Understanding the neural basis of natural intelligence.

Understanding the neural basis of natural intelligence necessitates a paradigm shift: from strict reductionism toward embracing complexity and diversity. New tools and theories enable us to tackle this challenge, providing unprecedented access to neural dynamics and behavior across time, contexts, and species. Principles for intelligent behavior and learning in the natural world are now, more than ever, within reach.

APC7 mediates ubiquitin signaling in constitutive heterochromatin in the developing mammalian brain.

Neurodevelopmental cognitive disorders provide insights into mechanisms of human brain development. Here, we report an intellectual disability syndrome caused by the loss of APC7, a core component of the E3 ubiquitin ligase anaphase promoting complex (APC). In mechanistic studies, we uncover a critical role for APC7 during the recruitment and ubiquitination of APC substrates. In proteomics analyses of the brain from mice harboring the patient-specific APC7 mutation, we identify the chromatin-associated protein Ki-67 as an APC7-dependent substrate of the APC in neurons. Conditional knockout of the APC coactivator protein Cdh1, but not Cdc20, leads to the accumulation of Ki-67 protein in neurons in vivo, suggesting that APC7 is required for the function of Cdh1-APC in the brain. Deregulated neuronal Ki-67 upon APC7 loss localizes predominantly to constitutive heterochromatin. Our findings define an essential function for APC7 and Cdh1-APC in neuronal heterochromatin regulation, with implications for understanding human brain development and disease.

Expertise increases planning depth in human gameplay.

A hallmark of human intelligence is the ability to plan multiple steps into the future1,2. Despite decades of research3-5, it is still debated whether skilled decision-makers plan more steps ahead than novices6-8. Traditionally, the study of expertise in planning has used board games such as chess, but the complexity of these games poses a barrier to quantitative estimates of planning depth. Conversely, common planning tasks in cognitive science often have a lower complexity9,10 and impose a ceiling for the depth to which any player can plan. Here we investigate expertise in a complex board game that offers ample opportunity for skilled players to plan deeply. We use model fitting methods to show that human behaviour can be captured using a computational cognitive model based on heuristic search. To validate this model, we predict human choices, response times and eye movements. We also perform a Turing test and a reconstruction experiment. Using the model, we find robust evidence for increased planning depth with expertise in both laboratory and large-scale mobile data. Experts memorize and reconstruct board features more accurately. Using complex tasks combined with precise behavioural modelling might expand our understanding of human planning and help to bridge the gap with progress in artificial intelligence.

Sleep Spindles: Mechanisms and Functions.

Sleep spindles are burstlike signals in the electroencephalogram (EEG) of the sleeping mammalian brain and electrical surface correlates of neuronal oscillations in thalamus. As one of the most inheritable sleep EEG signatures, sleep spindles probably reflect the strength and malleability of thalamocortical circuits that underlie individual cognitive profiles. We review the characteristics, organization, regulation, and origins of sleep spindles and their implication in non-rapid-eye-movement sleep (NREMS) and its functions, focusing on human and rodent. Spatially, sleep spindle-related neuronal activity appears on scales ranging from small thalamic circuits to functional cortical areas, and generates a cortical state favoring intracortical plasticity while limiting cortical output. Temporally, sleep spindles are discrete events, part of a continuous power band, and elements grouped on an infraslow time scale over which NREMS alternates between continuity and fragility. We synthesize diverse and seemingly unlinked functions of sleep spindles for sleep architecture, sensory processing, synaptic plasticity, memory formation, and cognitive abilities into a unifying sleep spindle concept, according to which sleep spindles 1) generate neural conditions of large-scale functional connectivity and plasticity that outlast their appearance as discrete EEG events, 2) appear preferentially in thalamic circuits engaged in learning and attention-based experience during wakefulness, and 3) enable a selective reactivation and routing of wake-instated neuronal traces between brain areas such as hippocampus and cortex. Their fine spatiotemporal organization reflects NREMS as a physiological state coordinated over brain and body and may indicate, if not anticipate and ultimately differentiate, pathologies in sleep and neurodevelopmental, -degenerative, and -psychiatric conditions.

Genome-wide detection of tandem DNA repeats that are expanded in autism.

Tandem DNA repeats vary in the size and sequence of each unit (motif). When expanded, these tandem DNA repeats have been associated with more than 40 monogenic disorders1. Their involvement in disorders with complex genetics is largely unknown, as is the extent of their heterogeneity. Here we investigated the genome-wide characteristics of tandem repeats that had motifs with a length of 2-20 base pairs in 17,231 genomes of families containing individuals with autism spectrum disorder (ASD)2,3 and population control individuals4. We found extensive polymorphism in the size and sequence of motifs. Many of the tandem repeat loci that we detected correlated with cytogenetic fragile sites. At 2,588 loci, gene-associated expansions of tandem repeats that were rare among population control individuals were significantly more prevalent among individuals with ASD than their siblings without ASD, particularly in exons and near splice junctions, and in genes related to the development of the nervous system and cardiovascular system or muscle. Rare tandem repeat expansions had a prevalence of 23.3% in children with ASD compared with 20.7% in children without ASD, which suggests that tandem repeat expansions make a collective contribution to the risk of ASD of 2.6%. These rare tandem repeat expansions included previously undescribed ASD-linked expansions in DMPK and FXN, which are associated with neuromuscular conditions, and in previously unknown loci such as FGF14 and CACNB1. Rare tandem repeat expansions were associated with lower IQ and adaptive ability. Our results show that tandem DNA repeat expansions contribute strongly to the genetic aetiology and phenotypic complexity of ASD.

Automating hybrid collective intelligence in open-ended medical diagnostics.

Collective intelligence has emerged as a powerful mechanism to boost decision accuracy across many domains, such as geopolitical forecasting, investment, and medical diagnostics. However, collective intelligence has been mostly applied to relatively simple decision tasks (e.g., binary classifications). Applications in more open-ended tasks with a much larger problem space, such as emergency management or general medical diagnostics, are largely lacking, due to the challenge of integrating unstandardized inputs from different crowd members. Here, we present a fully automated approach for harnessing collective intelligence in the domain of general medical diagnostics. Our approach leverages semantic knowledge graphs, natural language processing, and the SNOMED CT medical ontology to overcome a major hurdle to collective intelligence in open-ended medical diagnostics, namely to identify the intended diagnosis from unstructured text. We tested our method on 1,333 medical cases diagnosed on a medical crowdsourcing platform: The Human Diagnosis Project. Each case was independently rated by ten diagnosticians. Comparing the diagnostic accuracy of single diagnosticians with the collective diagnosis of differently sized groups, we find that our method substantially increases diagnostic accuracy: While single diagnosticians achieved 46% accuracy, pooling the decisions of ten diagnosticians increased this to 76%. Improvements occurred across medical specialties, chief complaints, and diagnosticians' tenure levels. Our results show the life-saving potential of tapping into the collective intelligence of the global medical community to reduce diagnostic errors and increase patient safety.

Incentivizing free riders improves collective intelligence in social dilemmas.

Collective intelligence challenges are often entangled with collective action problems. For example, voting, rating, and social innovation are collective intelligence tasks that require costly individual contributions. As a result, members of a group often free ride on the information contributed by intrinsically motivated people. Are intrinsically motivated agents the best participants in collective decisions? We embedded a collective intelligence task in a large-scale, virtual world public good game and found that participants who joined the information system but were reluctant to contribute to the public good (free riders) provided more accurate evaluations, whereas participants who rated frequently underperformed. Testing the underlying mechanism revealed that a negative rating bias in free riders is associated with higher accuracy. Importantly, incentivizing evaluations amplifies the relative influence of participants who tend to free ride without altering the (higher) quality of their evaluations, thereby improving collective intelligence. These results suggest that many of the currently available information systems, which strongly select for intrinsically motivated participants, underperform and that collective intelligence can benefit from incentivizing free riding members to engage. More generally, enhancing the diversity of contributor motivations can improve collective intelligence in settings that are entangled with collective action problems.

Neonatal Docosahexaenoic Acid in Preterm Infants and Intelligence at 5 Years.

