Logic, self-awareness and self-improvement: The metacognitive loop and the problem of brittleness

This essay describes a general approach to building perturbation-tolerant autonomous systems, based on the conviction that artificial agents should be able notice when something is amiss, assess the anomaly, and guide a solution into place. We call this basic strategy of self-guided learning the metacognitive loop; it involves the system monitoring, reasoning about, and, when necessary, altering its own decision-making components. In this essay, we (a) argue that equipping agents with a metacognitive loop can help to overcome the brittleness problem, (b) detail the metacognitive loop and its relation to our ongoing work on time-sensitive commonsense reasoning, (c) describe specific, implemented systems whose perturbation tolerance was improved by adding a metacognitive loop, and (d) outline both short-term and long-term research agendas

The roots of self-awareness

In this paper we provide an account of the structural underpinnings of self-awareness. We offer both an abstract, logical account-by way of suggestions for how to build a genuinely self-referring artificial agent-and a biological account, via a discussion of the role of somatoception in supporting and structuring self-awareness more generally. Central to the account is a discussion of the necessary motivational properties of self-representing mental tokens, in light of which we offer a novel definition of self-representation. We also discuss the role of such tokens in organizing self-specifying information, which leads to a naturalized restatement of the guarantee that introspective awareness is immune to error due to mis-identification of the subject

Active Logics: A Unified Formal Approach to Episodic Reasoning

Artificial intelligence research falls roughly into two categories: formal and implementational. This division is not completely firm: there are implementational studies based on (formal or informal) theories (e.g., CYC, SOAR, OSCAR), and there are theories framed with an eye toward implementability (e.g., predicate circumscription). Nevertheless, formal/theoretical work tends to focus on very narrow problems (and even on very special cases of very narrow problems) while trying to get them ``right'' in a very strict sense, while implementational work tends to aim at fairly broad ranges of behavior but often at the expense of any kind of overall conceptually unifying framework that informs understanding. It is sometimes urged that this gap is intrinsic to the topic: intelligence is not a unitary thing for which there will be a unifying theory, but rather a ``society'' of subintelligences whose overall behavior cannot be reduced to useful characterizing and predictive principles. Here we describe a formal architecture that is more closely tied to implementational constraints than is usual for formalisms, and which has been used to solve a number of commonsense problems in a unified manner. In particular, we address the issue of formal, integrated, and longitudinal reasoning: inferentially-modeled behavior that incorporates a fairly wide variety of types of commonsense reasoning within the context of a single extended episode of activity requiring keeping track of ongoing progress, and altering plans and beliefs accordingly. Instead of aiming at optimal solutions to isolated, well-specified and temporally narrow problems, we focus on satisficing solutions to under-specified and temporally-extended problems, much closer to real-world needs. We believe that such a focus is required for AI to arrive at truly intelligent mechanisms with the ability to behave effectively over considerably longer time periods and range of circumstances than is common in AI today. While this will surely lead to less elegant formalisms, it also surely is requisite if AI is to get fully out of the blocks-world and into the real world. (Also cross-referenced as UMIACS-TR-99-65

Efficacy and Tolerability of Adjunctive Intravenous Sodium Nitroprusside Treatment for Outpatients With Schizophrenia: A Randomized Clinical Trial

