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Objective: To investigate the relation between parental age, and behavioral, cognitive and brain differences in the children. Method: Data with children aged 9–11 of 8709 mothers with parental age 15–45 years were analyzed from the Adolescent Brain Cognitive Development (ABCD) study. A general linear model was used to test the associations of the parental age with brain structure, and behavioral and cognitive problems scores. Results: Behavioral and cognitive problems were greater in the children of the younger mothers, and were associated with lower volumes of cortical regions in the children. There was a linear correlation between the behavioral and cognitive problems scores, and the lower brain volumes (r > 0.6), which was evident when parental age was included as a stratification factor. The regions with lower volume included the anterior cingulate cortex, medial and lateral orbitofrontal cortex and amygdala, parahippocampal gyrus and hippocampus, and temporal lobe (FDR corrected p

Reward processing alterations have been suggested as a candidate mechanism underlying anhedonia and apathy in depression. Neuroimaging studies have documented that neurofunctional alterations in mesocorticolimbic circuits may neurally mediate reward processing deficits in depression. However, common and distinct neurofunctional alterations during motivational and hedonic evaluation of monetary (extrinsic) and natural (intrinsic) rewards in depression have not been systematically examined. Here, we capitalized on a series of pre-registered neuroimaging meta-analyses to (1) establish general reward-related neural alterations in depression, (2) determine common and distinct alterations during anticipation of monetary rewards, receipt of monetary rewards, and receipt of natural rewards, and, (3) characterize the differences on the behavioral, network and molecular level. The coordinate-based meta-analysis included a total of 633 depressed patients and 644 healthy controls and revealed generally decreased subgenual anterior cingulate cortex (ACC) and striatal reactivity towards rewards in depression. Subsequent quantitative comparison analysis indicated that monetary rewards led to decreased hedonic reactivity in the right ventral caudate while natural rewards led to decreased reactivity in the bilateral putamen. These regions exhibited distinguishable profiles on the behavioral, network and receptor level. Further analyses demonstrated that the right thalamus and left putamen showed decreased activation during the anticipation of monetary reward. The present results indicate that distinguishable neurofunctional alterations may neurally mediate reward-processing alterations in depression, particularly with respect to monetary and natural rewards. Given that natural rewards prevail in everyday life, our findings suggest that reward-type specific interventions are warranted and challenge the generalizability of experimental tasks employing monetary incentives to capture reward dysregulations in everyday life.

Funder: Program of Introducing Talents of Discipline to Universities, Plan 111 (No. B18015). National Key R&D Program of China (No. 2018YFC1312900)., Emerging evidence shows that the coronavirus disease 2019 (COVID-19) pandemic is negatively affecting mental health around the globe. Interventions to alleviate the psychological impact of the pandemic are urgently needed. Whether mindfulness practice may protect against the harmful emotional effects of a pandemic crisis remains hitherto unknown. We investigated the influence of mindfulness training on mental health during the COVID-19 outbreak in China. We hypothesized that mindfulness practitioners might manifest less pandemic-related distress, depression, anxiety, and stress than non-practitioners and that more frequent practice would be associated with an improvement in mental health during the pandemic. Therefore, we assessed pandemic-related distress and symptoms of depression, anxiety, and stress, as well as the frequency of meditation practice at the peak of new infections (Feb 4–5; N = 673) and three weeks later (Feb 29–30; N = 521) in mindfulness practitioners via online questionnaires. Self-reported symptoms were also collected from non-practitioners at peak time only (N = 1550). We found lower scores of pandemic-related distress in mindfulness practitioners compared to non-practitioners. In general, older participants showed fewer symptoms of depression and anxiety. In younger practitioners, pandemic-related distress decreased from peak to follow-up. Importantly, increased mindfulness training during the preceding two weeks was associated with lower scores of depression and anxiety at both assessments. Likewise, practice frequency predicted individual improvement in scores of depression, anxiety, and stress at follow-up. Our results indicate that mindfulness meditation might be a viable low-cost intervention to mitigate the psychological impact of the COVID-19 crisis and future pandemics.

The involvement of specific basal ganglia-thalamocortical circuits in response inhibition has been extensively mapped in the last few decades. However, the pivotal brain nodes and directed casual regulation within this inhibitory circuit in humans remains controversial. Here, we capitalize on recent progress in robust and biologically plausible directed causal modelling (DCM-PEB) and a large fMRI response inhibition dataset (n=218) to determine key nodes, their causal regulation and modulation via biological variables (sex) and inhibitory performance in the inhibitory control circuit encompassing the right inferior frontal gyrus (rIFG), caudate nucleus (rCau), globus pallidum (rGP) and thalamus (rThal).The entire neural circuit exhibited high intrinsic connectivity and an increasing rIFG inflow and its causal regulation over the rCau and rThal during response inhibition. In addition, sex and behavioral performance influenced the architecture of the regulatory circuits such that women displayed increased rThal self-inhibition and decreased rThal to GP modulation, while better inhibitory performance was associated with stronger rThal to rIFG communication. Furthermore, control analyses did not reveal a similar key communication in a left lateralized model. Together these findings indicate a pivotal role of the rIFG as input and causal regulator of subcortical response inhibition nodes.

In almost 50 years since Tulving’s seminal episodic/semantic distinction, advances in cognitive neuroscience have fostered a dramatic change in our understanding of declarative memory. Functional neuroimaging evidence reveals considerable overlap in the neural substrates of episodic and semantic memory systems, while studies in clinical populations underscore the blurred boundaries between them. Leveraging new insights on ‘gradients’ of macro-scale and region-specific cortical organisation, we propose that instead of localisations based on categorical cognitive constructs, gradual transitions in neural engagement offer a more parsimonious account of declarative memory. Positioned at the apex of this macro-scale organisation, the default mode network may provide a common neural substrate upon which both semantic and episodic memory representations are anchored.

Down's syndrome is a chromosomal disorder that invariably results in both intellectual disability and Alzheimer's disease neuropathology. However, only a limited number of studies to date have investigated intrinsic brain network organisation in people with Down's syndrome, none of which addressed the links between functional connectivity and Alzheimer's disease. In this cross‐sectional study, we employed 11C‐Pittsburgh Compound‐B (PiB) positron emission tomography in order to group participants with Down's syndrome based on the presence of fibrillar beta‐amyloid neuropathology. We also acquired resting state functional magnetic resonance imaging data to interrogate the connectivity of the default mode network; a large‐scale system with demonstrated links to Alzheimer's disease. The results revealed widespread positive connectivity of the default mode network in people with Down's syndrome (n = 34, ages 30–55, median age = 43.5) and a stark lack of anti‐correlation. However, in contrast to typically developing controls (n = 20, ages 30–55, median age = 43.5), the Down's syndrome group also showed significantly weaker connections in localised frontal and posterior brain regions. Notably, while a comparison of the PiB‐negative Down's syndrome group (n = 19, ages 30–48, median age = 41.0) to controls suggested that alterations in default mode connectivity to frontal brain regions are related to atypical development, a comparison of the PiB‐positive (n = 15, ages 39–55, median age = 48.0) and PiB‐negative Down's syndrome groups indicated that aberrant connectivity in posterior cortices is associated with the presence of Alzheimer's disease neuropathology. Such distinct profiles of altered connectivity not only further our understanding of the brain physiology that underlies these two inherently linked conditions but may also potentially provide a biomarker for future studies of neurodegeneration in people with Down's syndrome.

To investigate the relation between parental age, and behavioral, cognitive and brain differences in the children.Data with children aged 9-11 of 8709 mothers with parental age 15-45 years were analyzed from the Adolescent Brain Cognitive Development (ABCD) study. A general linear model was used to test the associations of the parental age with brain structure, and behavioral and cognitive problems scores.Behavioral and cognitive problems were greater in the children of the younger mothers, and were associated with lower volumes of cortical regions in the children. There was a linear correlation between the behavioral and cognitive problems scores, and the lower brain volumes (r 0.6), which was evident when parental age was included as a stratification factor. The regions with lower volume included the anterior cingulate cortex, medial and lateral orbitofrontal cortex and amygdala, parahippocampal gyrus and hippocampus, and temporal lobe (FDR corrected p 0.01). The lower cortical volumes and areas in the children significantly mediated the association between the parental age and the behavioral and cognitive problems in the children (all p 10Lower parental age is associated with behavioral problems and reduced cognitive performance in the children, and these differences are related to lower volumes and areas of some cortical regions which mediate the effects in the children. The findings are relevant to psychiatric understanding and assessment.

Summary A core goal in cognitive neuroscience is identifying the physical substrates of the patterns of thought that occupy our daily lives. Contemporary views suggest that the landscape of ongoing experience is heterogeneous and can be influenced by features of both the person and the context. This perspective piece considers recent work that explicitly accounts for both the heterogeneity of the experience and context dependence of patterns of ongoing thought. These studies reveal that systems linked to attention and control are important for organizing experience in response to changing environmental demands. These studies also establish a role of the default mode network beyond task-negative or purely episodic content, for example, implicating it in the level of vivid detail in experience in both task contexts and in spontaneous self-generated experiential states. Together, this work demonstrates that the landscape of ongoing thought is reflected in the activity of multiple neural systems, and it is important to distinguish between processes contributing to how the experience unfolds from those linked to how these experiences are regulated., Cognitive Neuroscience; Psychology; Techniques in Neuroscience

