus, identifying early triggers of malignant progression is critical to prevent OSCC development. Traditionally, OSCC initiation is elicited by the frequent and direct exposure to multiple tobacco-derived carcinogens, and not by the nicotine contained in tobacco products. However, other nicotine-containing products, especially the increasingly popular electronic cigarettes (e-cigs), have unknown effects on the progression of undiagnosed tobacco-induced oral premalignant lesions, specifically in regard to the effects of nicotine. Overexpression of fatty acid synthase (FASN), a key hepatic de novo lipogenic enzyme, is linked to poor OSCC patient survival. Nicotine upregulates hepatic FASN, but whether this response occurs in oral dysplastic keratinocytes is unknown. We hypothesized that in oral dysplastic keratinocytes, nicotine triggers a migratory phenotype through FASN-dependent epidermal growth factor receptor (EGFR) activation, a common pro-oncogenic event supporting oral carcinogenesis. We report that in oral dysplastic cells, nicotine markedly upregulates FASN leading to FASN-dependent EGFR activation and increased cell migration. These results raise potential concerns about e-cig safety, especially when used by former tobacco smokers with occult oral premalignant lesions where nicotine could trigger oncogenic signals commonly associated with malignant progression.

Switch-Independent Task Representations in Frontal and Parietal Cortex.

Alternating between two tasks is effortful and impairs performance. Previous fMRI studies have found increased activity in frontoparietal cortex when task switching is required. One possibility is that the additional control demands for switch trials are met by strengthening task representations in the human brain. Alternatively, on switch trials, the residual representation of the previous task might impede the buildup of a neural task representation. This would predict weaker task representations on switch trials, thus also explaining the performance costs. To test this, male and female participants were cued to perform one of two similar tasks, with the task being repeated or switched between successive trials. Multivoxel pattern analysis was used to test which regions encode the tasks and whether this encoding differs between switch and repeat trials. As expected, we found information about task representations in frontal and parietal cortex, but there was no difference in the decoding accuracy of task-related information between switch and repeat trials. Using cross-classification, we found that the frontoparietal cortex encodes tasks using a generalizable spatial pattern in switch and repeat trials. Therefore, task representations in frontal and parietal cortex are largely switch independent. We found no evidence that neural information about task representations in these regions can explain behavioral costs usually associated with task switching.SIGNIFICANCE STATEMENT Alternating between two tasks is effortful and slows down performance. One possible explanation is that the representations in the human brain need time to build up and are thus weaker on switch trials, explaining performance costs. Alternatively, task representations might even be enhanced to overcome the previous task. Here, we used a combination of fMRI and a brain classifier to test whether the additional control demands under switching conditions lead to an increased or decreased strength of task representations in frontoparietal brain regions. We found that task representations are not modulated significantly by switching processes and generalize across switching conditions. Therefore, task representations in the human brain cannot account for the performance costs associated with alternating between tasks.

Anticipating the good and the bad: A study on the neural correlates of bivalent emotion anticipation and their malleability via attentional deployment.

In everyday life, we often deliberate about affective outcomes of decisions which can be described as ambivalent; i.e. positive and negative at the same time. For example, when looking forward to meet a dear friend at her/his favorite concert although one dislikes the music that is being performed. Thus, anticipation of bivalent emotions and their volitional regulation is an important ingredient of everyday choices. However, previous studies investigating neural substrates involved in anticipating emotional events mostly focused on anticipating either negative emotions (punishment) or positive emotions (reward) in isolation, thus inducing either of them separately. Furthermore, these studies rather focused on the effortful down-regulation of affect (i.e. reducing negative or positive affect), whereas such conflict situations may also require us to deploy attention on and thereby upregulate anticipated emotions in order to resolve a decision conflict (e.g., by focusing on positive consequences while orienting away from negative consequences of that same situation). To address this gap, we performed a series of three fMRI-experiments using simple visual and auditory stimuli in order to (i) determine the neural correlates involved when anticipating a bivalent affective outcome that is both positive and negative at the same time - related to a conflict situation and (ii) investigate their malleability during anticipation via voluntary emotion regulation using attentional focusing. In these studies, we (i) demonstrate that brain areas involved in anticipating positive (ventral striatum) and negative (anterior insula) emotional events are co-activated when anticipating the occurrence of both punishment and reward at the same time and (ii) provide evidence that attention on either the positive or the negative correlates with a shift in activations of these co-activated neural networks and associated anticipated emotions towards either the positive (increased activity in ventral striatum, ventromedial prefrontal cortex, posterior cingulate cortex) or the negative (increased activity in insula) aspect of the upcoming bivalent outcome. In summary, we provide self-report and neural evidence for the assumption that affective brain systems associated with the processing of bivalent anticipated emotions can be voluntarily controlled by cognitive emotion regulation strategies.

The Role of the Parietal Cortex in the Representation of Task-Reward Associations.

Rewards obtained from specific behaviors can and do change across time. To adapt to such conditions, humans need to represent and update associations between behaviors and their outcomes. Much previous work focused on how rewards affect the processing of specific tasks. However, abstract associations between multiple potential behaviors and multiple rewards are an important basis for adaptation as well. In this experiment, we directly investigated which brain areas represent associations between multiple tasks and rewards, using time-resolved multivariate pattern analysis of functional magnetic resonance imaging data. Importantly, we were able to dissociate neural signals reflecting task-reward associations from those related to task preparation and reward expectation processes, variables that were often correlated in previous research. We hypothesized that brain regions involved in processing tasks and/or rewards will be involved in processing associations between them. Candidate areas included the dorsal anterior cingulate cortex, which is involved in associating simple actions and rewards, and the parietal cortex, which has been shown to represent task rules and action values. Our results indicate that local spatial activation patterns in the inferior parietal cortex indeed represent task-reward associations. Interestingly, the parietal cortex flexibly changes its content of representation within trials. It first represents task-reward associations, later switching to process tasks and rewards directly. These findings highlight the importance of the inferior parietal cortex in associating behaviors with their outcomes and further show that it can flexibly reconfigure its function within single trials. Significance statement: Rewards obtained from specific behaviors rarely remain constant over time. To adapt to changing conditions, humans need to continuously update and represent the current association between behavior and its outcomes. However, little is known about the neural representation of behavior-outcome associations. Here, we used multivariate pattern analysis of functional magnetic resonance imaging data to investigate the neural correlates of such associations. Our results demonstrate that the parietal cortex plays a central role in representing associations between multiple behaviors and their outcomes. They further highlight the flexibility of the parietal cortex, because we find it to adapt its function to changing task demands within trials on relatively short timescales.

Similar coding of freely chosen and externally cued intentions in a fronto-parietal network.

Intentional action is essential to human behavior, yet its neural basis remains poorly understood. In order to identify neural networks specifically involved in intentional action, freely chosen and externally cued intentions have previously been contrasted. This has led to the identification of a fronto-parietal network, which is involved in freely choosing one's intentions. However, it remains unclear whether this network encodes specific intentions, or whether it merely reflects general preparatory or control processes correlated with intentional action. Here, we used MVPA on fMRI data to identify brain regions encoding non-motor intentions that were either freely chosen or externally cued. We found that a fronto-parietal network, including the lateral prefrontal cortex, premotor, and parietal cortex, contained information about both freely chosen and externally cued intentions. Importantly, MVPA cross-classification indicated that this network represents the content of our intentions similarly, regardless of whether these intentions are freely chosen or externally cued. This finding suggests that the intention network has a general role in processing and representing intentions independent of their origin.

The Neural Representation of Voluntary Task-Set Selection in Dynamic Environments.

When choosing actions, humans have to balance carefully between different task demands. On the one hand, they should perform tasks repeatedly to avoid frequent and effortful switching between different tasks. On the other hand, subjects have to retain their flexibility to adapt to changes in external task demands such as switching away from an increasingly difficult task. Here, we developed a difficulty-based choice task to investigate how subjects voluntarily select task-sets in predictably changing environments. Subjects were free to choose 1 of the 3 task-sets on a trial-by-trial basis, while the task difficulty changed dynamically over time. Subjects self-sequenced their behavior in this environment while we measured brain responses with functional magnetic resonance imaging (fMRI). Using multivariate decoding, we found that task choices were encoded in the medial prefrontal cortex (dorso-medial prefrontal cortex, dmPFC, and dorsal anterior cingulate cortex, dACC). The same regions were found to encode task difficulty, a major factor influencing choices. Importantly, the present paradigm allowed us to disentangle the neural code for task choices and task difficulty, ensuring that activation patterns in dmPFC/dACC independently encode these 2 factors. This finding provides new evidence for the importance of the dmPFC/dACC for task-selection and motivational functions in highly dynamic environments.