BACKGROUND: Docosahexaenoic acid (DHA) is a component of neural tissue. Because its accretion into the brain is greatest during the final trimester of pregnancy, infants born before 29 weeks' gestation do not receive the normal supply of DHA. The effect of this deficiency on subsequent cognitive development is not well understood. METHODS: We assessed general intelligence at 5 years in children who had been enrolled in a trial of neonatal DHA supplementation to prevent bronchopulmonary dysplasia. In the previous trial, infants born before 29 weeks' gestation had been randomly assigned in a 1:1 ratio to receive an enteral emulsion that provided 60 mg of DHA per kilogram of body weight per day or a control emulsion from the first 3 days of enteral feeds until 36 weeks of postmenstrual age or discharge home, whichever occurred first. Children from 5 of the 13 centers in the original trial were invited to undergo assessment with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) at 5 years of corrected age. The primary outcome was the full-scale intelligence quotient (FSIQ) score. Secondary outcomes included the components of WPPSI. RESULTS: A total of 1273 infants underwent randomization in the original trial; of the 656 surviving children who had undergone randomization at the centers included in this follow-up study, 480 (73%) had an FSIQ score available - 241 in the DHA group and 239 in the control group. After imputation of missing data, the mean (±SD) FSIQ scores were 95.4±17.3 in the DHA group and 91.9±19.1 in the control group (adjusted difference, 3.45; 95% confidence interval, 0.38 to 6.53; P = 0.03). The results for secondary outcomes generally did not support that obtained for the primary outcome. Adverse events were similar in the two groups. CONCLUSIONS: In infants born before 29 weeks' gestation who had been enrolled in a trial to assess the effect of DHA supplementation on bronchopulmonary dysplasia, the use of an enteral DHA emulsion until 36 weeks of postmenstrual age was associated with modestly higher FSIQ scores at 5 years of age than control feeding. (Funded by the Australian National Health and Medical Research Council and Nu-Mega Ingredients; N3RO Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820.).

The Moral Psychology of Artificial Intelligence.

Moral psychology was shaped around three categories of agents and patients: humans, other animals, and supernatural beings. Rapid progress in artificial intelligence has introduced a fourth category for our moral psychology to deal with: intelligent machines. Machines can perform as moral agents, making decisions that affect the outcomes of human patients or solving moral dilemmas without human supervision. Machines can be perceived as moral patients, whose outcomes can be affected by human decisions, with important consequences for human-machine cooperation. Machines can be moral proxies that human agents and patients send as their delegates to moral interactions or use as a disguise in these interactions. Here we review the experimental literature on machines as moral agents, moral patients, and moral proxies, with a focus on recent findings and the open questions that they suggest.

Twisting for soft intelligent autonomous robot in unstructured environments.

Soft robots that can harvest energy from environmental resources for autonomous locomotion is highly desired; however, few are capable of adaptive navigation without human interventions. Here, we report twisting soft robots with embodied physical intelligence for adaptive, intelligent autonomous locomotion in various unstructured environments, without on-board or external controls and human interventions. The soft robots are constructed of twisted thermal-responsive liquid crystal elastomer ribbons with a straight centerline. They can harvest thermal energy from environments to roll on outdoor hard surfaces and challenging granular substrates without slip, including ascending loose sandy slopes, crossing sand ripples, escaping from burying sand, and crossing rocks with additional camouflaging features. The twisting body provides anchoring functionality by burrowing into loose sand. When encountering obstacles, they can either self-turn or self-snap for obstacle negotiation and avoidance. Theoretical models and finite element simulation reveal that such physical intelligence is achieved by spontaneously snapping-through its soft body upon active and adaptive soft body-obstacle interactions. Utilizing this strategy, they can intelligently escape from confined spaces and maze-like obstacle courses without any human intervention. This work presents a de novo design of embodied physical intelligence by harnessing the twisting geometry and snap-through instability for adaptive soft robot-environment interactions.

Comparing the reliability and predictive power of child, teacher, and guardian reports of noncognitive skills.