Importance: Antipsychotic medications for the treatment of schizophrenia have limitations, and new treatments are needed. A prior pilot investigation suggested that adjunctive sodium nitroprusside (SNP) administered intravenously had rapid efficacy in the treatment of patients with schizophrenia. Objective: To determine the efficacy and tolerability of intravenous SNP infused at a rate of 0.5 mug/kg/min for 4 hours in patients with schizophrenia with some degree of treatment resistance. Design, Setting, and Participants: Multicenter, randomized, double-blind acute treatment study using a sequential parallel comparison design conducted in two 2-week phases at 4 academic medical centers beginning May 20, 2015, and ending March 31, 2017. Participants were adults 18 to 65 years of age with a diagnosis of schizophrenia as confirmed by the Structured Clinical Interview for DSM-IV, taking antipsychotic medication for at least 8 weeks, and had at least 1 failed trial of an antipsychotic medication within the past year. A total of 90 participants consented, 60 participants enrolled, and 52 participants were included in the analyses. A modified intent-to-treat analysis was used. Interventions: Participants were randomized in a 1:1:1 ratio to 1 of 3 treatment sequences: SNP and SNP, placebo and SNP, and placebo and placebo. The SNP and SNP group received SNP in phase 1 and SNP in phase 2 for the purpose of blinding, but the data from phase 2 were not included in the results. The placebo and SNP group received placebo in phase 1 and SNP in phase 2. If there was no response to placebo in phase 1, data from phase 2 were included in the analyses. The placebo and placebo group received placebo in both phases; if there was no response to placebo in phase 1, data from phase 2 were included in the analyses. Main Outcomes and Measures: Effectiveness of SNP compared with placebo in improving Positive and Negative Syndrome Scale (PANSS) total, positive, and negative scores across each 2-week phase. Results: Fifty-two participants (12 women and 40 men) were included in the study. In the SNP and SNP group, the mean (SD) age was 47.1 (10.5) years. In the placebo and SNP group, the mean (SD) age was 45.9 (12.3) years. In the placebo and placebo group, the mean (SD) age was 40.4 (11.0) years. There were no significant differences between the SNP and placebo groups at baseline or in change from baseline for PANSS-total (weighted beta = -1.04; z = -0.59; P = .57), PANSS-positive (weighted beta = -0.62; z = -0.93; P = .35), or PANSS-negative (weighted beta = -0.12; z = -0.19; P = .85) scores. No significant differences in safety or tolerability measures were identified. Conclusions and Relevance: Although intravenous SNP is well tolerated, it was not an efficacious adjunctive treatment of positive or negative symptoms of psychosis among outpatients with schizophrenia with prior history of treatment resistance. Trial Registration: ClinicalTrials.gov identifier: NCT02164981

Spoken language processing: piecing together the puzzle

Attempting to understand the fundamental mechanisms underlying spoken language processing, whether it is viewed as behaviour exhibited by human beings or as a faculty simulated by machines, is one of the greatest scientific challenges of our age. Despite tremendous achievements over the past 50 or so years, there is still a long way to go before we reach a comprehensive explanation of human spoken language behaviour and can create a technology with performance approaching or exceeding that of a human being. It is argued that progress is hampered by the fragmentation of the field across many different disciplines, coupled with a failure to create an integrated view of the fundamental mechanisms that underpin one organism's ability to communicate with another. This paper weaves together accounts from a wide variety of different disciplines concerned with the behaviour of living systems - many of them outside the normal realms of spoken language - and compiles them into a new model: PRESENCE (PREdictive SENsorimotor Control and Emulation). It is hoped that the results of this research will provide a sufficient glimpse into the future to give breath to a new generation of research into spoken language processing by mind or machine. (c) 2007 Elsevier B.V. All rights reserved

An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

AbstractBackgroundThe genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder.MethodsWe analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures.ResultsThe SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10–9) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10–9).ConclusionsThis large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression

Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder

Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48x10-7; Bonferroni-corrected significance threshold p < 2.79x10-6). Using summary statistics from the stress-sensitivity term of the GWIS, SNP heritability for stress-sensitivity was estimated at 5.0%. In models fitting polygenic risk scores of both MDD and neuroticism derived from independent GWAS, we show that polygenic risk scores derived from the UK Biobank stress-sensitivity GWIS significantly improved the prediction of MDD in Generation Scotland. This study may improve interpretation of larger genome-wide association studies of MDD and other stress-related illnesses, and the understanding of the etiological mechanisms underpinning stress-sensitivity

Hair Cortisol in Twins : Heritability and Genetic Overlap with Psychological Variables and Stress-System Genes

A. Palotie on työryhmän jäsen.Hair cortisol concentration (HCC) is a promising measure of long-term hypothalamus-pituitary-adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.Peer reviewe

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe