Publications by authors named "Barbara J Sahakian"

267 Publications

Executive functions and insight in OCD: a comparative study.

BMC Psychiatry 2021 04 29;21(1):216. Epub 2021 Apr 29.

Department of Psychiatry and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Herchel Smith Building for Brain & Mind Sciences, Forvie Site, Robinson Way, Cambridge, CB2 0SZ, UK.

Background: Around 25 to 30% of patients with obsessive-compulsive disorder (OCD) do not respond to treatment. These patients have the longest duration of disease and the worst prognosis. Following years of research on this topic, insight has emerged as a potential explanation for this therapeutic resistance. Therefore, it has become important to characterize OCD patients with poor insight. Few studies have focused on the neuropsychological and cognitive characteristics of these patients.

Methods: To help fill this gap, we divided 57 patients into two groups, one with good insight and the other with poor insight, assessed their neuropsychological functions-through a Rey's figure test, a California verbal learning test, a Toulouse-Piéron test and a Wisconsin Card Sorting Test (WCST)-and compared the results with those of a paired control group.

Results: The statistical analysis, with a significance level of 95%, revealed differences in the executive function tests, and particularly in the WCST (p ≤ 0.001) and trail-making-test (TMT A/B) (p = 0.002).

Conclusions: These differences suggest that the neuropsychological profile of poor-insight patients is different from their good-insight counterparts, emphasize the role played by the executive functions in insight and highlights the need for more accurate neurocognitive research and treatment.
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http://dx.doi.org/10.1186/s12888-021-03227-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082868PMC
April 2021

Executive functions and insight in OCD: a comparative study.

BMC Psychiatry 2021 04 29;21(1):216. Epub 2021 Apr 29.

Department of Psychiatry and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Herchel Smith Building for Brain & Mind Sciences, Forvie Site, Robinson Way, Cambridge, CB2 0SZ, UK.

Background: Around 25 to 30% of patients with obsessive-compulsive disorder (OCD) do not respond to treatment. These patients have the longest duration of disease and the worst prognosis. Following years of research on this topic, insight has emerged as a potential explanation for this therapeutic resistance. Therefore, it has become important to characterize OCD patients with poor insight. Few studies have focused on the neuropsychological and cognitive characteristics of these patients.

Methods: To help fill this gap, we divided 57 patients into two groups, one with good insight and the other with poor insight, assessed their neuropsychological functions-through a Rey's figure test, a California verbal learning test, a Toulouse-Piéron test and a Wisconsin Card Sorting Test (WCST)-and compared the results with those of a paired control group.

Results: The statistical analysis, with a significance level of 95%, revealed differences in the executive function tests, and particularly in the WCST (p ≤ 0.001) and trail-making-test (TMT A/B) (p = 0.002).

Conclusions: These differences suggest that the neuropsychological profile of poor-insight patients is different from their good-insight counterparts, emphasize the role played by the executive functions in insight and highlights the need for more accurate neurocognitive research and treatment.
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http://dx.doi.org/10.1186/s12888-021-03227-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082868PMC
April 2021

"Hot" and "Cold" Cognition in Users of Club Drugs/Novel Psychoactive Substances.

Front Psychiatry 2021 24;12:660575. Epub 2021 Mar 24.

Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.

Novel psychoactive substances (NPS) are popular "club/party" drugs that first attracted attention in the UK in 2009 and remained legal until the 2016 Psychoactive Substances Act criminalized their distribution. Unlike "traditional" illicit drugs, very little is known about the influence of their analogs on neuropsychological functioning. We characterized the cognitive and emotional profile of NPS/polydrug users using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and EMOTICOM test battery in adult male (aged 20-49 years) recreational users without psychiatric comorbidities ( = 27; "psychonauts"), service users attending a UK specialist "Club Drug" Clinic for problematic use ( = 20) and healthy control volunteers without significant drug-taking histories ( = 35). Tasks were selected to distinguish "hot" cognitive processes that are highly influenced by emotion from "cold" cognitive processes that are largely independent of emotional influence. Both user groups reported significantly higher sensation-seeking traits compared with non-users. Recreational NPS users demonstrated more risk-taking behavior compared with controls and treatment-seeking NPS users showed poorer learning, episodic memory and response inhibition compared with the other two groups. These effects persisted, when controlling for age, intelligence, alcohol and cannabis use severity, nicotine dependence, trait anxiety, depression, childhood adversity, impulsivity, and sensation seeking. Overall, recreational NPS users showed elevated "hot" (emotion-laden) cognition in the absence of "cold" (non-emotional) cognitive deficits, whereas "cold" cognitive dysfunction was pronounced in individuals seeking treatment for problematic NPS use. High trait impulsivity and poor self-control may confer additional risk to NPS/polydrug use severity and separate those seeking treatment from those using NPS recreationally.
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http://dx.doi.org/10.3389/fpsyt.2021.660575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024487PMC
March 2021

A decision-neuroscientific intervention to improve cognitive recovery after stroke.