Creative thinking is a hallmark of human cognition, which enables us to generate novel and useful ideas. Nevertheless, its emergence within the macro-scale neurocognitive circuitry remains largely unknown. Using resting-state fMRI data from two large population samples (SWU: n = 931; HCP: n = 1001) and a novel “travelling pattern prediction analysis”, here we identified the modularized functional connectivity patterns linked to creative thinking ability, which concurrently explained individual variability across ordinary cognitive abilities such as episodic memory, working memory and relational processing. Further interrogation of this neural pattern with graph theoretical tools revealed both hub-like brain structures and globally-efficient information transfer paths that together may facilitate higher creative thinking ability through the convergence of distinct cognitive operations. Collectively, our results provide reliable evidence for the hypothesized emergence of creative thinking from core cognitive components through neural integration, and thus allude to a significant theoretical advancement in the study of creativity.

Inhibitory control hierarchically regulates cognitive and emotional systems in the service of adaptive goal-directed behavior across changing task demands and environments. While previous studies convergently determined the contribution of prefrontal-striatal systems to general inhibitory control, findings on the specific circuits that mediate the context-specific impact of inhibitory control remained inconclusive. Against this background we employed an evaluated emotional Go/No Go task with fMRI in a large cohort of subjects (N = 250) to segregate brain systems and circuits that mediate domain-general from emotion-specific inhibition control. Particularly during a positive emotional context, behavioral results showed a lower accuracy for No Go trials and a faster response time for Go trials. While the dorsal striatum and lateral frontal regions were involved in inhibitory control irrespective of emotional context, activity in the ventral striatum (VS) and medial orbitofrontal cortex (mOFC) varied as a function of emotional context. On the voxel-wise network level, limbic and striatal systems generally exhibited highest changes in global brain connectivity during inhibitory control, while global brain connectivity of the left mOFC was less suppressed during emotional contexts. Functional connectivity analyses moreover revealed that negative coupling between the VS with inferior frontal gyrus (IFG)/insula and mOFC varied as a function of emotional context. Together these findings indicated separable domain general systems as well emotional context-specific inhibitory brain systems which specifically encompass the VS and its connections with frontal regions.

Humans and other primates can reverse their choice of stimuli in one trial when the rewards delivered by the stimuli change or reverse. Rapidly changing our behavior when the rewards change is important for many types of behavior, including emotional and social behavior. It is shown in a one-trial rule-based Go-NoGo deterministic visual discrimination reversal task to obtain points, that the human right lateral orbitofrontal cortex and adjoining inferior frontal gyrus is activated on reversal trials, when an expected reward is not obtained, and the non-reward allows the human to switch choices based on a rule. This reward reversal goes beyond model-free reinforcement learning. This functionality of the right lateral orbitofrontal cortex shown here in very rapid, one-trial, rule-based changes in human behavior when a reward is not received is related to the emotional and social changes that follow orbitofrontal cortex damage, and to depression in which this non-reward system is oversensitive and over-connected.

Recent accounts of large-scale cortical organisation suggest that the default mode network (DMN) is positioned at the top of a principal gradient, reflecting the separation between heteromodal and unimodal sensory-motor regions in patterns of connectivity and in geodesic distance along the cortical surface (Margulies et al., 2016). This isolation of DMN from external inputs might allow the integration of disparate sources of information that can constrain subsequent cognition. We tested this hypothesis by manipulating the degree to which semantic decisions for ambiguous words (e.g. jam ) were constrained by preceding visual cues depicting relevant spatial contexts (e.g. supermarket or road ) and/or facial emotions (e.g. happy vs. frustrated ). We contrasted (i) the effects of a single preceding cue with a no-cue condition employing scrambled images, and (ii) convergent spatial and emotion cues with single cues. Single cues elicited stronger activation in the multiple demand network relative to no cues, consistent with the requirement to maintain information in working memory. The availability of two convergent cues elicited stronger activation within DMN regions (bilateral angular gyrus, middle temporal gyrus, medial prefrontal cortex, and posterior cingulate), even though behavioural performance was unchanged by cueing – consequently task difficulty is unlikely to account for the observed differences in brain activation. A regions-of-interest analysis along the unimodal-to-heteromodal principal gradient revealed maximal activation for the convergent cue condition at the heteromodal end, corresponding to the DMN. Our findings are consistent with the view that regions of DMN support states of information integration that constrain ongoing cognition and provide a framework for understanding the location of these effects at the heteromodal end of the principal gradient.

