Rostrolateral Prefrontal Cortex Research Articles

Neural Correlates of Analogical Reasoning on Syntactic Patterns.

Analogical reasoning is central to thought and learning. However, previous neuroscience studies have focused mainly on neural substrates for visuospatial and semantic analogies. There has not yet been research on the neural correlates of analogical reasoning on syntactic patterns generated by the syntactic rules, a key feature of human language faculty. The present investigation took an initial step to address this paucity. Twenty-four participants, whose brain activity was monitored by fMRI, engaged in first-order and second-order relational judgments of syntactic patterns as well as simple and complex working memory tasks. After scanning, participants rated the difficulty of each step during analogical reasoning; these ratings were related to signal intensities in activated regions of interest using Spearman correlation analyses. After prior research, differences in activation levels during second-order and first-order relational judgments were taken as evidence of analogical reasoning. These analyses showed that analogical reasoning on syntactic patterns recruited brain regions consistent with those supporting visuospatial and semantic analogies, including the anterior and posterior parts of the left middle frontal gyrus, anatomically corresponding to the left rostrolateral pFC and the left dorsolateral pFC. The correlation results further revealed that the posterior middle frontal gyrus might be involved in analogical access and mapping with syntactic patterns. Our study is the first to investigate the process of analogical reasoning on syntactic patterns at the neurobiological level and provide evidence of the specific functional roles of related regions during subprocesses of analogical reasoning.

Impaired creative cognition after surgery for an IDH-mutated glioma: A proof-of-concept study

Assessment of high cognitive functions, such as creativity, is often overlooked in medical practice. However, it is crucial to understand the impact of brain tumors, specifically low-grade gliomas, on creative cognition, as these tumors predominantly affect brain regions associated with cognitive creativity. In this study, we investigated creative cognition using the Alternative Uses Task (AUT) and the Combination of Associates Task (CAT) in a cohort of 29 patients who underwent brain surgery for a low-grade glioma, along with 27 control participants. While the group of patients did not exhibit deficits in clinical neuropsychological assessments, our results revealed significant impairment in generating original and creative ideas compared to the control group. Furthermore, when analyzing the specific brain regions affected by the tumors, patients with lesions overlapping the left rostro-lateral prefrontal cortex, a critical region for creativity, displayed more pronounced impairments in the CAT compared to patients with lesions outside this region. These findings provide proof of concept that patients can experience impaired creative cognition following surgery for low-grade glioma, highlighting the importance of assessing higher-order cognitive functions, including creativity, in neurosurgical patients. Moreover, beyond its clinical relevance, our study contributes to advancing our understanding of the neuroscience of creativity.

Monkey Dorsolateral Prefrontal Cortex Represents Abstract Visual Sequences during a No-Report Task.

Monitoring sequential information is an essential component of our daily lives. Many of these sequences are abstract, in that they do not depend on the individual stimuli, but do depend on an ordered set of rules (e.g., chop then stir when cooking). Despite the ubiquity and utility of abstract sequential monitoring, little is known about its neural mechanisms. Human rostrolateral prefrontal cortex (RLPFC) exhibits specific increases in neural activity (i.e., "ramping") during abstract sequences. Monkey dorsolateral prefrontal cortex (DLPFC) has been shown to represent sequential information in motor (not abstract) sequence tasks, and contains a subregion, area 46, with homologous functional connectivity to human RLPFC. To test the prediction that area 46 may represent abstract sequence information, and do so with parallel dynamics to those found in humans, we conducted functional magnetic resonance imaging (fMRI) in three male monkeys. When monkeys performed no-report abstract sequence viewing, we found that left and right area 46 responded to abstract sequential changes. Interestingly, responses to rule and number changes overlapped in right area 46 and left area 46 exhibited responses to abstract sequence rules with changes in ramping activation, similar to that observed in humans. Together, these results indicate that monkey DLPFC monitors abstract visual sequential information, potentially with a preference for different dynamics in the two hemispheres. More generally, these results show that abstract sequences are represented in functionally homologous regions across monkeys and humans.SIGNIFICANCE STATEMENT Daily, we complete sequences that are "abstract" because they depend on an ordered set of rules (e.g., chop then stir when cooking) rather than the identity of individual items. Little is known about how the brain tracks, or monitors, this abstract sequential information. Based on previous human work showing abstract sequence related dynamics in an analogous area, we tested whether monkey dorsolateral prefrontal cortex (DLPFC), specifically area 46, represents abstract sequential information using awake monkey functional magnetic resonance imaging (fMRI). We found that area 46 responded to abstract sequence changes, with a preference for more general responses on the right and dynamics similar to humans on the left. These results suggest that abstract sequences are represented in functionally homologous regions across monkeys and humans.