Brain 2021 Mar 20. Epub 2021 Mar 20.

Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany.

Functional recovery after stroke is dose-dependent on the amount of rehabilitative training. However, rehabilitative training is subject to motivational hurdles. Decision neuroscience formalizes drivers and dampers of behaviour and provides strategies for tipping motivational trade-offs and behaviour change. Here, we used one such strategy, upfront voluntary choice restriction ('precommitment'), and tested if it can increase the amount of self-directed rehabilitative training in severely impaired stroke patients. In this randomized controlled study, stroke patients with working-memory deficits (n = 83) were prescribed daily self-directed gamified cognitive training as an add-on to standard therapy during post-acute inpatient neurorehabilitation. Patients allocated to the precommitment intervention could choose to restrict competing options to self-directed training, specifically the possibility to meet visitors. This upfront choice restriction was opted for by all patients in the intervention group and highly effective. Patients in the precommitment group performed the prescribed self-directed gamified cognitive training twice as often as control group patients who were not offered precommitment (on 50% vs. 21% of days, pcorr = .004, d = .87, CI95% = [.31, 1.42]), and, as a consequence, reached a three times higher total training dose (90.21 vs. 33.60 minutes, pcorr = .004, d = .83, CI95%  = [.27, 1.38]). And, add-on self-directed cognitive training was associated with stronger improvements in visuospatial and verbal working-memory performance (pcorr =.002, d = .72, and pcorr = .036, d = .62). Our decision-neuroscientific add-on intervention strongly increased the performed amount of an effective cognitive training in severely impaired stroke patients. These results warrant a full clinical trial to directly link decision neuroscientific interventions to clinical outcome.
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http://dx.doi.org/10.1093/brain/awab128DOI Listing
March 2021

Effect of Tryptophan Depletion on Conditioned Threat Memory Expression: Role of Intolerance of Uncertainty.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 Jan 12. Epub 2021 Jan 12.

Department of Psychology, University of Cambridge, Cambridge, United Kingdom; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.

Background: Responding emotionally to danger is critical for survival. Normal functioning also requires flexible alteration of emotional responses when a threat becomes safe. Aberrant threat and safety learning occur in many psychiatric disorders, including posttraumatic stress disorder, obsessive-compulsive disorder, and schizophrenia, in which emotional responses can persist pathologically. While there is evidence that threat and safety learning can be modulated by the serotonin systems, there have been few studies in humans. We addressed a critical clinically relevant question: How does lowering serotonin affect memory retention of conditioned threat and safety memory?

Methods: Forty-seven healthy participants underwent conditioning to two stimuli predictive of threat on day 1. One stimulus but not the other was subsequently presented in an extinction session. Emotional responding was assessed by the skin conductance response. On day 2, we employed acute dietary tryptophan depletion to lower serotonin temporarily, in a double-blind, placebo-controlled, randomized between-groups design. We then tested for the retention of conditioned threat and extinction memory. We also measured self-reported intolerance of uncertainty, known to modulate threat memory expression.

Results: The expression of emotional memory was attenuated in participants who had undergone tryptophan depletion. Individuals who were more intolerant of uncertainty showed even greater attenuation of emotion following depletion.

Conclusions: These results support the view that serotonin is involved in predicting aversive outcomes and refine our understanding of the role of serotonin in the persistence of emotional responsivity, with implications for individual differences in vulnerability to psychopathology.
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http://dx.doi.org/10.1016/j.bpsc.2020.12.012DOI Listing
January 2021

Serotonin depletion amplifies distinct human social emotions as a function of individual differences in personality.

Transl Psychiatry 2021 Feb 1;11(1):81. Epub 2021 Feb 1.

Department of Psychology, University of Cambridge, Cambridge, UK.

