Higher-order Cognition Research Articles

Autism, early psychosis, and social anxiety disorder: understanding the role of social cognition and its relationship to disability in young adults with disorders characterized by social impairments

Impairments in social cognition are believed contribute to disability, particularly for disorders characterized by difficulties in social interaction. There has been little transdiagnostic investigation of this across social cognition domains in young adults. A total of 199 young adults diagnosed with autism spectrum disorder (ASD; N = 53), early psychosis (EP; N = 51), and social anxiety disorder (SAD; N = 64) were compared against neurotypical controls (NT; N = 31) on a battery of lower and higher-order and self-report social cognition measures. For both ASD and EP, participants showed impaired performance on all lower-order emotion recognition tasks and one higher-order social cognition test. Self-reports of empathy were reduced in all clinical groups and particularly in ASD. For SAD, despite showing no objective social cognition impairment, self-reported empathy was reduced to the same level as EP. Discriminant analysis revealed that self-reported empathy and lower-order emotion recognition tests provide best capacity to differentiate groups. Regressions predicting disability revealed depression as the strongest predictor across all disability measures. Empathy provided additional predictive value for social disability and social interaction anxiety. Overall, results support a similar social-cognitive development profile across ASD and EP. While self-reported empathy differentiated between groups, discrepancy between objective social cognition test performance and self-reported empathy in the SAD group suggests probable threat-related self-monitoring report biases that likely further influence all group outcomes. As depression and empathy were the most important predictors of disability, regardless of diagnostic group, research is required to explore targeted interventions for difficulties in these domains to reduce disability.

Mechanisms underlying prelimbic prefrontal cortex mGlu3/mGlu5-dependent plasticity and reversal learning deficits following acute stress

Stress can precipitate or worsen symptoms of many psychiatric illnesses. Dysregulation of the prefrontal cortex (PFC) glutamate system may underlie these disruptions and restoring PFC glutamate signaling has emerged as a promising avenue for the treatment of stress disorders. Recently, we demonstrated that activation of metabotropic glutamate receptor subtype 3 (mGlu3) induces a postsynaptic form of long-term depression (LTD) that is dependent on the activity of another subtype, mGlu5. Stress exposure disrupted this plasticity, but the underlying signaling mechanisms and involvement in higher-order cognition have not yet been investigated. Acute stress was applied by 20-min restraint and early reversal learning was evaluated in an operant-based food-seeking task. We employed whole-cell patch-clamp recordings of layer 5 prelimbic (PL)-PFC pyramidal cells to examine mGlu3-LTD and several mechanistically distinct mGlu5-dependent functions. Acute stress impaired both mGlu3-LTD and early reversal learning. Interestingly, potentiating mGlu5 signaling with the mGlu5 positive allosteric modulator (PAM) VU0409551 rescued stress-induced deficits in both mGlu3-LTD and reversal learning. Other aspects of PL-PFC mGlu5 function were not disrupted following stress; however, signaling downstream of mGlu5-Homer interactions, phosphoinositide-3-kinase (PI3K), Akt, and glycogen synthase kinase 3β was implicated in these phenomena. These findings demonstrate that acute stress disrupts early reversal learning and PL-PFC-dependent synaptic plasticity and that potentiating mGlu5 function can restore these impairments. These findings provide a framework through which modulating coordinated mGlu3/mGlu5 signaling may confer benefits for the treatment of stress-related psychiatric disorders.

A randomized controlled trial of working memory and processing speed training in schizophrenia.