Neural correlates of mindful disengagement from worry.

Uncontrollable worry is a hallmark of generalized anxiety disorder and a transdiagnostic feature of psychopathology. Mindfulness-based strategies show promise for treating worry, but it is unknown which specific strategies are most beneficial, and how these skills might operate on a neurobiological level. We recruited 40 participants with clinically significant worry to undergo functional magnetic resonance imaging while engaging in real-time, idiographic worry and instructed disengagement using two mindfulness strategies (focused attention, acceptance) and one comparison strategy (suppression). Hypotheses were preregistered and partially supported. All disengagement strategies downregulated default mode and upregulated frontoparietal and salience networks, suggesting some shared mechanisms. Focused attention was most effective for promoting disengagement and elicited decreased activity in cognitive control and sensorimotor regions. Successful disengagement was associated with increased activity in rostrolateral prefrontal cortex and functional connectivity between posterior cingulate and primary somatosensory cortex. Findings support the role of cognitive control and somatosensory networks in disengagement from worry and suggest common and distinct mechanisms of disengagement, with focused attention a particularly promising strategy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Representations of Predicted Uncertainty in Prefrontal and Sensory Cortex Prior to Search

Theories of attention often focus on how known, definitive visual features are represented prior to the onset of a task. However, objects in the real-world are dynamic and have features that change overtime, creating uncertainty in their future appearance. This means that observers must make predictions about how the target could look. Representing the uncertainty of target features is essential for predictive processes, yet how the brain represents the uncertainty of upcoming visual stimuli is unclear. In this study, we investigate the brain regions that encode the distribution of possible target features prior to the onset of a visual search task. In each trial, participants (N=7) heard a cue-tone (high- or low-pitch) which corresponded to the central tendency of a target color (pink-orange, or blue-green, respectively). However, the true target color was drawn from a Gaussian distribution centered on the predicted color with either high or low variability, depending on the block. In each trial, there was one distractor object with a randomly selected color. Thus, to optimally represent the target object participants had to know both the central tendency of the target color, as well as the distribution of possible colors the target could have (i.e., the uncertainty). Using a combination of linear decoders and representational similarity analysis, we show the regions of early visual cortex and rostro-lateral prefrontal cortex (RLPFC) carry representations of the predicted target and the uncertainty of those predictions. Further, univariate analyses at the time of search found that RLPFC, medial frontal gyrus, and intraparietal cortex also coded prediction errors for the target object which depended on the variability of the target distribution. These results suggest that a network of sensory and frontal regions carry joint codes for both the mean and uncertainty of the distribution of possible upcoming search targets.

Pragmatic inferences: Neuroimaging of ad-hoc implicatures

During conversation, comprehenders often make pragmatic inferences, or implicatures. Our study concerns ad-hoc implicatures, which are quantity-based implicatures. For example, the sentence “I walked Lassie”, where the addressee knows that the speaker has 2 dogs, signals to the addressee that the speaker wanted to convey an enriched meaning (i.e., she walked Lassie, but not the other dog). On some accounts, it is assumed that these implicatures are derived similarly to the well-studied scalar implicatures. Yet, ad-hoc implicatures received little attention. In the current study, we used fMRI to further uncover the mechanisms that support pragmatic inferences, and specifically ad-hoc implicatures. In our judgment task, we first presented a context picture with several objects, then the target sentence (sans picture) which referred to either the subset (implicature condition) or the whole set of objects (no-implicature condition), and finally asked participants to judge whether a final picture matched the target sentence. Comparing the implicature and no-implicature conditions, we observed activations in the rostrolateral prefrontal cortex, which we linked to inference generation, and in the right inferior parietal lobule, which we linked to theory of mind or attention shift. We also performed an ROI analysis, examining activations related to ad-hoc implicatures in regions previously linked to scalar implicatures and to other types of context-based implicatures, showing overlaps and dissimilarities in both cases. Thus, our results are not completely in line with theories that argue for one type of processing in the derivation of pragmatic inferences. • Highlights for “Pragmatic inferences: Neuroimaging of ad-hoc implicatures”. • The neural correlates of ad-hoc implicatures have not been examined. • Activation in the rlPFC was linked to inference generation. • Activation in the right iPL was linked to mind reading or attention shift. • ROI analysis showed Overlap and dissimilarity with other pragmatic inferences.