Time and research will be of the essence when deducing the long-term consequences of the Covid-19 pandemic for global mental health and emotional well-being. Prior reports from viral outbreaks and emerging evidence from the recent pandemic point towards a potential “tsunami” of stress-related disorders in the aftermath of such traumatic events [1]. In addition to neurological and psychiatric symptoms, including psychosis and neurocognitive dementia-like symptoms observed in Covid-19 patients [2], world-wide surveys at the height of the pandemic suggest increased reports of depression, anxiety and distress across a considerable proportion of medical staff as well as the general public [3]. Grief for the loss of loved ones, helplessness and excessive worry over contracting or spreading the virus to other family members are all significant stressors that may collectively contribute to an imminent rise in symptoms of depression, anxiety and suicidal ideation. Furthermore, social distancing measures for combating the viral outbreak may also have unintended consequences such as social isolation, loneliness, abrupt changes to daily habits, unemployment and financial insecurity, which have all been characterised as risk factors for major depressive and post-traumatic stress disorders with potentially long-lasting effects on brain physiology and function.

Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) are highly prevalent and debilitating disorders. The high overlap on the symptomatic and neurobiological level led to ongoing debates about their diagnostic and neurobiological uniqueness. The present study aims to identify common and disorder-specific neuropathological mechanisms and treatment targets in MDD and GAD. The present study combined categorial and dimensional disorder models with a fully data-driven intrinsic network level analysis (Intrinsic Connectivity Contrast, ICC) to resting state fMRI data acquired in 108 partn = 35 and n = 38 unmedicated patients with first-episode GAD, MDD respectively and n=35 healthy controls). Convergent evidence from categorical and dimensional analyses revealed MDD-specific decreased whole-brain connectivity profiles of the medial prefrontal and dorsolateral prefrontal cortex while GAD was specifically characterized by decreased whole-brain connectivity profiles of the putamen and decreased communication of this region with the amygdala. Together, findings from the present data-driven analysis suggest that intrinsic communication of frontal regions engaged in executive functions and emotion regulation represent depression-specific neurofunctional markers and treatment targets whereas dysregulated intrinsic communication of the striato-amygdala system engaged in reinforcement-based and emotional learning processes represent GAD-specific markers and a promising treatment target.

BackgroundDespite the marked inter-individual variability in the clinical presentation of schizophrenia, it remains unclear the extent to which individual dimensions of psychopathology may be reflected in variability across the collective set of functional brain connections. Here, we address this question using network-based predictive modeling of individual psychopathology along four data-driven symptom dimensions. Follow-up analyses assess the molecular underpinnings of predictive networks by relating them to neurotransmitter-receptor distribution patterns.MethodsWe investigated resting-state fMRI data from 147 schizophrenia patients recruited at seven sites. Individual expression along negative, positive, affective, and cognitive symptom dimensions was predicted using relevance vector machine based on functional connectivity within 17 meta-analytic task-networks following a repeated 10-fold cross-validation and leave-one-site-out analyses. Results were validated in an independent sample. Networks robustly predicting individual symptom dimensions were spatially correlated with density maps of nine receptors/transporters from prior molecular imaging in healthy populations.ResultsTen-fold and leave-one-site-out analyses revealed five predictive network-symptom associations. Connectivity within theory-of-mind, cognitive reappraisal, and mirror neuron networks predicted negative, positive, and affective symptom dimensions, respectively. Cognitive dimension was predicted by theory-of-mind and socio-affective-default networks. Importantly, these predictions generalized to the independent sample. Intriguingly, these two networks were positively associated with D1dopamine receptor and serotonin reuptake transporter densities as well as dopamine-synthesis-capacity.ConclusionsWe revealed a robust association between intrinsic functional connectivity within networks for socio-affective processes and the cognitive dimension of psychopathology. By investigating the molecular architecture, the present work links dopaminergic and serotonergic systems with the functional topography of brain networks underlying cognitive symptoms in schizophrenia.

When unoccupied by an explicit external task, humans engage in a wide range of different types of self-generated thinking. These are often unrelated to the immediate environment and have unique psychological features. Although contemporary perspectives on ongoing thought recognise the heterogeneity of these self-generated states, we lack both a clear understanding of how to classify the specific states, and how they can be mapped empirically. In the current study, we capitalise on advances in machine learning that allow continuous neural data to be divided into a set of distinct temporally re-occurring patterns, or states. We applied this technique to a large set of resting state data in which we also acquired retrospective descriptions of the participants’ experiences during the scan. We found that two of the identified states were predictive of patterns of thinking at rest. One state highlighted a pattern of neural activity commonly seen during demanding tasks, and the time individuals spent in this state was associated with descriptions of experience focused on problem solving in the future. A second state was associated with patterns of activity that are commonly seen under less demanding conditions, and the time spent in it was linked to reports of intrusive thoughts about the past. Finally, we found that these two neural states tended to fall at either end of a neural hierarchy that is thought to reflect the brain’s response to cognitive demands. Together, these results demonstrate that approaches which take advantage of time-varying changes in neural function can play an important role in understanding the repertoire of self-generated states. Moreover, they establish that important features of self-generated ongoing experience are related to variation along a similar vein to those seen when the brain responds to cognitive task demands.

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a developmental condition that often persists into adulthood with extensive negative consequences on quality of life. Despite emerging evidence indicating the genetic basis of ADHD, investigations into the familial expression of latent neurocognitive traits remain limited.MethodsIn a group of adult ADHD probands (n = 20), their unaffected first-degree relatives (n = 20) and typically developing control participants (n = 20), we assessed endophenotypic alterations in the default mode network (DMN) connectivity during resting-state functional magnetic resonance imaging in relation to cognitive performance and clinical symptoms. In an external validation step, we also examined the dimensional nature of this neurocognitive trait in a sample of unrelated healthy young adults (n = 100) from the Human Connectome Project (HCP).ResultsThe results illustrated reduced anti-correlations between the posterior cingulate cortex/precuneus and right middle frontal gyrus that was shared between adult ADHD probands and their first-degree relatives, but not with healthy controls. The observed connectivity alterations were linked to higher ADHD symptoms that was mediated by performance in a sustained attention task. Moreover, this brain-based neurocognitive trait dimensionally explained ADHD symptom variability in the HCP sample.ConclusionsAlterations in the default mode connectivity may represent a dimensional endophenotype of ADHD, hence a significant aspect of the neuropathophysiology of this disorder. As such, brain network organisation can potentially be employed as an important neurocognitive trait to enhance statistical power of genetic studies in ADHD and as a surrogate efficacy endpoint in the development of novel pharmaceuticals.

Ongoing thought patterns constitute important aspects of both healthy and abnormal human cognition. However, the neural mechanisms behind these daily experiences and their contribution to well-being remain a matter of debate. Here, using resting-state fMRI and retrospective thought sampling in a large neurotypical cohort (n = 211), we identified two distinct patterns of thought, broadly describing the participants’ current concerns and future plans, that significantly explained variability in the individual functional connectomes. Consistent with the view that ongoing thoughts are an emergent property of multiple neural systems, network-based analysis highlighted the central importance of both unimodal and transmodal cortices in the generation of these experiences. Importantly, while state-dependent current concerns predicted better psychological health, mediating the effect of functional connectomes, trait-level future plans were related to better social health, yet with no mediatory influence. Collectively, we show that ongoing thoughts can influence the link between brain physiology and well-being., Author Summary Occupying a considerable portion of our waking lives, spontaneous thoughts constitute the foundations of our rich inner mental experiences and well-being. Nevertheless, the neural mechanisms behind this cognitive process and its relation to our mental health remain unresolved. In a large cohort of participants, we show that distinct dimensions of ongoing thoughts emerge from a broad set of whole-brain functional interactions, with certain patterns significantly mediating the link between brain connectivity and psychosocial health. Overall, these results highlight the heterogeneous nature of self-generated thoughts, the content and form of which have a significant influence on the association between our brain physiology and mental well-being.

Patterns of functional interactions across distributed brain regions are suggested to provide a scaffold for the conscious processing of information, with marked topological alterations observed in loss of consciousness. However, establishing a firm link between macro-scale brain network organisation and conscious cognition requires direct investigations into neuropsychologically-relevant architectural modifications across systematic reductions in consciousness. Here we assessed both global and regional disturbances to brain graphs in a group of healthy participants across baseline resting state fMRI as well as two distinct levels of propofol-induced sedation. We found a persistent modular architecture, yet significant reorganisation of brain hubs that formed parts of a wider rich-club collective. Furthermore, the reduction in the strength of rich-club connectivity was significantly associated with the participants' performance in a semantic judgment task, indicating the importance of this higher-order topological feature for conscious cognition. These results highlight a remarkable interplay between global and regional properties of brain functional interactions in supporting conscious cognition that is relevant to our understanding of clinical disorders of consciousness., Scientific Reports, 10 (1), ISSN:2045-2322

Neural activity within the default mode network (DMN) is widely assumed to relate to processing during off-task states, however it remains unclear whether this association emerges from a shared role in self or social content that is common in these conditions. In the current study, we examine the possibility that the role of the DMN in ongoing thought emerges from contributions to specific features of off-task experience such as self-relevant or social content. A group of participants described their experiences while performing a laboratory task over a period of days. In a different session, neural activity was measured while participants performed Self/Other judgements (e.g., Does the word ‘Honest’ apply to you (Self condition) or Barack Obama (Other condition)). Despite the prominence of social and personal content in off-task reports, there was no association with neural activity during off-task trait adjective judgements. Instead, during both Self and Other judgements we found recruitment of caudal posterior cingulate cortex—a core DMN hub—was above baseline for individuals whose laboratory experiences were characterised as detailed. These data provide little support for a role of the DMN in self or other content in the off-task state and instead suggest a role in how on-going thought is represented.

Ongoing thought patterns constitute important aspects of both healthy and abnormal human cognition. However, the neural mechanisms behind these daily experiences and their contribution to well-being remain a matter of debate. Here, using resting state fMRI and retrospective thought sampling in a large neurotypical cohort (n = 211) we identified two distinct patterns of thought, broadly describing the participants current concerns and future plans, that significantly explained variability in the individual functional connectomes. Consistent with the view that ongoing thoughts are an emergent property of multiple neural systems, network-based analysis highlighted the central importance of both unimodal and transmodal cortices in the generation of these experiences. Importantly, while state-dependent current concerns predicted better psychological health, mediating the effect of functional connectomes; trait-level future plans were related to better social health, yet with no mediatory influence. Collectively, we show that ongoing thoughts can influence the link between brain physiology and well-being.

When environments lack compelling goals, humans often let their minds wander to thoughts with greater personal relevance; however, we currently do not understand how this context-dependent prioritisation process operates. Dorsolateral prefrontal cortex (DLPFC) maintains goal representations in a context-dependent manner. Here, we show this region is involved in prioritising off-task thought in an analogous way. In a whole brain analysis we established that neural activity in DLPFC is high both when ‘on-task’ under demanding conditions and ‘off-task’ in a non-demanding task. Furthermore, individuals who increase off-task thought when external demands decrease, show lower correlation between neural signals linked to external tasks and lateral regions of the DMN within DLPFC, as well as less cortical grey matter in regions sensitive to these external task relevant signals. We conclude humans prioritise daydreaming when environmental demands decrease by aligning cognition with their personal goals using DLPFC., The authors show that the dorsolateral prefrontal cortex (DLPFC) is involved in both on-task thought during increased environmental demands, and off-task thought during decreased demand–suggesting a role for the DLPFC in prioritising goals in a context-dependent manner.

The ability to visualise different people and places in imagination is a core element of human cognition. Contemporary neuroimaging research highlights regions of primary visual cortex as important in instantiating images in the mind’s eye. Here we combine task-based functional magnetic resonance imaging with measures of intrinsic brain organisation to show the ventral attention, or salience, network, also plays an important role in visual imagination. In a task-based study we replicated prior observations of regions of medial occipital cortex, including Brodmann Area 17, showing greater neural activity during imagination than when perceiving similar stimuli. In addition, we found regions of the ventral attention network, and in particular right dorsolateral prefrontal cortex (BA 9/46), were activated by the same acts of imagination. In a subsequent resting-state study, we demonstrated medial occipital cortex regions form a functional network with regions of the ventral attention network that were also active during imagination. Furthermore, this pattern was maximised in an overlapping region of right dorsolateral prefrontal cortex for individuals whose self-reported imagery had stronger negative affect. Together these data suggest visual imagination relies on functional interactions between regions of primary visual cortex with the ventral attention system, and in particular, with a region of right dorsolateral prefrontal cortex.

Neural activity within the default mode network (DMN) is widely assumed to relate to processing during off-task states, however it remains unclear whether this association emerges from a shared role in self or social cognition. In the current study, we examine the possibility that the role of the DMN in ongoing thought emerges from contributions to specific features of off-task experience such as self-relevant or social content. A group of participants described their experiences while performing a laboratory task over a period of days. In a different session, neural activity was measured while participants performed self/other judgements. Despite the prominence of social and personal content in off-task reports, there was no association with neural activity during off-task trait adjective judgements. Instead, during both self and other judgements we found recruitment of caudal posterior cingulate cortex - a core DMN hub - was above baseline for individuals whose laboratory experiences were characterised as detailed. These data provide little support for a role of the DMN in self or other content in the off-task state and instead suggest a role in how on-going thought is represented.

ObjectiveTo assess existing literature on the effectiveness of mental health training courses for non-specialist health workers, based on the WHO guidelines (2008).DesignA systematic review was carried out, complying with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist.Data sourcesAfter examination of key studies in the literature, a comprehensive search was performed within the following electronic databases on 31 May 2017: PubMed, PsycINFO, CINAHL (using EBSCOHost interface), Cochrane, Web of Science.Eligibility criteriaSearches were conducted for articles published in English from January 2008 to May 2017, using search terms related to mental health, training, community care and evaluation/outcome, following the Participants, Interventions, Comparators and Outcomes process for evidence-based practice.OutcomesData were collected across the following categories: trainees (number and background), training course (curriculum, teaching method, length), evaluation method (timing of evaluation, collection method and measures assessed) and evaluation outcome (any improvement recorded from baseline). In addition, studies were assessed for their methodological quality using the framework established by Liuet al(2016).Results29 studies with relevant training courses met the inclusion criteria. These were implemented across 16 countries since 2008 (over half between 2014 and 2017), with 10 in three high-income countries. Evaluation methods and outcomes showed high variability across studies, with courses assessing trainees’ attitude, knowledge, clinical practice, skills, confidence, satisfaction and/or patient outcome. All 29 studies found some improvement after training in at least one area, and 10 studies found this improvement to be significant.ConclusionsTraining non-specialist workers in mental healthcare is an effective strategy to increase global provision and capacity, and improves knowledge, attitude, skill and confidence among health workers, as well as clinical practice and patient outcome. Areas for future focus include the development of standardised evaluation methods and outcomes to allow cross-comparison between studies, and optimisation of course structure.PROSPERO registration numberCRD42016033269

Supplemental Digital Content is Available in the Text. Hub topology is altered in fibromyalgia, and disruption of the excitatory tone within the insula influences hub status and is associated with clinical pain intensity., A critical component of brain network architecture is a robust hub structure, wherein hub regions facilitate efficient information integration by occupying highly connected and functionally central roles in the network. Across a wide range of neurological disorders, hub brain regions seem to be disrupted, and the character of this disruption can yield insights into the pathophysiology of these disorders. We applied a brain network–based approach to examine hub topology in fibromyalgia, a chronic pain condition with prominent central nervous system involvement. Resting state functional magnetic resonance imaging data from 40 fibromyalgia patients and 46 healthy volunteers, and a small validation cohort of 11 fibromyalgia patients, were analyzed using graph theoretical techniques to model connections between 264 brain regions. In fibromyalgia, the anterior insulae functioned as hubs and were members of the rich club, a highly interconnected nexus of hubs. In fibromyalgia, rich-club membership varied with the intensity of clinical pain: the posterior insula, primary somatosensory, and motor cortices belonged to the rich club only in patients with the highest pain intensity. Furthermore, the eigenvector centrality (a measure of how connected a region is to other highly connected regions) of the posterior insula positively correlated with clinical pain and mediated the relationship between glutamate + glutamine (assessed by proton magnetic resonance spectroscopy) within this structure and the patient's clinical pain report. Together, these findings reveal altered hub topology in fibromyalgia and demonstrate, for the first time to our knowledge, a neurochemical basis for altered hub strength and its relationship to the perception of pain.

Parkinson’s disease has multiple detrimental effects on motor and cognitive systems in the brain. In contrast to motor deficits, cognitive impairments in Parkinson’s disease are usually not ameliorated, and can even be worsened, by dopaminergic treatments. Recent evidence has shown potential benefits from restoring other neurotransmitter deficits, including noradrenergic and serotonergic transmission. Here, we study global and regional brain network organization using task-free imaging (also known as resting-state), which minimizes performance confounds and the bias towards predetermined networks. Thirty-three patients with idiopathic Parkinson’s disease were studied three times in a double-blinded, placebo-controlled counter-balanced crossover design, following placebo, 40 mg oral atomoxetine (selective noradrenaline reuptake inhibitor) or 30 mg oral citalopram (selective serotonin reuptake inhibitor). Neuropsychological assessments were performed outside the scanner. Seventy-six controls were scanned without medication to provide normative data for comparison to the patient cohort. Graph theoretical analysis of task-free brain connectivity, with a random 500-node parcellation, was used to measure the effect of disease in placebo-treated state (versus unmedicated controls) and pharmacological intervention (drug versus placebo). Relative to controls, patients on placebo had executive impairments (reduced fluency and inhibitory control), which was reflected in dysfunctional network dynamics in terms of reduced clustering coefficient, hub degree and hub centrality. In patients, atomoxetine improved fluency in proportion to plasma concentration (P = 0.006, r2 = 0.24), and improved response inhibition in proportion to increased hub Eigen centrality (P = 0.044, r2 = 0.14). Citalopram did not improve fluency or inhibitory control, but its influence on network integration and efficiency depended on disease severity: clustering (P = 0.01, r2 = 0.22), modularity (P = 0.043, r2 = 0.14) and path length (P = 0.006, r2 = 0.25) increased in patients with milder forms of Parkinson’s disease, but decreased in patients with more advanced disease (Unified Parkinson’s Disease Rating Scale motor subscale part III > 30). This study supports the use of task-free imaging of brain networks in translational pharmacology of neurodegenerative disorders. We propose that hub connectivity contributes to cognitive performance in Parkinson’s disease, and that noradrenergic treatment strategies can partially restore the neural systems supporting executive function., Targeting the deficits in serotonergic and noradrenergic transmission can restore cognitive function in Parkinson’s disease. Borchert et al. use resting-state imaging to show that changes in hub connectivity on atomoxetine correlate with improved response inhibition while the potential therapeutic effect of citalopram depends on severity of disease., Graphical Abstract Graphical Abstract

