Neural mechanisms of credit assignment for inferred relationships in a structured world

Animals have been proposed to abstract compact representations of a task's structure that could, in principle, support accelerated learning and flexible behavior. Whether and how such abstracted representations may be used to assign credit for inferred, but unobserved, relationships in structured environments are unknown. Here, we develop a novel hierarchical reversal-learning task and Bayesian learning model to assess the computational and neural mechanisms underlying how humans infer specific choice-outcome associations via structured knowledge. We find that the medial prefrontal cortex (mPFC) efficiently represents hierarchically related choice-outcome associations governed by the same latent cause, using a generalized code to assign credit for both experienced and inferred outcomes. Furthermore, mPFC and lateral orbital frontal cortex track the inferred current "position" within a latent association space that generalizes over stimuli. Collectively, these findings demonstrate the importance both of tracking the current position in an abstracted task space and efficient, generalizable representations in prefrontal cortex for supporting flexible learning and inference in structured environments.

Cerebellar contributions to a brainwide network for flexible behavior

The cerebellum regulates nonmotor behavior, but the routes by which it exerts its influence are not well characterized. Here we report a necessary role for posterior cerebellum in guiding flexible behavior, acting through a network of diencephalic and neocortical structures. After chemogenetic inhibition of Purkinje cells in lobule VI or crus I, high-throughput automated analysis of complex whole-body movement revealed deficiencies in adaptation across days to an open field environment. Neither perturbation affected gait, within-day open-field adaptation, or location preference. In a Y-maze task, mice could learn but were impaired in their ability to reverse their initial choice. To map targets of perturbation, we imaged c-Fos activation in cleared whole brains using light-sheet microscopy. Reversal learning activated diencephalic regions and associative neocortical regions. Distinctive subsets of structures were altered by perturbation of lobule VI (thalamus and habenula) and crus I (hypothalamus and prelimbic/orbital cortex), and both perturbations influenced anterior cingulate and infralimbic cortex. Taken together, these experiments reveal parts of a brainwide system for cerebellar influence to guide flexible learning.

Dopamine, Cognitive Flexibility, and IQ: Epistatic Catechol-O-MethylTransferase:DRD2 Gene–Gene Interactions Modulate Mental Rigidity

Cognitive flexibility has been hypothesized to be neurochemically rooted in dopamine neurotransmission. Nonetheless, underpowered sample sizes and contradictory meta-analytic findings have obscured the role of dopamine genes in cognitive flexibility and neglected potential gene–gene interactions. In this largest neurocognitive-genetic study to date (n = 1400), single nucleotide polymorphisms associated with elevated prefrontal dopamine levels (catechol-O-methyltransferase; rs4680) and diminished striatal dopamine (C957T; rs6277) were both implicated in Wisconsin Card Sorting Test performance. Crucially, however, these genetic effects were only evident in low-IQ participants, suggesting high intelligence compensates for, and eliminates, the effect of dispositional dopamine functioning on flexibility. This interaction between cognitive systems may explain and resolve previous empirical inconsistencies in highly educated participant samples. Moreover, compensatory gene–gene interactions were discovered between catechol-O-methyltransferase and DRD2, such that genotypes conferring either elevated prefrontal dopamine or diminished striatal dopamine—via heightened striatally concentrated D2 dopamine receptor availability—are sufficient for cognitive flexibility, but neither is necessary. The study has therefore revealed a form of epistatic redundancy or substitutability among dopamine systems in shaping adaptable thought and action, thus defining boundary conditions for dopaminergic effects on flexible behavior. These results inform theories of clinical disorders and psychopharmacological interventions and uncover complex fronto-striatal synergies in human flexible cognition.

Topological insights into the neural basis of flexible behavior

1AbstractIt is widely accepted that there is an inextricable link between neural computations, biological mechanisms, and behavior, but there exists no framework that can simultaneously explain all three. Here, we show that topological data analysis (TDA) provides that necessary bridge. We demonstrate that cognitive processes change the topological description of the shared activity of populations of visual neurons. These topological changes provide uniquely strong constraints on a mechanistic model, explain behavior, and, via a link with network control theory, reveal a tradeoff between improving sensitivity to subtle visual stimulus changes and increasing the chance that the subject will stray off task. These discoveries provide a blueprint for using TDA to uncover the biological and computational mechanisms by which cognition affects behavior in health and disease.