Although prior research has shown that cognitive training may improve cognition for schizophrenia patients, it is currently unclear which domains of cognition should be targeted in training. One suggestion is to target low- or mid-level cognitive processes. In particular, working memory (WM) and processing speed (PS) have been named as two key areas of impairment in schizophrenia, and two domains of cognition that are linked to higher-order cognition and daily functioning. This study aimed to investigate the near-transfer (transfer of gains to related contexts), far-transfer (transfer of gains to unrelated contexts), and real-world gains associated with WM and PS training in schizophrenia. Eighty-three participants with schizophrenia were recruited and randomly assigned to computerized WM training, PS training, or a no-training control group. Outcome measures included WM, PS, fluid intelligence, executive functioning, social cognition, and daily functioning and symptoms. PS training led to significant gains in untrained PS tasks, as well as gains in far-transfer tasks that required speed of processing. WM training did not lead to gains in untrained WM tasks and showed inconsistent effects on some far-transfer tasks. These results suggest some benefit of domain-specific cognitive training, specifically PS training, in schizophrenia. Far-transfer of gains to other cognitive domains and to real-world functioning may not occur after targeted WM or PS training, though non-specific effects (e.g. through behavioral activation, increased motivation) may lead to improvements in some tasks. Future studies should continue to investigate the mechanisms by which cognitive training may enhance cognition and functioning in schizophrenia.

Neural measures of anticipatory bodily attention in children: Relations with executive function

The ability to selectively direct attention to a certain location or modality is a key neurocognitive skill. One important facet of selective attention is anticipation, a foundational biological construct that bridges basic perceptual processes and higher-order cognition. The current study focuses on the neural correlates of bodily anticipation in 6- to 8-year-old children using a task involving tactile stimulation. Electroencephalographic (EEG) activity over sensorimotor cortex was measured after a visual cue directed children to monitor their right or left hand in anticipation of tactile stimulation. Prior to delivery of the tactile stimulus, a regionally-specific desynchronization of the alpha-range mu rhythm occurred over central electrode sites (C3/C4) contralateral to the cue direction. The magnitude of anticipatory mu rhythm desynchronization was associated with children’s performance on two executive function tasks (Flanker and Card Sort). We suggest that anticipatory mu desynchronization has utility as a specific neural marker of attention focusing in young children, which in turn may be implicated in the development of executive function.

Implicit and explicit processes of higher-order cognition: Study on insight problem solving and person cognition

Implicit and explicit processes of higher-order cognition: Study on insight problem solving and person cognition

Stop in the name of lies: The cost of blocking the truth to deceive.

Most researchers assume that deception involves a conflict between a predominant truth response and a deliberate deceptive response. Such a view is consistent with dual process theories that state that high-order cognition operates through fast-automatic processes that may conflict with slow-deliberate ones. In the present study, we tested whether one must inhibit the truth to deceive in light of inconsistent findings in the literature. One hundred and eighty-nine participants were tested across two Negative Priming paradigms that rest on the logic that the activation of a fast-automatic process will be hampered on a given display if it is inhibited on the previous display. Our findings suggest that truthful responses are predominant in healthy adults, which is why inhibitory control is required to activate a deliberate deceptive mode. We argue that the findings from deception studies could be best accounted for by dual process theories.

Common and distinct patterns of abnormal cortical gyrification in major depression and borderline personality disorder

Abnormal gray matter volume has been consistently reported in patients with major depressive disorder (MDD), but markers of cortical neurodevelopment have been rarely investigated. Also, it is unclear whether there exist common versus distinct spatial patterns of abnormal cortical development across different disorders presenting with negative emotions and deficient affective regulation. In this study, we used structural MRI at 3T to investigate the local gyrification index (LGI), a marker of fetal/infant neurodevelopment, in adult female patients with MDD (n = 22), in adult female patients with borderline personality disorder (BPD) (n = 17), and in controls (n = 22). Reduced cortical folding of the precuneus, the superior parietal gyrus and the parahippocampal gyrus was found in both MDD and BPD patients when compared to controls (p < 0.05, cluster-wise probability [CWP] corrected). MDD patients showed additional hypogyrification of the middle frontal gyrus and the fusiform gyrus when compared to both controls and BPD patients (p < 0.05, CWP corrected). In MDD patients, lower LGI of prefrontal regions was significantly associated with the age of disease onset and with the number of depressive episodes. In BPD patients, lower LGI of orbitofrontal regions was associated with impulsivity. Our findings suggest abnormal early cortical development in MDD, affecting brain regions that have been frequently implied in MDD pathophysiology. However, LGI abnormalities may not be specific for MDD, since MDD and BPD patients also exhibited common patterns of hypogyrification. Hypogyrification of cortical regions associated with higher-order cognition appears to be most pronounced in MDD. Abnormal early cortical neurodevelopment may mediate vulnerability to disorders of emotion.