Children's noncognitive or socioemotional skills (e.g., persistence and self-control) are typically measured using surveys in which either children rate their own skills or adults rate the skills of children. For many purposes-including program evaluation and monitoring school systems-ratings are often collected from multiple perspectives about a single child (e.g., from both the child and an adult). Collecting data from multiple perspectives is costly, and there is limited evidence on the benefits of this approach. Using a longitudinal survey, this study compares children's noncognitive skills as reported by themselves, their guardians, and their teachers. Although reports from all three types of respondents are correlated with each other, teacher reports have the highest internal consistency and are the most predictive of children's later cognitive outcomes and behavior in school. The teacher reports add predictive power beyond baseline measures of Intelligence Quotient (IQ) for most outcomes in schools. Measures collected from children and guardians add minimal predictive power beyond the teacher reports.

Signatures of adaptive evolution in platyrrhine primate genomes.

The platyrrhine family Cebidae (capuchin and squirrel monkeys) exhibit among the largest primate encephalization quotients. Each cebid lineage is also characterized by notable lineage-specific traits, with capuchins showing striking similarities to Hominidae such as high sensorimotor intelligence with tool use, advanced cognitive abilities, and behavioral flexibility. Here, we take a comparative genomics approach, performing genome-wide tests for positive selection across five cebid branches, to gain insight into major periods of cebid adaptive evolution. We uncover candidate targets of selection across cebid evolutionary history that may underlie the emergence of lineage-specific traits. Our analyses highlight shifting and sustained selective pressures on genes related to brain development, longevity, reproduction, and morphology, including evidence for cumulative and diversifying neurobiological adaptations across cebid evolution. In addition to generating a high-quality reference genome assembly for robust capuchins, our results lend to a better understanding of the adaptive diversification of this distinctive primate clade.

Neural Contributions to Reduced Fluid Intelligence across the Adult Lifespan.

Fluid intelligence, the ability to solve novel, complex problems, declines steeply during healthy human aging. Using fMRI, fluid intelligence has been repeatedly associated with activation of a frontoparietal brain network, and impairment following focal damage to these regions suggests that fluid intelligence depends on their integrity. It is therefore possible that age-related functional differences in frontoparietal activity contribute to the reduction in fluid intelligence. This paper reports on analysis of the Cambridge Center for Ageing and Neuroscience data, a large, population-based cohort of healthy males and females across the adult lifespan. The data support a model in which age-related differences in fluid intelligence are partially mediated by the responsiveness of frontoparietal regions to novel problem-solving. We first replicate a prior finding of such mediation using an independent sample. We then precisely localize the mediating brain regions, and show that mediation is specifically associated with voxels most activated by cognitive demand, but not with voxels suppressed by cognitive demand. We quantify the robustness of this result to potential unmodeled confounders, and estimate the causal direction of the effects. Finally, exploratory analyses suggest that neural mediation of age-related differences in fluid intelligence is moderated by the variety of regular physical activities, more reliably than by their frequency or duration. An additional moderating role of the variety of nonphysical activities emerged when controlling for head motion. A better understanding of the mechanisms that link healthy aging with lower fluid intelligence may suggest strategies for mitigating such decline.SIGNIFICANCE STATEMENT Global populations are living longer, driving urgency to understand age-related cognitive declines. Fluid intelligence is of prime importance because it reflects performance across many domains, and declines especially steeply during healthy aging. Despite consensus that fluid intelligence is associated with particular frontoparietal brain regions, little research has investigated suggestions that under-responsiveness of these regions mediates age-related decline. We replicate a recent demonstration of such mediation, showing specific association with brain regions most activated by cognitive demand, and robustness to moderate confounding by unmodeled variables. By showing that this mediation model is moderated by the variety of regular physical activities, more reliably than by their frequency or duration, we identify a potential modifiable lifestyle factor that may help promote successful aging.

Is cancer an intelligent species?

