The Geometry of Abstraction in the Hippocampus and Prefrontal Cortex.

The curse of dimensionality plagues models of reinforcement learning and decision making. The process of abstraction solves this by constructing variables describing features shared by different instances, reducing dimensionality and enabling generalization in novel situations. Here, we characterized neural representations in monkeys performing a task described by different hidden and explicit variables. Abstraction was defined operationally using the generalization performance of neural decoders across task conditions not used for training, which requires a particular geometry of neural representations. Neural ensembles in prefrontal cortex, hippocampus, and simulated neural networks simultaneously represented multiple variables in a geometry reflecting abstraction but that still allowed a linear classifier to decode a large number of other variables (high shattering dimensionality). Furthermore, this geometry changed in relation to task events and performance. These findings elucidate how the brain and artificial systems represent variables in an abstract format while preserving the advantages conferred by high shattering dimensionality.

The Anatomy and Physiology of Claustrum-Cortex Interactions.

The claustrum is one of the most widely connected regions of the forebrain, yet its function has remained obscure, largely due to the experimentally challenging nature of targeting this small, thin, and elongated brain area. However, recent advances in molecular techniques have enabled the anatomy and physiology of the claustrum to be studied with the spatiotemporal and cell type-specific precision required to eventually converge on what this area does. Here we review early anatomical and electrophysiological results from cats and primates, as well as recent work in the rodent, identifying the connectivity, cell types, and physiological circuit mechanisms underlying the communication between the claustrum and the cortex. The emerging picture is one in which the rodent claustrum is closely tied to frontal/limbic regions and plays a role in processes, such as attention, that are associated with these areas.

Regulation of prefrontal patterning and connectivity by retinoic acid.

The prefrontal cortex (PFC) and its connections with the mediodorsal thalamus are crucial for cognitive flexibility and working memory1 and are thought to be altered in disorders such as autism2,3 and schizophrenia4,5. Although developmental mechanisms that govern the regional patterning of the cerebral cortex have been characterized in rodents6-9, the mechanisms that underlie the development of PFC-mediodorsal thalamus connectivity and the lateral expansion of the PFC with a distinct granular layer 4 in primates10,11 remain unknown. Here we report an anterior (frontal) to posterior (temporal), PFC-enriched gradient of retinoic acid, a signalling molecule that regulates neural development and function12-15, and we identify genes that are regulated by retinoic acid in the neocortex of humans and macaques at the early and middle stages of fetal development. We observed several potential sources of retinoic acid, including the expression and cortical expansion of retinoic-acid-synthesizing enzymes specifically in primates as compared to mice. Furthermore, retinoic acid signalling is largely confined to the prospective PFC by CYP26B1, a retinoic-acid-catabolizing enzyme, which is upregulated in the prospective motor cortex. Genetic deletions in mice revealed that retinoic acid signalling through the retinoic acid receptors RXRG and RARB, as well as CYP26B1-dependent catabolism, are involved in proper molecular patterning of prefrontal and motor areas, development of PFC-mediodorsal thalamus connectivity, intra-PFC dendritic spinogenesis and expression of the layer 4 marker RORB. Together, these findings show that retinoic acid signalling has a critical role in the development of the PFC and, potentially, in its evolutionary expansion.

Frontal cortex neuron types categorically encode single decision variables.

Individual neurons in many cortical regions have been found to encode specific, identifiable features of the environment or body that pertain to the function of the region1-3. However, in frontal cortex, which is involved in cognition, neural responses display baffling complexity, carrying seemingly disordered mixtures of sensory, motor and other task-related variables4-13. This complexity has led to the suggestion that representations in individual frontal neurons are randomly mixed and can only be understood at the neural population level14,15. Here we show that neural activity in rat orbitofrontal cortex (OFC) is instead highly structured: single neuron activity co-varies with individual variables in computational models that explain choice behaviour. To characterize neural responses across a large behavioural space, we trained rats on a behavioural task that combines perceptual and value-guided decisions. An unbiased, model-free clustering analysis identified distinct groups of OFC neurons, each with a particular response profile in task-variable space. Applying a simple model of choice behaviour to these categorical response profiles revealed that each profile quantitatively corresponds to a specific decision variable, such as decision confidence. Additionally, we demonstrate that a connectivity-defined cell type, orbitofrontal neurons projecting to the striatum, carries a selective and temporally sustained representation of a single decision variable: integrated value. We propose that neurons in frontal cortex, as in other cortical regions, form a sparse and overcomplete representation of features relevant to the region's function, and that they distribute this information selectively to downstream regions to support behaviour.