Challenges in Studying Multidimensional Semantic Representations in the Human Brain.

Concepts are a necessary component of higher-order cognition, and they facilitate the comprehension and production of language. However, because semantic representations are encoded by spatially diverse populations of neurons across frontal, parietal, and temporal lobes, localizing function is

Beyond intelligence: a meta-analytic review of the relationship among metacognition, intelligence, and academic performance

This meta-analytic study estimated the correlations among metacognition, intelligence, and academic performance. Metacognition is higher order cognition and one of the most significant predictors of academic performance. The purpose of this study was to examine the degree to which metacognition predicted academic performance when controlling for intelligence. The analysis of 149 samples from 118 articles revealed that, overall, metacognition weakly correlated with both academic performance and intelligence, and that these relationships were moderated by the type of measurement of metacognition. Furthermore, it was found that metacognition predicted academic performance when controlling for intelligence. Our findings indicate the importance of metacognition in educational practice and provide guidance for assessing metacognition in future research.

Altered Long- and Short-Range Functional Connectivity Density in Healthy Subjects After Sleep Deprivations.

Objective: To investigate the brain functional organization induced by sleep deprivation (SD) using functional connectivity density (FCD) analysis.Methods: Twenty healthy subjects (12 female, 8 male; mean age, 20.6 ± 1.9 years) participated a 24 h sleep deprivation (SD) design. All subjects underwent the MRI scan and attention network test twice, once during rested wakefulness (RW) status, and the other was after 24 h acute SD. FCD was divided into the shortFCD and longFCD. Receiver operating characteristic (ROC) curve was used to evaluate the discriminating ability of those FCD differences in brain areas during the SD status from the RW status, while Pearson correlations was used to evaluate the relationships between those differences and behavioral performances.Results: Subjects at SD status exhibited lower accuracy rate and longer reaction time relative to RW status. Compared with RW, SD had a significant decreased shortFCD in the left cerebellum posterior lobe, right cerebellum anterior lobe, and right orbitofrontal cortex, and increased shortFCD in the left occipital gyrus, bilateral thalamus, right paracentral lobule, bilateral precentral gyrus, and bilateral postcentral gyrus. Compared with RW, SD had a significant increased longFCD in the right precentral gyrus, bilateral postcentral gyrus, and right visuospatial network, and decreased longFCD in the default mode network. The area under the curve values of those specific FCD differences in brain areas were (mean ± std, 0.933 ± 0.035; 0.863~0.977). Further ROC curve analysis demonstrated that the FCD differences in those brain areas alone discriminated the SD status from the RW status with high degree of sensitivities (89.19 ± 6%; 81.3~100%) and specificities (89.15 ± 6.87%; 75~100%). Reaction time showed a negative correlation with the right orbitofrontal cortex (r = −0.48, p = 0.032), and accuracy rate demonstrated a positive correlation with the right default mode network (r = 0.573, p = 0.008).Conclusions: The longFCD and shortFCD analysis might be potential indicator biomarkers to locate the underlying altered intrinsic brain functional organization disturbed by SD. SD sustains the cognitive performance by the decreased high-order cognition related areas and the arousal and sensorimotor related areas.

Isoform-selective phosphoinositide 3-kinase inhibition ameliorates a broad range of fragile X syndrome-associated deficits in a mouse model.