Some relevant emerging properties of intelligent systems are "adaptation to a changing environment," "reaction to unexpected situations," "capacity of problem solving," and "ability to communicate." Single cells have remarkable abilities to adapt, make adequate context-dependent decision, take constructive actions, and communicate, thus theoretically meeting all the above-mentioned requirements. From a biological point of view, cancer can be viewed as an invasive species, composed of cells that move from primary to distant sites, being continuously exposed to changes in the environmental conditions. Blood represents the first hostile habitat that a cancer cell encounters once detached from the primary site, so that cancer cells must rapidly carry out multiple adaptation strategies to survive. The aim of this review was to deepen the adaptation mechanisms of cancer cells in the blood microenvironment, particularly referring to four adaptation strategies typical of animal species (phenotypic adaptation, metabolic adaptation, niche adaptation, and collective adaptation), which together define the broad concept of biological intelligence. We provided evidence that the required adaptations (either structural, metabolic, and related to metastatic niche formation) and "social" behavior are useful principles allowing putting into a coherent frame many features of circulating cancer cells. This interpretative frame is described by the comparison with analog behavioral traits typical of various animal models.

From Early Motor Ability to Global Cognitive Development 7 Years after Neonatal Arterial Ischemic Stroke.

The developmental condition of children after neonatal arterial ischemic stroke (NAIS) is characterized by cognitive and motor impairments. We hypothesized that independent walking age would be a predictor of later global cognitive functioning in this population. Sixty-one children with an available independent walking age and full-scale intelligence quotient (IQ) score 7 years after NAIS were included in this study. Full-scale IQ was assessed using the fourth edition of the Wechsler Intelligence Scale for Children (WISC-IV). Independent walking age was negatively correlated with full-scale IQ score at 7 years of age (Pearson correlation coefficient of -0.27; 95% confidence interval from -0.48 to -0.01; p < 0.05). Early motor function is correlated with later global cognitive functioning in children after NAIS. Assessing and promoting early motor ability is essential in this population.

Smart Physical-Based Transdermal Drug Delivery System:Towards Intelligence and Controlled Release.

Transdermal drug delivery systems based on physical principles have provided a stable, efficient, and safe strategy for disease therapy. However, the intelligent device with real-time control and precise drug release is required to enhance treatment efficacy and improve patient compliance. This review summarizes the recent developments, application scenarios, and drug release characteristics of smart transdermal drug delivery systems fabricated with physical principle. Special attention is paid to the progress of intelligent design and concepts in of physical-based transdermal drug delivery technologies for real-time monitoring and precise drug release. In addition, facing with the needs of clinical treatment and personalized medicine, the recent progress and trend of physical enhancement are further highlighted for transdermal drug delivery systems in combination with pharmaceutical dosage forms to achieve better transdermal effects and facilitate the development of smart medical devices. Finally, the next generation and future application scenarios of smart physical-based transdermal drug delivery systems are discussed, a particular focus in vaccine delivery and tumor treatment.

Intuition-and-Tactile Bimodal Sensing Based on Artificial-Intelligence-Motivated All-Fabric Bionic Electronic Skin for Intelligent Material Perception.

Developing electronic skins (e-skins) with extraordinary perception through bionic strategies has far-reaching significance for the intellectualization of robot skins. Here, an artificial intelligence (AI)-motivated all-fabric bionic (AFB) e-skin is proposed, where the overall structure is inspired by the interlocked bionics of the epidermis-dermis interface inside the skin, while the structural design inspiration of the dielectric layer derives from the branch-needle structure of conifers. More importantly, AFB e-skin achieves intuition sensing in proximity mode and tactile sensing in pressure mode based on the fringing and iontronic effects, respectively, and is simulated and verified through COMSOL finite element analysis. The proposed AFB e-skin in pressure mode exhibits maximum sensitivity of 15.06 kPa-1 (<50 kPa), linear sensitivity of 6.06 kPa-1 (50-200 kPa), and fast response/recovery time of 5.6 ms (40 kPa). By integrating AFB e-skin with AI algorithm, and with the support of material inference mechanisms based on dielectric constant and softness/hardness, an intelligent material perception system capable of recognizing nine materials with indistinguishable surfaces within one proximity-pressure cycle is established, demonstrating abilities that surpass human perception.

Long-term intellectual and developmental outcomes after pediatric epilepsy surgery: A systematic review and meta-analysis.