Brain Anatomy Alterations and Mental Health Challenges Correlate to Email Addiction Tendency.

Despite the widespread use of email, our knowledge regarding the consequences of email addiction is lacking. The purpose of this study was to develop an email addiction tendency scale to evaluate its correlation to behavior and brain structure. Following this, the validity and reliability of the developed scale was investigated. We used voxel-based morphometry, correlation, and univariate regression analysis to assess the relationships between email addiction tendency scores and regional gray and white matter volumes, depression, and nonverbal reasoning abilities in a large sample of healthy young adults (n = 1152; mean age, 20.69 ± 1.84 years). The content validity ratio, content validity index, principal component analysis, and confirmatory factorial analysis all showed that the email addiction tendency scale (EATS) has high validity. Additionally, the Cronbach’s alpha internal consistency and split-half reliability coefficient showed that the EATS has high reliability. We found that email addiction tendency scores were significantly negatively correlated with nonverbal reasoning. We also observed that the email addiction tendency scores were significantly and positively correlated with depression symptom severity and gray matter volume of the left rostrolateral prefrontal cortex (RLPC) in subjects. These results indicate that email addiction tendency is associated with lower mental health outcomes and increased GMV in the left RLPC.

Long-term Meditation Training Is Associated with Enhanced Subjective Attention and Stronger Posterior Cingulate-Rostrolateral Prefrontal Cortex Resting Connectivity.

Mindfulness meditation has been shown to increase resting-state functional connectivity (rsFC) between the posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC), which is thought to reflect improvements in shifting attention to the present moment. However, prior research in long-term meditation practitioners lacked quantitative measures of attention that would provide a more direct behavioral correlate and interpretational anchor for PCC-DLPFC connectivity and was inherently limited by small sample sizes. Moreover, whether mindfulness meditation primarily impacts brain function locally, or impacts the dynamics of large-scale brain networks, remained unclear. Here, we sought to replicate and extend prior findings of increased PCC-DLPFC rsFC in a sample of 40 long-term meditators (average practice = 3759 hr) who also completed a behavioral assay of attention. In addition, we tested a network-based framework of changes in interregional connectivity by examining network-level connectivity. We found that meditators had stronger PCC-rostrolateral prefrontal cortex (RLPFC) rsFC, lower connector hub strength across the default mode network, and better subjective attention, compared with 124 meditation-naive controls. Orienting attention positively correlated with PCC-RLPFC connectivity and negatively correlated with default mode network connector hub strength. These findings provide novel evidence that PCC-RLPFC rsFC may support attention orienting, consistent with a role for RLPFC in the attention shifting component of metacognitive awareness that is a core component of mindfulness meditation training. Our results further demonstrate that long-term mindfulness meditation may improve attention and strengthen the underlying brain networks.

Reward Value Enhances Sequence Monitoring Ramping Dynamics as Ending Rewards Approach in the Rostrolateral Prefrontal Cortex.

Many fundamental human behaviors contain multiple sequences performed to reach a desired outcome, such as cooking. Reward is inherently associated with sequence completion and has been shown to generally enhance cognitive control. However, the impact of reward on cognitive sequence processing remains unexplored. To address this key question, we focused on the rostrolateral prefrontal cortex (RLPFC). This area is necessary and exhibits increasing (“ramping”) activation during sequences, a dynamic that may be related to reward processing in other brain regions. To separate these dynamics, we designed a task where reward was only provided after multiple four-item sequences (“iterations”), rather than each individual sequence. Using fMRI in humans, we investigated three possible interactions of reward and sequential control signals in RLPFC: (1) with the visibility of sequential cues, i.e., memory; (2) equally across individual sequence iterations; and (3) differently across individual sequence iterations (e.g., increasing as reward approaches). Evidence from previous, nonsequential cognitive control experiments suggested that reward would uniformly change RLPFC activity across iterations and may depend on the visibility of cues. However, we found the influence of reward on RLPFC ramping increased across sequence iterations and did not interact with memory. These results suggest an active, predictive, and distinctive role for RLPFC in sequence monitoring and integration of reward information, consistent with extant literature demonstrating similar accelerating reward-related dopamine dynamics in regions connected to RLPFC. These results have implications for understanding sequential behavior in daily life, and when they go awry in disorders such as addiction.