Neuropil Variation in the Prefrontal, Motor, and Visual Cortex of Six Felids.

INTRODUCTION: Felids have evolved a specialized suite of morphological adaptations for obligate carnivory. Although the musculoskeletal anatomy of the Felidae has been studied extensively, the comparative neuroanatomy of felids is relatively unexplored. Little is known about how variation in the cerebral anatomy of felids relates to species-specific differences in sociality, hunting strategy, or activity patterns. METHODS: We quantitatively analyzed neuropil variation in the prefrontal, primary motor, and primary visual cortices of six species of Felidae (Panthera leo, Panthera uncia, Panthera tigris, Panthera leopardus, Acinonyx jubatus, Felis sylvestris domesticus) to investigate relationships with brain size, neuronal cell parameters, and select behavioral and ecological factors. Neuropil is the dense, intricate network of axons, dendrites, and synapses in the brain, playing a critical role in information processing and communication between neurons. RESULTS: There were significant species and regional differences in neuropil proportions, with African lion, cheetah, and tiger having more neuropil in all three cortical regions in comparison to the other species. Based on regression analyses, we find that the increased neuropil fraction in the prefrontal cortex supports social and behavioral flexibility, while in the primary motor cortex, this facilitates the neural activity needed for hunting movements. Greater neuropil fraction in the primary visual cortex may contribute to visual requirements associated with diel activity patterns. CONCLUSION: These results provide a cross-species comparison of neuropil fraction variation in the Felidae, particularly the understudied Panthera, and provide evidence for convergence of the neuroanatomy of Panthera and cheetahs.

General cortical and special prefrontal connections: principles from structure to function.

How is the vast brain communication system organized? A structural model relates connections to laminar differences between linked areas. The model is based on the principle of systematic structural variation in the cortex, extending from the simplest limbic cortices to eulaminate areas with elaborate lamination. The model accounts for laminar patterns and for the strength and topography of connections between nearby or distant cortices and subcortical structures, exemplified quantitatively for the principal and special prefrontal connections. Widespread connections of limbic areas and focal connections of eulaminate areas yield a broad range of circuit patterns for diverse functions. These diverse pathways innervate excitatory and functionally distinct inhibitory neurons, providing the basis for differential recruitment of areas for flexible behavior. Systematic structural variation likely emerges by timing differences in the development of distinct areas and has important implications for altered connections in diseases of developmental origin.

Longitudinal changes in DLPFC activation during childhood are related to decreased aggression following social rejection.

Regulating aggression after social feedback is an important prerequisite for developing and maintaining social relations, especially in the current times with larger emphasis on online social evaluation. Studies in adults highlighted the role of the dorsolateral prefrontal cortex (DLPFC) in regulating aggression. Little is known about the development of aggression regulation following social feedback during childhood, while this is an important period for both brain maturation and social relations. The current study used a longitudinal design, with 456 twins undergoing two functional MRI sessions across the transition from middle (7 to 9 y) to late (9 to 11 y) childhood. Aggression regulation was studied using the Social Network Aggression Task. Behavioral aggression after social evaluation decreased over time, whereas activation in the insula, dorsomedial PFC and DLPFC increased over time. Brain-behavior analyses showed that increased DLPFC activation after negative feedback was associated with decreased aggression. Change analyses further revealed that children with larger increases in DLPFC activity from middle to late childhood showed stronger decreases in aggression over time. These findings provide insights into the development of social evaluation sensitivity and aggression control in childhood.

Imaging local genetic influences on cortical folding.

Recent progress in deciphering mechanisms of human brain cortical folding leave unexplained whether spatially patterned genetic influences contribute to this folding. High-resolution in vivo brain MRI can be used to estimate genetic correlations (covariability due to shared genetic factors) in interregional cortical thickness, and biomechanical studies predict an influence of cortical thickness on folding patterns. However, progress has been hampered because shared genetic influences related to folding patterns likely operate at a scale that is much more local (<1 cm) than that addressed in prior imaging studies. Here, we develop methodological approaches to examine local genetic influences on cortical thickness and apply these methods to two large, independent samples. We find that such influences are markedly heterogeneous in strength, and in some cortical areas are notably stronger in specific orientations relative to gyri or sulci. The overall, phenotypic local correlation has a significant basis in shared genetic factors and is highly symmetric between left and right cortical hemispheres. Furthermore, the degree of local cortical folding relates systematically with the strength of local correlations, which tends to be higher in gyral crests and lower in sulcal fundi. The relationship between folding and local correlations is stronger in primary sensorimotor areas and weaker in association areas such as prefrontal cortex, consistent with reduced genetic constraints on the structural topology of association cortex. Collectively, our results suggest that patterned genetic influences on cortical thickness, measurable at the scale of in vivo MRI, may be a causal factor in the development of cortical folding.

Divergence of rodent and primate medial frontal cortex functional connectivity.

With the medial frontal cortex (MFC) centrally implicated in several major neuropsychiatric disorders, it is critical to understand the extent to which MFC organization is comparable between humans and animals commonly used in preclinical research (namely rodents and nonhuman primates). Although the cytoarchitectonic structure of the rodent MFC has mostly been conserved in humans, it is a long-standing question whether the structural analogies translate to functional analogies. Here, we probed this question using ultra high field fMRI data to compare rat, marmoset, and human MFC functional connectivity. First, we applied hierarchical clustering to intrinsically define the functional boundaries of the MFC in all three species, independent of cytoarchitectonic definitions. Then, we mapped the functional connectivity "fingerprints" of these regions with a number of different brain areas. Because rats do not share cytoarchitectonically defined regions of the lateral frontal cortex (LFC) with primates, the fingerprinting method also afforded the unique ability to compare the rat MFC and marmoset LFC, which have often been suggested to be functional analogs. The results demonstrated remarkably similar intrinsic functional organization of the MFC across the species, but clear differences between rodent and primate MFC whole-brain connectivity. Rat MFC patterns of connectivity showed greatest similarity with premotor regions in the marmoset, rather than dorsolateral prefrontal regions, which are often suggested to be functionally comparable. These results corroborate the viability of the marmoset as a preclinical model of human MFC dysfunction, and suggest divergence of functional connectivity between rats and primates in both the MFC and LFC.

Overlooked Tertiary Sulci Serve as a Meso-Scale Link between Microstructural and Functional Properties of Human Lateral Prefrontal Cortex.

Understanding the relationship between neuroanatomy and function in portions of cortex that perform functions largely specific to humans such as lateral prefrontal cortex (LPFC) is of major interest in systems and cognitive neuroscience. When considering neuroanatomical-functional relationships in LPFC, shallow indentations in cortex known as tertiary sulci have been largely unexplored. Here, by implementing a multimodal approach and manually defining 936 neuroanatomical structures in 72 hemispheres (in both males and females), we show that a subset of these overlooked tertiary sulci serve as a meso-scale link between microstructural (myelin content) and functional (network connectivity) properties of human LPFC in individual participants. For example, the posterior middle frontal sulcus (pmfs) is a tertiary sulcus with three components that differ in their myelin content, resting-state connectivity profiles, and engagement across meta-analyses of 83 cognitive tasks. Further, generating microstructural profiles of myelin content across cortical depths for each pmfs component and the surrounding middle frontal gyrus (MFG) shows that both gyral and sulcal components of the MFG have greater myelin content in deeper compared with superficial layers and that the myelin content in superficial layers of the gyral components is greater than sulcal components. These findings support a classic, yet largely unconsidered theory that tertiary sulci may serve as landmarks in association cortices, as well as a modern cognitive neuroscience theory proposing a functional hierarchy in LPFC. As there is a growing need for computational tools that automatically define tertiary sulci throughout cortex, we share pmfs probabilistic sulcal maps with the field.SIGNIFICANCE STATEMENT Lateral prefrontal cortex (LPFC) is critical for functions that are thought to be specific to humans compared with other mammals. However, relationships between fine-scale neuroanatomical structures largely specific to hominoid cortex and functional properties of LPFC remain elusive. Here, we show that these structures, which have been largely unexplored throughout history, surprisingly serve as markers for anatomical and functional organization in human LPFC. These findings have theoretical, methodological, developmental, and evolutionary implications for improved understanding of neuroanatomical-functional relationships not only in LPFC, but also in association cortices more broadly. Finally, these findings ignite new questions regarding how morphological features of these neglected neuroanatomical structures contribute to functions of association cortices that are critical for human-specific aspects of cognition.

Prefronto-Striatal Structural Connectivity Mediates Adult Age Differences in Action Selection.

In complex everyday environments, action selection is critical for optimal goal-directed behavior. This refers to the process of choosing a proper action from the range of possible alternatives. The neural mechanisms underlying action selection and how these are affected by normal aging remain to be elucidated. In the present cross-sectional study, we studied processes of effector selection during a multilimb reaction time task in a lifespan sample of healthy human adults (N = 89; 20-75 years; 48 males, 41 females). Participants were instructed to react as quickly and accurately as possible to visually cued stimuli representing single-limb or combined upper and/or lower limb motions. Diffusion MRI was used to study structural connectivity between prefrontal and striatal regions as critical nodes for action selection. Behavioral findings revealed that increasing age was associated with slowing of action selection performance. At the neural level, aging had a negative impact on prefronto-striatal connectivity. Importantly, mediation analyses revealed that the negative association between action selection performance and age was mediated by prefronto-striatal connectivity, specifically the connections between left rostral medial frontal gyrus and left nucleus accumbens as well as right frontal pole and left caudate. These results highlight the potential role of prefronto-striatal white matter decline in poorer action selection performance of older adults.SIGNIFICANCE STATEMENT As a result of enhanced life expectancy, researchers have devoted increasing attention to the study of age-related alterations in cognitive and motor functions. Here we study associations between brain structure and behavior to reveal the impact of central neural white matter changes as a function of normal aging on action selection performance. We demonstrate the critical role of a reduction in prefronto-striatal structural connectivity in accounting for action selection performance deficits in healthy older adults. Preserving this cortico-subcortical pathway may be critical for behavioral flexibility and functional independence in older age.

Polygenic risk score for bipolar disorder associates with divergent thinking and brain structures in the prefrontal cortex.

It has been hypothesized that a higher genetic risk of bipolar disorder (BD) is associated with greater creativity. Given the clinical importance of bipolar disorder and the importance of creativity to human society and cultural development, it is essential to reveal their associations and the neural basis of the genetic risk of bipolar disorder to gain insight into its etiology. However, despite the previous demonstration of the associations of polygenic risk score (PRS) of BD and creative jobs, the associations of BD-PRS and creativity measured by the divergent thinking (CMDT) and regional gray matter volume (rGMV) as well as regional white matter volume (rWMV) have not been investigated. Using psychological analyses and whole-brain voxel-by-voxel analyses, we examined these potential associations in 1558 young, typically developing adult students. After adjusting for confounding variables and multiple comparisons, a greater BD-PRS was associated with a greater total CMDT fluency score, and a significant relationship was found in fluency subscores. A greater BD-PRS was also associated with lower total mood disturbance. Neuroimaging analyses revealed that the BD-PRS was associated with greater rGMV in the right inferior frontal gyrus, which is a consistently affected area in BD, as well as a greater rWMV in the left middle frontal gyrus, which has been suggested to play a central role in the increased creativity associated with the risk of BD with creativity. These findings suggest a relationship between the genetic risk of BD and CMDT and prefrontal cortical structures among young educated individuals.

Differential spatial patterns of structural connectivity of amygdala nuclei with orbitofrontal cortex.

The orbitofrontal cortex (OFC)-amygdala circuit is critical to goal-directed behavior, learning, and valuation. However, our understanding of the OFC-amygdala connections that support these emergent processes is hampered by our reliance on the primate literature and insufficient knowledge regarding the connectivity patterns between regions of OFC and amygdala nuclei, each of which is differentially involved in these processes in humans. Thus, we examined structural connectivity between different OFC regions and four amygdala nuclei in healthy adults (n = 1,053) using diffusion-based anatomical networks and probabilistic tractography in four conceptually distinct ways. First, we identified the OFC regions that connect with each nucleus. Second, we identified the OFC regions that were more likely to connect with a given nucleus than the others. Finally, we developed probabilistic and rank-order maps of OFC (one for each nucleus) based upon the likelihood of each OFC voxel exhibiting preferential connectivity with each nucleus and the relative density of connectivity between each OFC voxel and each nucleus, respectively. The first analyses revealed that the connections of each nucleus spanned all of OFC, reflecting widespread overall amygdala linkage with OFC. Analysis of preferential connectivity and probabilistic and rank-order maps of OFC converged to reveal differential patterns of connectivity between OFC and each nucleus. Present findings illustrate the importance of accounting for spatial specificity when examining links between OFC and amygdala. This fine-grained examination of OFC-amygdala connectivity can be applied to understand how such connectivity patterns support a range of emergent functions including affective and motivational processes.

Regional gray matter volume associated with exercise dependence: A voxel-based morphometry study.

Although regular physical exercise has multiple positive benefits for the general population, excessive exercise may lead to exercise dependence (EXD), which is harmful to one's physical and mental health. Increasing evidence suggests that stress is a potential risk factor for the onset and development of EXD. However, little is known about the neural substrates of EXD and the underlying neuropsychological mechanism by which stress affects EXD. Herein, we investigate these issues in 86 individuals who exercise regularly by estimating their cortical gray matter volume (GMV) utilizing a voxel-based morphometry method based on structural magnetic resonance imaging. Whole-brain correlation analyses and prediction analyses showed negative relationships between EXD and GMV of the right orbitofrontal cortex (OFC), left subgenual cingulate gyrus (sgCG), and left inferior parietal lobe (IPL). Furthermore, mediation analyses found that the GMV of the right OFC was an important mediator between stress and EXD. Importantly, these results remained significant even when adjusting for sex, age, body mass index, family socioeconomic status, general intelligence and total intracranial volume, as well as depression and anxiety. Collectively, the results of the present study provide crucial evidence of the neuroanatomical basis of EXD and reveal a potential neuropsychological pathway in predicting EXD in which GMV mediates the relationship between stress and EXD.

Variability of white matter anatomy in the subcallosal cingulate area.

The subcallosal cingulate (SCC) area is a putative hub in the brain network underlying depression. Deep brain stimulation (DBS) targeting a particular subregion of SCC, identified as the intersection of forceps minor (FM), uncinate fasciculus (UCF), cingulum and fronto-striatal fiber bundles, may be critical to a therapeutic response in patients with severe, treatment-resistant forms of major depressive disorder (MDD). The pattern and variability of the white matter anatomy and organization within SCC has not been extensively characterized across individuals. The goal of this study is to investigate the variability of white matter bundles within the SCC that structurally connect this region with critical nodes in the depression network. Structural and diffusion data from 100 healthy subjects from the Human Connectome Project database were analyzed. Anatomically defined SCC regions were used as seeds to perform probabilistic tractography and to estimate the connectivity from the SCC to subject-specific target areas believed to be involved in the pathology of MDD including ventral striatum (VS), UCF, anterior cingulate cortex (ACC), and medial prefrontal cortex (mPFC). Four distinct areas of connectivity were identified within SCC across subjects: (a) postero-lateral SCC connectivity to medial temporal regions via UCF, (b) postero-medial connectivity to VS, (c) superior-medial connectivity to ACC via cingulum bundle, and (d) antero-lateral connectivity to mPFC regions via forceps minor. Assuming white matter connectivity is critical to therapeutic response, the improved anatomic understanding of SCC as well as an appreciation of the intersubject variability are critical to developing optimized therapeutic targeting for SCC DBS.

The neural system of metacognition accompanying decision-making in the prefrontal cortex.

Decision-making is usually accompanied by metacognition, through which a decision maker monitors uncertainty regarding a decision and may then consequently revise the decision. These metacognitive processes can occur prior to or in the absence of feedback. However, the neural mechanisms of metacognition remain controversial. One theory proposes an independent neural system for metacognition in the prefrontal cortex (PFC); the other, that metacognitive processes coincide and overlap with the systems used for the decision-making process per se. In this study, we devised a novel "decision-redecision" paradigm to investigate the neural metacognitive processes involved in redecision as compared to the initial decision-making process. The participants underwent a perceptual decision-making task and a rule-based decision-making task during functional magnetic resonance imaging (fMRI). We found that the anterior PFC, including the dorsal anterior cingulate cortex (dACC) and lateral frontopolar cortex (lFPC), were more extensively activated after the initial decision. The dACC activity in redecision positively scaled with decision uncertainty and correlated with individual metacognitive uncertainty monitoring abilities-commonly occurring in both tasks-indicating that the dACC was specifically involved in decision uncertainty monitoring. In contrast, the lFPC activity seen in redecision processing was scaled with decision uncertainty reduction and correlated with individual accuracy changes-positively in the rule-based decision-making task and negatively in the perceptual decision-making task. Our results show that the lFPC was specifically involved in metacognitive control of decision adjustment and was subject to different control demands of the tasks. Therefore, our findings support that a separate neural system in the PFC is essentially involved in metacognition and further, that functions of the PFC in metacognition are dissociable.

Threat-anticipatory psychophysiological response is enhanced in youth with anxiety disorders and correlates with prefrontal cortex neuroanatomy.

Background: Threat anticipation engages neural circuitry that has evolved to promote defensive behaviours; perturbations in this circuitry could generate excessive threat-anticipation response, a key characteristic of pathological anxiety. Research into such mechanisms in youth faces ethical and practical limitations. Here, we use thermal stimulation to elicit pain-anticipatory psychophysiological response and map its correlates to brain structure among youth with anxiety and healthy youth. Methods: Youth with anxiety (n = 25) and healthy youth (n = 25) completed an instructed threat-anticipation task in which cues predicted nonpainful or painful thermal stimulation; we indexed psychophysiological response during the anticipation and experience of pain using skin conductance response. High-resolution brain-structure imaging data collected in another visit were available for 41 participants. Analyses tested whether the 2 groups differed in their psychophysiological cue-based pain-anticipatory and pain-experience responses. Analyses then mapped psychophysiological response magnitude to brain structure. Results: Youth with anxiety showed enhanced psychophysiological response specifically during anticipation of painful stimulation (b = 0.52, p = 0.003). Across the sample, the magnitude of psychophysiological anticipatory response correlated negatively with the thickness of the dorsolateral prefrontal cortex (pFWE < 0.05); psychophysiological response to the thermal stimulation correlated positively with the thickness of the posterior insula (pFWE < 0.05). Limitations: Limitations included the modest sample size and the cross-sectional design. Conclusion: These findings show that threat-anticipatory psychophysiological response differentiates youth with anxiety from healthy youth, and they link brain structure to psychophysiological response during pain anticipation and experience. A focus on threat anticipation in research on anxiety could delineate relevant neural circuitry.