Defects in the phosphoinositide 3-kinase (PI3K) pathway are shared characteristics in several brain disorders, including the inherited intellectual disability and autism spectrum disorder, fragile X syndrome (FXS). PI3K signaling therefore could serve as a therapeutic target for FXS and other brain disorders. However, broad inhibition of such a central signal transduction pathway involved in essential cellular functions may produce deleterious side effects. Pharmacological strategies that selectively correct the overactive components of the PI3K pathway while leaving other parts of the pathway intact may overcome these challenges. Here, we provide the first evidence that disease mechanism-based PI3K isoform-specific inhibition may be a viable treatment option for FXS. FXS is caused by loss of the fragile X mental retardation protein (FMRP), which translationally represses specific messenger RNAs, including the PI3K catalytic isoform p110β. FMRP deficiency increases p110β protein levels and activity in FXS mouse models and in cells from subjects with FXS. Here, we show that a novel, brain-permeable p110β-specific inhibitor, GSK2702926A, ameliorates FXS-associated phenotypes on molecular, cellular, behavioral, and cognitive levels in two different FMRP-deficient mouse models. Rescued phenotypes included increased PI3K downstream signaling, protein synthesis rates, and dendritic spine density, as well as impaired social interaction and higher-order cognition. Several p110β-selective inhibitors, for example, a molecule from the same chemotype as GSK2702926A, are currently being evaluated in clinical trials to treat cancer. Our results suggest that repurposing p110β inhibitors to treat cognitive and behavioral defects may be a promising disease-modifying strategy for FXS and other brain disorders.

A Method for Parasagittal Sectioning for Neuroanatomical Quantification of Brain Structures in the Adult Mouse.

In this article, we present a standardized protocol for fast and robust neuroanatomical phenotyping of the adult mouse brain, which complements a previously published article (doi: 10.1002/cpmo.12) in Current Protocols in Mouse Biology. It is aimed at providing an experimental pipeline within an academic research setting from experimental work to data analysis. Our analysis focuses on one single parasagittal plane, covering the majority of brain regions involved in higher order cognitions such as the cortex, hippocampus, and cerebellum, for a total of 166 parameters of area, length, and cell-level measurements in contrast to 78 parameters in our previously published coronal screen. Benefits of using parasagittal analysis for large-scale neuroanatomic screens are discussed. © 2018 by John Wiley & Sons, Inc.

Impact of Intensive Lifestyle Intervention for Weight Management on Self-Reported Cognitive Function—The Action for Health in Diabetes (Look AHEAD) Randomized Controlled Trial

Background: Intensive lifestyle interventions (ILI) to reduce weight and increase physical activity may preserve higher-order cognition in overweight and obese adults with type 2 diabetes (T2D). Methods: Adults with T2D who enrolled in a randomized clinical trial of a 10-year ILI compared with diabetes support and education (DSE; N=5,084; mean age=58.7 years; mean BMI=35.9 kg/m2; 36.8% racial/ethnic minority) provided self-assessments of difficulty with memory, problem-solving, and decision-making abilities at baseline and over ≥10 years of follow-up. The Health Utilities Index assessed memory and problem-solving; the Beck Depression Inventory-II assessed decision-making. Analyses included the full sample and sub-groups based on baseline weight status and history of cardiovascular disease (CVD). Results: At baseline, 12%, 16%, and 23% of all participants reported some difficulty with problem-solving, decision-making, and memory, respectively. For those without baseline self-identified cognitive difficulties in a specific domain, ILI was associated with lower odds of decision-making difficulties at follow-up compared to DSE (odds ratio [OR]=0.85, [95% CI 0.75,0.97]). Among those who were not obese, ILI was associated with lower odds of problem-solving difficulties at follow-up (OR=0.69 [0.51,0.95]). For participants with self-identified cognitive difficulties at baseline who had a history of CVD, ILI may have worsened difficulties in problem-solving at follow-up visits (OR=2.95 [1.38,6.31]). Conclusions: A long-term ILI targeting weight loss and physical activity may protect self-reported higher-order cognitive abilities in adults with T2D without preexisting memory, problem-solving, or decision-making problems. However, among those with preexisting problems, ILI was not protective. Disclosure G.R. Dutton: None. M. Espeland: Consultant; Self; Boehringer Ingelheim GmbH, Janssen Pharmaceuticals, Inc.. Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Heart, Lung, and Blood Institute. R.H. Neiberg: None. O. Carmichael: None. K.M. Hayden: None. K.C. Johnson: None. R.W. Jeffery: None. L.D. Baker: None. D. Cook: None. D. Kitzman: Advisory Panel; Self; AbbVie Inc.. Research Support; Self; AstraZeneca. S.R. Rapp: None.