Neural correlates of schema-dependent episodic memory and association with behavioral flexibility in autism spectrum disorders and typical development

BackgroundConceptual knowledge frameworks termed schemas facilitate memory formation and are posited to support flexible behavior. In adults, the medial temporal lobe (MTL) and medial prefrontal cortex (mPFC) trade-off in supporting schema-based memory formation, such that encoding of subsequently remembered schema-congruent information relies on mPFC, whereas schema-incongruent information relies on MTL. Whether this is true in the immature brain and relates to behavioral flexibility is unknown. In this preliminary investigation, we aimed to replicate the adult findings in typically developing (TD) children and to investigate the relevance to behavioral flexibility by examining a disorder with pathognomonic behavioral rigidity, autism spectrum disorder (ASD).MethodsChildren completed an associative subsequent memory paradigm, encoding object-scene pairs in an MRI scanner and subsequently completing a recognition test outside the scanner after a delay. Recognition performance was back sorted to construct remembered vs forgotten contrasts. One-way ANOVAS were conducted in MTL and mPFC masks for schema-congruency, followed by congruency by flexibility scores. Exploratory analyses were then conducted within the whole brain.ResultsAs reported in adults, episodic memory was strongest for schema-congruent object-scene pairs, followed by intermediate pairs, and lowest for schema-incongruent pairs in both TD and ASD groups. However, the trade-off between mPFC and MTL in TD children differed from adult reports such that mPFC supported memory for intermediate schema-congruency and left anterior MTL supported memory for schema-congruent pairs. In ASD, mPFC engagement interacted with flexibility such that activation supporting memory for intermediate schema-congruency varied with parent-reported flexibility and was higher in those with more flexible behavior. A similar interaction was also observed in both the left dorsolateral and rostrolateral PFC in whole-brain analysis.ConclusionOur findings provide the first preliminary evidence for the association of schema-based episodic memory formation and behavioral flexibility, an executive function impaired in multiple developmental disorders. Upon replication, this line of research holds promise for memory-based interventions addressing executive problems of behavioral rigidity.

Learning and Representation of Hierarchical Concepts in Hippocampus and Prefrontal Cortex.

A key aspect of conceptual knowledge is that it can be flexibly applied at different levels of abstraction, implying a hierarchical organization. It is yet unclear how this hierarchical structure is acquired and represented in the brain. Here we investigate the computations underlying the acquisition and representation of the hierarchical structure of conceptual knowledge in the hippocampal-prefrontal system of 32 human participants (22 females). We assessed the hierarchical nature of learning during a novel tree-like categorization task via computational model comparisons. The winning model allowed to extract and quantify estimates for accumulation and updating of hierarchical compared with single-feature-based concepts from behavior. We find that mPFC tracks accumulation of hierarchical conceptual knowledge over time, and mPFC and hippocampus both support trial-to-trial updating. As a function of those learning parameters, mPFC and hippocampus further show connectivity changes to rostro-lateral PFC, which ultimately represented the hierarchical structure of the concept in the final stages of learning. Our results suggest that mPFC and hippocampus support the integration of accumulated evidence and instantaneous updates into hierarchical concept representations in rostro-lateral PFC.SIGNIFICANCE STATEMENT A hallmark of human cognition is the flexible use of conceptual knowledge at different levels of abstraction, ranging from a coarse category level to a fine-grained subcategory level. While previous work probed the representational geometry of long-term category knowledge, it is unclear how this hierarchical structure inherent to conceptual knowledge is acquired and represented. By combining a novel hierarchical concept learning task with computational modeling of categorization behavior and concurrent fMRI, we differentiate the roles of key concept learning regions in hippocampus and PFC in learning computations and the representation of a hierarchical category structure.

Predictive processing, cognitive control, and tonality stability of music: An fMRI study of chromatic harmony

The present study aimed at identifying the brain regions which preferentially responded to music with medium degrees of key stability. There were three types of auditory stimuli. Diatonic music based strictly on major and minor scales has the highest key stability, whereas atonal music has the lowest key stability. Between these two extremes, chromatic music is characterized by sophisticated uses of out-of-key notes, which challenge the internal model of musical pitch and lead to higher precision-weighted prediction error compared to diatonic and atonal music. The brain activity of 29 adults with excellent relative pitch was measured with functional magnetic resonance imaging while they listened to diatonic music, chromatic music, and atonal random note sequences. Several frontoparietal regions showed significantly greater response to chromatic music than to diatonic music and atonal sequences, including the pre-supplementary motor area (extending into the dorsal anterior cingulate cortex), dorsolateral prefrontal cortex, rostrolateral prefrontal cortex, intraparietal sulcus, and precuneus. We suggest that these frontoparietal regions may support working memory processes, hierarchical sequencing, and conflict resolution of remotely related harmonic elements during the predictive processing of chromatic music. This finding suggested a possible correlation between precision-weighted prediction error and the frontoparietal regions implicated in cognitive control.

Neural correlates of improved inductive reasoning ability in abacus‐trained children: A resting state fMRI study

Abacus-based mental calculation (AMC) training may improve mathematics-related abilities and transfer to other cognitive domains. Thus, it was hypothesized that inductive reasoning abilities can be improved by AMC training given the overlapping cognitive processes and neural correlates between AMC and inductive reasoning. The aim of the current study was to examine the underlying neurobiological mechanisms of this possible adaption by resting-state functional magnetic resonance imaging (rs-fMRI). Sixty-three children were randomly assigned to either the AMC-trained or the nontrained group. The AMC-trained group was required to perform abacus training for 2 hours per week for 5 years whereas the nontrained group was not required to perform any abacus training. Each participant's rs-fMRI data were collected after abacus training, and regional homogeneity (ReHo) analysis was performed to determine the neural activity differences between groups. The participants' posttraining mathematical ability, intelligence quotients, and inductive reasoning ability were recorded and evaluated. The results revealed that AMC-trained children exhibited a significantly higher mathematical ability and inductive reasoning performance and higher ReHo in the rostrolateral prefrontal cortex (RLPFC) compared to the nontrained group. In particular, the increased ReHo in the RLPFC was found to be positively correlated with improved inductive reasoning performance. Our findings suggest that rs-fMRI may reflect the modulation of training in task-related networks.

Alternation of Resting-State Functional Connectivity Between Visual Cortex and Hypothalamus in Guinea Pigs With Experimental Glucocorticoid Enhanced Myopia After the Treatment of Electroacupuncture

Excessive glucocorticoids (GC) may lead to the aggravation of several basic diseases including myopia, due to plasma hormone imbalances associated with the hypothalamic–pituitary–adrenal axis (HPAA). Electroacupuncture (EA) is an effective therapeutic method to treat many diseases, although it remains unclear whether EA at acupoints on the foot or back would be effective in treating eye diseases. It was recently found that visual cortex activity for responses to visual stimuli with spatial frequency and resting-state functional connectivity (FC) between the supramarginal gyrus and rostrolateral prefrontal cortex was significantly reduced in patients with high myopia. The present study aims to investigate the role of the alternation of resting-state FC among the bilateral visual cortex and hypothalamus in exerting anti-myopia effects of EA in GC-enhanced lens-induced myopic (LIM) guinea pigs such that the mechanisms of EA to treat GC-enhanced myopia at Shenshu (BL23) acupoints can be probed. To confirm the effects of EA, ocular parameters including axial length and GC-associated physiological parameters such as animal appearance, behavior, bodyweight, and levels of four HPAA-associated plasma hormones [free triiodothyronine (FT3), free thyroxine (FT4), estradiol (E2), and testosterone (T)] were also collected. Increased resting-state FC between the left and right visual cortex was detected in GC-enhanced lens-induced myopic guinea pigs with EA at BL23 acupoints (LIM+GC+EA) guinea pigs compared to GC-enhanced lens-induced myopic guinea pigs with EA at sham acupoints (LIM+GC+Sham) guinea pigs, as well as suppressed myopia and recovery of symptoms initially caused by overdose of GC. Recovered symptoms included improved animal appearance, behavior, bodyweight, and HPAA-associated plasma hormone levels were observed after 4 weeks of EA treatment. In contrast, the LIM+GC+Sham group showed decreased FC with elongation of axial length for myopization as compared to the control group and LIM group and exhibited a deterioration in physiological parameters including reduced body weight and balance disruption in the four measured HPAA-associated plasma hormones. Our findings suggest that EA could effectively treat GC-enhanced myopia by increasing resting-state FC between the left and right visual cortices, which may be pivotal to further understanding the application and mechanisms of EA in treating GC-enhanced myopia.

Relational Integration in the Human Brain: A Review and Synthesis.

Relational integration is required when multiple explicit representations of relations between entities must be jointly considered to make inferences. We provide an overview of the neural substrate of relational integration in humans and the processes that support it, focusing on work on analogical and deductive reasoning. In addition to neural evidence, we consider behavioral and computational work that has informed neural investigations of the representations of individual relations and of relational integration. In very general terms, evidence from neuroimaging, neuropsychological, and neuromodulatory studies points to a small set of regions (generally left lateralized) that appear to constitute key substrates for component processes of relational integration. These include posterior parietal cortex, implicated in the representation of first-order relations (e.g., A:B); rostrolateral pFC, apparently central in integrating first-order relations so as to generate and/or evaluate higher-order relations (e.g., A:B::C:D); dorsolateral pFC, involved in maintaining relations in working memory; and ventrolateral pFC, implicated in interference control (e.g., inhibiting salient information that competes with relevant relations). Recent work has begun to link computational models of relational representation and reasoning with patterns of neural activity within these brain areas.

Where Sounds Occur Matters: Context Effects Influence Processing of Salient Vocalisations.

The social context in which a salient human vocalisation is heard shapes the affective information it conveys. However, few studies have investigated how visual contextual cues lead to differential processing of such vocalisations. The prefrontal cortex (PFC) is implicated in processing of contextual information and evaluation of saliency of vocalisations. Using functional Near-Infrared Spectroscopy (fNIRS), we investigated PFC responses of young adults (N = 18) to emotive infant and adult vocalisations while they passively viewed the scenes of two categories of environmental contexts: a domestic environment (DE) and an outdoors environment (OE). Compared to a home setting (DE) which is associated with a fixed mental representation (e.g., expect seeing a living room in a typical house), the outdoor setting (OE) is more variable and less predictable, thus might demand greater processing effort. From our previous study in Azhari et al. (2018) that employed the same experimental paradigm, the OE context was found to elicit greater physiological arousal compared to the DE context. Similarly, we hypothesised that greater PFC activation will be observed when salient vocalisations are paired with the OE compared to the DE condition. Our finding supported this hypothesis: the left rostrolateral PFC, an area of the brain that facilitates relational integration, exhibited greater activation in the OE than DE condition which suggests that greater cognitive resources are required to process outdoor situational information together with salient vocalisations. The result from this study bears relevance in deepening our understanding of how contextual information differentially modulates the processing of salient vocalisations.

The Neurocognitive Correlates of Human Reasoning: A Meta-analysis of Conditional and Syllogistic Inferences.

Inferring knowledge is a core aspect of human cognition. We can form complex sentences connecting different pieces of information, such as in conditional statements like "if someone drinks alcohol, then they must be older than 18." These are relevant for causal reasoning about our environment and allow us to think about hypothetical scenarios. Another central aspect to forming complex statements is to quantify about sets, such as in "some apples are green." Reasoning in terms of the ability to form these statements is not yet fully understood, despite being an active field of interdisciplinary research. On a theoretical level, several conceptual frameworks have been proposed, predicting diverging brain activation patterns during the reasoning process. We present a meta-analysis comprising the results of 32 neuroimaging experiments about reasoning, which we subdivided by their structure, content, and requirement for world knowledge. In conditional tasks, we identified activation in the left middle and rostrolateral pFC and parietal regions, whereas syllogistic tasks elicit activation in Broca's complex, including the BG. Concerning the content differentiation, abstract tasks exhibit activation in the left inferior and rostrolateral pFC and inferior parietal regions, whereas content tasks are in the left superior pFC and parieto-occipital regions. The findings clarify the neurocognitive mechanisms of reasoning and exhibit clear distinctions between the task's type and content. Overall, we found that the activation differences clarify inconsistent results from accumulated data and serve as useful scaffolding differentiations for theory-driven interpretations of the neuroscientific correlates of human reasoning.