Understanding the neural processes that support different patterns of ongoing thought is an important goal of contemporary cognitive neuroscience. Early accounts assumed the default mode network (DMN) was especially important for conscious attention to task-irrelevant/personally relevant materials. However, simple task-negative accounts of the DMN are incompatible with more recent evidence that neural patterns within the system can be related to ongoing processing during active task states. To better characterise the contribution of the DMN to ongoing thought, we conducted a cross-sectional analysis of the relationship between the structural organisation of the brain, as indexed by cortical thickness, and patterns of experience, identified using experience sampling in the cognitive laboratory. In a sample of 181 healthy individuals (mean age 20 years, 117 females) we identified an association between cortical thickness in the anterior parahippocampus and patterns of task focused thought, as well as an adjacent posterior region in which cortical thickness was associated with experiences with higher levels of subjective detail. Both regions fell within regions of medial temporal lobe associated with the DMN, yet varied in their functional connectivity: the time series of signals in the 'on-task' region were more correlated with systems important for external task-relevant processing (as determined by meta-analysis) including the dorsal and ventral attention, and fronto-parietal networks. In contrast, connectivity within the region linked to subjective 'detail' was more correlated with the medial core of the DMN (posterior cingulate and the medial pre-frontal cortex) and regions of primary visual cortex. These results provide cross-sectional evidence that confirms a role of the DMN in how detailed experiences are and so provide further evidence that the role of this system in experience is not simply task-irrelevant. Our results also highlight processes within the medial temporal lobe, and their interactions with other regions of cortex, as important in determining multiple aspects of how human cognition unfolds.

The fetal brain shows accelerated growth in the latter half of gestation, and these changes can be captured by 2D and 3D biometry measurements. The aim of this study was to quantify brain growth in normal fetuses using Magnetic Resonance Imaging (MRI) and to produce reference biometry data and a freely available centile calculator (https://www.developingbrain.co.uk/fetalcentiles/). A total of 127 MRI examinations (1.5 T) of fetuses with a normal brain appearance (21–38 gestational weeks) were included in this study. 2D and 3D biometric parameters were measured from slice-to-volume reconstructed images, including 3D measurements of supratentorial brain tissue, lateral ventricles, cortex, cerebellum and extra-cerebral CSF and 2D measurements of brain biparietal diameter and fronto-occipital length, skull biparietal diameter and occipitofrontal diameter, head circumference, transverse cerebellar diameter, extra-cerebral CSF, ventricular atrial diameter, and vermis height, width, and area. Centiles were constructed for each measurement. All participants were invited for developmental follow-up. All 2D and 3D measurements, except for atrial diameter, showed a significant positive correlation with gestational age. There was a sex effect on left and total lateral ventricular volumes and the degree of ventricular asymmetry. The 5th, 50th, and 95th centiles and a centile calculator were produced. Developmental follow-up was available for 73.1% of cases [mean chronological age 27.4 (±10.2) months]. We present normative reference charts for fetal brain MRI biometry at 21–38 gestational weeks. Developing growth trajectories will aid in the better understanding of normal fetal brain growth and subsequently of deviations from typical development in high-risk pregnancies or following premature delivery. Electronic supplementary material The online version of this article (doi:10.1007/s00429-016-1342-6) contains supplementary material, which is available to authorized users.

Conscious experience is dynamic, and its fluidity is particularly marked when attention is not occupied by events in the external world and our minds are free to wander. Our study used measures of neural function, and advanced analyses techniques to examine how unconstrained neural state transitions relate to patterns of ongoing experience. Neural activity was recorded during wakeful rest using functional magnetic resonance imaging and Hidden Markov modelling identified recurrent patterns of brain activity constituting functional dynamic brain states. Individuals making more frequent transitions between states subsequently described experiences highlighting problem solving and lacking unpleasant intrusive features. Frequent switching between states also predicted better health and well-being as assessed by questionnaire. These data provide evidence that the fluidity with which individuals shift through dynamic neural states has an impact on the nature of ongoing thought, and suggest that greater flexibility at rest is an important indicator of a healthy mind.