Dynamic Transitions between Neural States Are Associated with Flexible Task Switching during a Memory Task

Flexible behavior requires switching between different task conditions. It is known that such task switching is associated with costs in terms of slowed RT, reduced accuracy, or both. The neural correlates of task switching have usually been studied by requiring participants to switch between distinct task conditions that recruit different brain networks. Here, we investigated the transition of neural states underlying switching between two opposite memory-related processes (i.e., memory retrieval and memory suppression) in a memory task. We investigated 26 healthy participants who performed a think/no-think task while being in the fMRI scanner. Behaviorally, we show that it was more difficult for participants to suppress unwanted memories when a no-think was preceded by a think trial instead of another no-think trial. Neurally, we demonstrate that think–no-think switches were associated with an increase in control-related and a decrease in memory-related brain activity. Neural representations of task condition, assessed by decoding accuracy, were lower immediately after task switching compared with the nonswitch transitions, suggesting a switch-induced delay in the neural transition toward the required task condition. This suggestion is corroborated by an association between condition-specific representational strength and condition-specific performance in switch trials. Taken together, we provided neural evidence from the time-resolved decoding approach to support the notion that carryover of the previous task set activation is associated with the switching cost, leading to less successful memory suppression.

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

Background Conceptual 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). Methods Children 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. Results As 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. Conclusion Our 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.

The Value of Ho Chi Minh's Ideology, Morality and Style to the Vietnamese Nation Today

This article aims to clarify the basic contents of leader Ho Chi Minh's ideology, morality and style that are valuable to the Vietnamese nation. In fact, Vietnam has been proving the miraculous vitality of Ho Chi Minh's ideology on the path and goals of national development, on the strategy of great national unity and international solidarity, innovative thinking, culture and humanities. His moral example and views on revolutionary ethical standards and ethical practice principles are the red thread throughout the progress of progressive and civilized human development. His style is extremely lively, natural, unique, attractive, magical in daily activities and behavior, which is shown as independent, self-directed and creative thinking style; scientific, democratic and mass working style; modest, polite, sincere, warm, natural and flexible behavior style; simple, clean, moderate, moderate living style. These legacies form a consistent whole in Ho Chi Minh's people, have deep scientific, theoretical and practical values ​​in terms of ethics and aesthetics, consistent with the history of the Vietnamese nation and the development trend of mankind.

PZT Actuators’ Effect on Vibration Control of the PRRRP 2-DOF Flexible Parallel Manipulator

Thanks to their advantages over rigid ones, interest for lightweight parallel manipulator was increased. Besides, structural flexibility effects at high operational speeds are more significant. Thus, developing an appropriate model for the assessment of the dynamic properties of flexible mechanisms and linkages to gain effective vibration control will raise high demand. Therefore, this paper represents the dynamic and kinematic modeling using the assumed mode method and first-type Lagrange equations of the 2-DOF planar parallel manipulator with two flexible links. To truly predict vibrations of the manipulator without any major simplifying assumptions, nonlinear dynamic modeling, which thoroughly attempts to represent the flexible behavior of the links, is considered. As a result, an active damping approach is being studied with PZT actuators. The results show that this approach is effective in damping the vibrations of the links that give accurate trajectory control.

Contextual gating of motivationally-relevant stimuli in the mouse nucleus accumbens

Neural activity in the nucleus accumbens (NAc) is thought to track fundamentally value- centric quantities such as current or future expected reward, reward prediction errors, the value of work, opportunity cost, and approach vigor. However, the NAc also contributes to flexible behavior in ways that are difficult to explain based on value signals alone, raising the question of if and how non-value signals are encoded in NAc. We recorded NAc neural ensembles while head-fixed mice performed a context-dependent odor discrimination task, and extracted single-unit and population-level correlates of task features. We found coding for context-setting cues that modulate the stimulus-outcome association of subsequently presented reward-predictive cues. This context signal occupied a subspace orthogonal to classic value representations, suggesting that it does not interfere with value-related NAc output. Finally, we show that the context signal is predictive of subsequent value coding, supporting a circuit-level gating model for how the NAc contributes to behavioral flexibility and providing a novel population-level perspective from which to view NAc computations.