Connections of the Human Orbitofrontal Cortex and Inferior Frontal Gyrus.

The direct connections of the orbitofrontal cortex (OFC) were traced with diffusion tractography imaging and statistical analysis in 50 humans, to help understand better its roles in emotion and its disorders. The medial OFC and ventromedial prefrontal cortex have direct connections with the pregenual and subgenual parts of the anterior cingulate cortex; all of which are reward-related areas. The lateral OFC (OFClat) and its closely connected right inferior frontal gyrus (rIFG) have direct connections with the supracallosal anterior cingulate cortex; all of which are punishment or nonreward-related areas. The OFClat and rIFG also have direct connections with the right supramarginal gyrus and inferior parietal cortex, and with some premotor cortical areas, which may provide outputs for the OFClat and rIFG. Another key finding is that the ventromedial prefrontal cortex shares with the medial OFC especially strong outputs to the nucleus accumbens and olfactory tubercle, which comprise the ventral striatum, whereas the other regions have more widespread outputs to the striatum. Direct connections of the OFC and IFG were with especially the temporal pole part of the temporal lobe. The left IFG, which includes Broca's area, has direct connections with the left angular and supramarginal gyri.

The Graded Change in Connectivity across the Ventromedial Prefrontal Cortex Reveals Distinct Subregions.

The functional heterogeneity of the ventromedial prefrontal cortex (vmPFC) suggests it may include distinct functional subregions. To date these have not been well elucidated. Regions with differentiable connectivity (and as a result likely dissociable functions) may be identified using emergent data-driven approaches. However, prior parcellations of the vmPFC have only considered hard splits between distinct regions, although both hard and graded connectivity changes may exist. Here we determine the full pattern of change in structural and functional connectivity across the vmPFC for the first time and extract core distinct regions. Both structural and functional connectivity varied along a dorsomedial to ventrolateral axis from relatively dorsal medial wall regions to relatively lateral basal orbitofrontal cortex. The pattern of connectivity shifted from default mode network to sensorimotor and multimodal semantic connections. This finding extends the classical distinction between primate medial and orbital regions by demonstrating a similar gradient in humans for the first time. Additionally, core distinct regions in the medial wall and orbitofrontal cortex were identified that may show greater correspondence to functional differences than prior hard parcellations. The possible functional roles of the orbitofrontal cortex and medial wall are discussed.

Corticostriatal White Matter Integrity and Dopamine D1 Receptor Availability Predict Age Differences in Prefrontal Value Signaling during Reward Learning.

Probabilistic reward learning reflects the ability to adapt choices based on probabilistic feedback. The dopaminergically innervated corticostriatal circuit in the brain plays an important role in supporting successful probabilistic reward learning. Several components of the corticostriatal circuit deteriorate with age, as it does probabilistic reward learning. We showed previously that D1 receptor availability in NAcc predicts the strength of anticipatory value signaling in vmPFC, a neural correlate of probabilistic learning that is attenuated in older participants and predicts probabilistic reward learning performance. We investigated how white matter integrity in the pathway between nucleus accumbens (NAcc) and ventromedial prefrontal cortex (vmPFC) relates to the strength of anticipatory value signaling in vmPFC in younger and older participants. We found that in a sample of 22 old and 23 young participants, fractional anisotropy in the pathway between NAcc and vmPFC predicted the strength of value signaling in vmPFC independently from D1 receptor availability in NAcc. These findings provide tentative evidence that integrity in the dopaminergic and white matter pathways of corticostriatal circuitry supports the expression of value signaling in vmPFC which supports reward learning, however, the limited sample size calls for independent replication. These and future findings could add to the improved understanding of how corticostriatal integrity contributes to reward learning ability.