Dissociable neural correlates of uncertainty underlie different exploration strategies

Most real-world decisions involve a delicate balance between exploring unfamiliar alternatives and committing to the best known option. Previous work has shown that humans rely on different forms of uncertainty to negotiate this "explore-exploit” trade-off, yet the neural basis of the underlying computations remains unclear. Using fMRI (n = 31), we find that relative uncertainty is represented in right rostrolateral prefrontal cortex and drives directed exploration, while total uncertainty is represented in right dorsolateral prefrontal cortex and drives random exploration. The decision value signal combining relative and total uncertainty to compute choice is reflected in motor cortex activity. The variance of this signal scales with total uncertainty, consistent with a sampling mechanism for random exploration. Overall, these results are consistent with a hybrid computational architecture in which different uncertainty computations are performed separately and then combined by downstream decision circuits to compute choice.

The Rostrolateral Prefrontal Cortex Mediates a Preference for High-Agency Environments.

The ability to exert flexible instrumental control over one's environment is a defining feature of adaptive decision-making. Here, we investigated neural substrates mediating a preference for environments with greater instrumental divergence, the distance between outcome probability distributions associated with alternative actions. A formal index of agency, instrumental divergence allows an organism to flexibly obtain the currently most desired outcome as preferences change. As such, it may have intrinsic utility, guiding decisions toward environments that maximize instrumental power. Consistent with this notion, we found that a measure of expected value that treats instrumental divergence as a reward surrogate provided a better account of male and female human participants' choice preferences than did a conventional model, sensitive only to monetary reward. Using model-based fMRI, we found that activity in the rostrolateral and ventromedial PFC, regions associated with abstract cognitive inferences and subjective value computations, respectively, scaled with the divergence-based account of expected value. Implications for a neural common currency of information theoretic and motivational variables are discussed.SIGNIFICANCE STATEMENT Agency is a central concept in philosophy and psychology. While research thus far has focused on cognitive and perceptual measures of agency, recent work demonstrating a strong preference for high-agency environments indicates a salient motivational dimension. Here, using instrumental divergence, the distance between outcome distributions associated with alternative actions, as a formal index of agency, we found that brain regions associated with directed exploration and subjective value computations, respectively, were selectively modulated by a model that treated agency as a reward surrogate, over models that assigned utility only to monetary payoffs. In a subset of regions, such effects were predicted by the influence of instrumental divergence on economic choice preferences. Our results elucidate neural mechanisms mediating the utility of agency.

Adolescents at clinical high risk for psychosis show qualitatively altered patterns of activation during rule learning

BackgroundThe ability to flexibly apply rules to novel situations is a critical aspect of adaptive human behavior. While executive function deficits are known to appear early in the course of psychosis, it is unclear which specific facets are affected. Identifying whether rule learning is impacted at the early stages of psychosis is necessary for truly understanding the etiology of psychosis and may be critical for designing novel treatments. Therefore, we examined rule learning in healthy adolescents and those meeting criteria for clinical high risk (CHR) for psychosis. Methods24 control and 22 CHR adolescents underwent rapid, high-resolution fMRI while performing a paradigm which required them to apply novel or practiced task rules. ResultsPrevious work has suggested that practiced rules rely on rostrolateral prefrontal cortex (RLPFC) during rule encoding and dorsolateral prefrontal cortex (DLPFC) during task performance, while novel rules show the opposite pattern. We failed to replicate this finding, with greater activity for novel rules during performance. Comparing the HC and CHR group, there were no statistically significant effects, but an effect size analysis found that the CHR group showed less activation during encoding and greater activation during performance. This suggests the CHR group may use less efficient reactive control to retrieve task rules at the time of task performance, rather than proactively during rule encoding. ConclusionsThese findings suggest that flexibility is qualitatively altered in the clinical high risk state, however, more data is needed to determine whether these deficits predict disease progression.