Long Non-Coding RNAs in Neuronal Aging.

The expansion of long non-coding RNAs (lncRNAs) in organismal genomes has been associated with the emergence of sophisticated regulatory networks that may have contributed to more complex neuronal processes, such as higher-order cognition. In line with the important roles of lncRNAs in the normal functioning of the human brain, dysregulation of lncRNA expression has been implicated in aging and age-related neurodegenerative disorders. In this paper, we discuss the function and expression of known neuronal-associated lncRNAs, their impact on epigenetic changes, the contribution of transposable elements to lncRNA expression, and the implication of lncRNAs in maintaining the 3D nuclear architecture in neurons. Moreover, we discuss how the complex molecular processes that are orchestrated by lncRNAs in the aged brain may contribute to neuronal pathogenesis by promoting protein aggregation and neurodegeneration. Finally, this review explores the possibility that age-related disturbances of lncRNA expression change the genomic and epigenetic regulatory landscape of neurons, which may affect neuronal processes such as neurogenesis and synaptic plasticity.

The human cortex possesses a reconfigurable dynamic network architecture that is disrupted in psychosis

Higher-order cognition emerges through the flexible interactions of large-scale brain networks, an aspect of temporal coordination that may be impaired in psychosis. Here, we map the dynamic functional architecture of the cerebral cortex in healthy young adults, leveraging this atlas of transient network configurations (states), to identify state- and network-specific disruptions in patients with schizophrenia and psychotic bipolar disorder. We demonstrate that dynamic connectivity profiles are reliable within participants, and can act as a fingerprint, identifying specific individuals within a larger group. Patients with psychotic illness exhibit intermittent disruptions within cortical networks previously associated with the disease, and the individual connectivity profiles within specific brain states predict the presence of active psychotic symptoms. Taken together, these results provide evidence for a reconfigurable dynamic architecture in the general population and suggest that prior reports of network disruptions in psychosis may reflect symptom-relevant transient abnormalities, rather than a time-invariant global deficit.

Alexithymia is associated with a multidomain, multidimensional failure of interoception: Evidence from novel tests.

Interoception, the perception of the body’s internal state, contributes to numerous aspects of higher-order cognition. Several theories suggest a causal role for atypical interoception in specific psychiatric disorders, including a recent claim that atypical interoception represents a transdiagnostic impairment across disorders characterized by reduced perception of one’s own emotion (alexithymia). Such theories are supported predominantly by evidence from only one interoceptive domain (cardiac); however, evidence of domain-specific interoceptive ability highlights the need to assess interoception in noncardiac domains. Using novel interoceptive tasks, we demonstrate that individuals high in alexithymic traits show a reduced propensity to utilize interoceptive cues to gauge respiratory output (Experiment 1), reduced accuracy on tasks of muscular effort (Experiment 2), and taste sensitivity (Experiment 3), unrelated to any co-occurring autism, depression, or anxiety. Results suggest that alexithymia reflects a multidomain, multidimensional failure of interoception, which is consistent with theories suggesting that atypical interoception may underpin both symptom commonalities between psychiatric disorders and heterogeneity within disorders.