In addition to the primary aim of seizure freedom, a key secondary aim of pediatric epilepsy surgery is to stabilize and, potentially, optimize cognitive development. Although the efficacy of surgical treatment for seizure control has been established, the long-term intellectual and developmental trajectories are yet to be delineated. We conducted a systematic review and meta-analysis of studies reporting pre- and postsurgical intelligence or developmental quotients (IQ/DQ) of children with focal lesional epilepsy aged ≤18 years at epilepsy surgery and assessed at >2 years after surgery. We determined the IQ/DQ change and conducted a random-effects meta-analysis and meta-regression to assess its determinants. We included 15 studies reporting on 341 patients. The weighted mean age at surgery was 7.1 years (range = .3-13.8). The weighted mean postsurgical follow-up duration was 5.6 years (range = 2.7-12.8). The overall estimate of the mean presurgical IQ/DQ was 60 (95% confidence interval [CI] = 47-73), the postsurgical IQ/DQ was 61 (95% CI = 48-73), and the change was +.94 IQ/DQ (95% CI = -1.70 to 3.58, p = .486). Children with presurgical IQ/DQ ≥ 70 showed a tendency for higher gains than those with presurgical IQ/DQ < 70 (p = .059). Higher gains were determined by cessation of antiseizure medication (ASM; p = .041), not just seizure freedom. Our findings indicate, on average, stabilization of intellectual and developmental functioning at long-term follow-up after epilepsy surgery. Once seizure freedom has been achieved, ASM cessation enables the optimization of intellectual and developmental trajectories in affected children.

The interrelatedness of cognitive abilities in very preterm and full-term born children at 5.5 years of age: a psychometric network analysis approach.

BACKGROUND: Very preterm (VP) birth is associated with a considerable risk for cognitive impairment, putting children at a disadvantage in academic and everyday life. Despite lower cognitive ability on the group level, there are large individual differences among VP born children. Contemporary theories define intelligence as a network of reciprocally connected cognitive abilities. Therefore, intelligence was studied as a network of interrelated abilities to provide insight into interindividual differences. We described and compared the network of cognitive abilities, including strength of interrelations between and the relative importance of abilities, of VP and full-term (FT) born children and VP children with below-average and average-high intelligence at 5.5 years. METHODS: A total of 2,253 VP children from the EPIPAGE-2 cohort and 578 FT controls who participated in the 5.5-year-follow-up were eligible for inclusion. The WPPSI-IV was used to measure verbal comprehension, visuospatial abilities, fluid reasoning, working memory, and processing speed. Psychometric network analysis was applied to analyse the data. RESULTS: Cognitive abilities were densely and positively interconnected in all networks, but the strength of connections differed between networks. The cognitive network of VP children was more strongly interconnected than that of FT children. Furthermore, VP children with below average IQ had a more strongly connected network than VP children with average-high IQ. Contrary to our expectations, working memory had the least central role in all networks. CONCLUSIONS: In line with the ability differentiation hypothesis, children with higher levels of cognitive ability had a less interconnected and more specialised cognitive structure. Composite intelligence scores may therefore mask domain-specific deficits, particularly in children at risk for cognitive impairments (e.g., VP born children), even when general intelligence is unimpaired. In children with strongly and densely connected networks, domain-specific deficits may have a larger overall impact, resulting in lower intelligence levels.

Cortical grey matter changes, behavior and cognition in children with sleep disordered breathing.

This paper investigated cortical thickness and volumetric changes in children to better understand the impact of obstructive sleep disordered breathing (SDB) on the neurodevelopment of specific regions of the brain. We also aimed to investigate how these changes were related to the behavioral and cognitive deficits observed in the condition. Neuroimaging, behavioral, and sleep data were obtained from 30 children (15 non-snoring controls, 15 referred for assessment of SDB) aged 7 to 17 years. Gyral-based regions of interest were identified using the Desikan-Killiany atlas. Student's t-tests were used to compare regions of interest between the controls and SDB groups. We found that the cortical thickness was significantly greater in the right caudal anterior cingulate and right cuneus regions and there were volumetric increases in the left caudal middle frontal, bilateral rostral anterior cingulate, left, right, and bilateral caudate brain regions in children with SDB compared with controls. Neither cortical thickness nor volumetric changes were associated with behavioral or cognitive measures. The findings of this study indicate disruptions to neural developmental processes occurring in structural regions of the brain; however, these changes appear unrelated to behavioural or cognitive outcomes.