Against Cognitivism About Personhood

The present paper unravels ontological and normative conditions of personhood for the purpose of critiquing ‘Cognitivist Views’. Such views have attracted much attention and affirmation by presenting the ontology of personhood in terms of higher-order cognition on the basis of which normative practices are explained and justified. However, these normative conditions are invoked to establish the alleged ontology in the first place. When we want to know what kind of entity has full moral status, it is tempting to establish an ontology that fits our moral intuitions about who should qualify for such unique normative standing. But this approach conflates personhood’s ontology and normativity insofar as it stresses the primacy of the former while implicitly presupposing the latter; it thereby suffers from a ‘Normative Fallacy’ by inferring from ‘ought’ to ‘is’. Following my critique of Cognitivism, I sketch an alternative conception, contending that, whereas the Cognitivist ontology of personhood presupposes the normative, a social ontology is constituted by it. In due consideration of evidence from developmental psychology, the social embeddedness of persons—manifested in the ability of taking a ‘second-person stance’—is identified as a key feature of personhood that precedes higher-order cognition, and is directly linked to basic normative concerns.

The mindedness of maternal touch: An investigation of maternal mind-mindedness and mother-infant touch interactions

Increasing evidence shows that maternal touch may promote emotion regulation in infants, however less is known about how parental higher-order social cognition abilities are translated into tactile, affect-regulatory behaviours towards their infants. During 10 min book-reading, mother-infant sessions when infants were 12 months old (N = 45), we investigated maternal mind-mindedness (MM), the social cognitive ability to understand an infant’s mental state, by coding the contingency of maternal verbal statements towards the infants’ needs and desires. We also rated spontaneous tactile interactions in terms of their emotional contingency. We found that frequent non-attuned mind-related comments were associated with touch behaviours that were not contingent with the infant’s emotions; ultimately discouraging affective tactile responses from the infant. However, comments that were more appropriate to infant’s mental states did not necessarily predict more emotionally-contingent tactile behaviours. These findings suggest that when parental high-order social cognitive abilities are compromised, they are also likely to translate into inappropriate, tactile attempts to regulate infant’s emotions.

The Emotional, Behavioral, and Cognitive Experience of Boundary Turbulence

Key to understanding the process of privacy management is examining how boundary turbulence is individually experienced. Building on the principles of communication privacy management, I considered how the amount of dissemination beyond the dyadic boundary corresponds to the automatic emotional reactions, behavioral responses, and higher-order cognitions reported in response to boundary turbulence. Two hundred sixteen college-aged students described recent privacy breaches and reported their individual emotional, behavioral, and cognitive responses to the betrayal of confidence. Results revealed that the amount of dissemination of private information was positively associated with anger, fear, and sadness. Furthermore, anger incited the use of distributive tactics, and this association was stronger for individuals who ruminated. Congruently, sadness prompted withdrawal behaviors, and this relationship increased as cognitive avoidance increased.

Effects of Nutrition on the Development of Higher-Order Cognition.

The long-chain polyunsaturated fatty acids (LC-PUFAs) docosahexaenoic acid (DHA) and arachidonic acid (ARA) occur in high levels in the brain and play a key role in brain growth and the operation of neurotransmitters. Infants supplemented with DHA show improved language and communication skills, and there is accumulating evidence that the early development of executive functions such as planning, working memory, and attention control are influenced by LC-PUFAs, especially DHA. Several studies have found significantly improved means-end problem solving at 9 and 10 months in infants given DHA-/ARA-supplemented formula, and similar results were shown for infants whose mothers were supplemented with DHA during pregnancy and breastfeeding. Long-term benefits of LC-PUFA supplementation in infancy have been reported in children aged 3-6 years. Follow-up studies of infants given DHA-/ARA-supplemented versus control formula have shown better performance on tests of impulsivity and attention control in the supplemented children, with indications of a dose-response relationship for DHA. LC-PUFAs (especially DHA) in postnatal infant diet influence the development of executive functions and other higher-order cognitive abilities, and have a long-term influence on the development of attention and information processing in later childhood.