Serotonin is involved in a wide range of mental capacities essential for navigating the social world, including emotion and impulse control. Much recent work on serotonin and social functioning has focused on decision-making. Here we investigated the influence of serotonin on human emotional reactions to social conflict. We used a novel computerised task that required mentally simulating social situations involving unjust harm and found that depleting the serotonin precursor tryptophan-in a double-blind randomised placebo-controlled design-enhanced emotional responses to the scenarios in a large sample of healthy volunteers (n = 73), and interacted with individual differences in trait personality to produce distinctive human emotions. Whereas guilt was preferentially elevated in highly empathic participants, annoyance was potentiated in those high in trait psychopathy, with medium to large effect sizes. Our findings show how individual differences in personality, when combined with fluctuations of serotonin, may produce diverse emotional phenotypes. This has implications for understanding vulnerability to psychopathology, determining who may be more sensitive to serotonin-modulating treatments, and casts new light on the functions of serotonin in emotional processing.
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http://dx.doi.org/10.1038/s41398-020-00880-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847998PMC
February 2021

The Human Brain Is Best Described as Being on a Female/Male Continuum: Evidence from a Neuroimaging Connectivity Study.

Cereb Cortex 2021 Jan 20. Epub 2021 Jan 20.

Institute of Science and Technology for Brain-Inspired Intelligence, Ministry of Education-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence and Research and Research Institute of Intelligent Complex Systems, Fudan University, Shanghai, 200433, China.

Psychological androgyny has long been associated with greater cognitive flexibility, adaptive behavior, and better mental health, but whether a similar concept can be defined using neural features remains unknown. Using the neuroimaging data from 9620 participants, we found that global functional connectivity was stronger in the male brain before middle age but became weaker after that, when compared with the female brain, after systematic testing of potentially confounding effects. We defined a brain gender continuum by estimating the likelihood of an observed functional connectivity matrix to represent a male brain. We found that participants mapped at the center of this continuum had fewer internalizing symptoms compared with those at the 2 extreme ends. These findings suggest a novel hypothesis proposing that there exists a neuroimaging concept of androgyny using the brain gender continuum, which may be associated with better mental health in a similar way to psychological androgyny.
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http://dx.doi.org/10.1093/cercor/bhaa408DOI Listing
January 2021

Can Mobile Technology Help Prevent the Burden of Dementia in Low- and Mid-Income Countries?

Front Public Health 2020 12;8:554938. Epub 2020 Nov 12.

Department of Psychiatry and Behavioural, Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom.

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http://dx.doi.org/10.3389/fpubh.2020.554938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689265PMC
November 2020

Understanding the relationship between cognitive performance and function in daily life after traumatic brain injury.

J Neurol Neurosurg Psychiatry 2020 Dec 2. Epub 2020 Dec 2.

Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

Objective: Cognitive impairment is a key cause of disability after traumatic brain injury (TBI) but relationships with overall functioning in daily life are often modest. The aim is to examine cognition at different levels of function and identify domains associated with disability.

Methods: 1554 patients with mild-to-severe TBI were assessed at 6 months post injury on the Glasgow Outcome Scale-Extended (GOSE), the Short Form-12v2 and a battery of cognitive tests. Outcomes across GOSE categories were compared using analysis of covariance adjusting for age, sex and education.

Results: Overall effect sizes were small to medium, and greatest for tests involving processing speed ( 0.057-0.067) and learning and memory ( 0.048-0.052). Deficits in cognitive performance were particularly evident in patients who were dependent (GOSE 3 or 4) or who were unable to participate in one or more major life activities (GOSE 5). At higher levels of function (GOSE 6-8), cognitive performance was surprisingly similar across categories. There were decreases in performance even in patients reporting complete recovery without significant symptoms. Medium to large effect sizes were present for summary measures of cognition ( 0.111), mental health ( 0.131) and physical health ( 0.252).

Conclusions: This large-scale study provides novel insights into cognitive performance at different levels of disability and highlights the importance of processing speed in function in daily life. At upper levels of outcome, any influence of cognition on overall function is markedly attenuated and differences in mental health are salient.
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http://dx.doi.org/10.1136/jnnp-2020-324492DOI Listing
December 2020

Reward Versus Nonreward Sensitivity of the Medial Versus Lateral Orbitofrontal Cortex Relates to the Severity of Depressive Symptoms.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 Mar 10;6(3):259-269. Epub 2020 Sep 10.

Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, Göttingen, Germany.

Background: The orbitofrontal cortex (OFC) is implicated in depression. The hypothesis investigated was whether the OFC sensitivity to reward and nonreward is related to the severity of depressive symptoms.

Methods: Activations in the monetary incentive delay task were measured in the IMAGEN cohort at ages 14 years (n = 1877) and 19 years (n = 1140) with a longitudinal design. Clinically relevant subgroups were compared at ages 19 (high-severity group: n = 116; low-severity group: n = 206) and 14.

Results: The medial OFC exhibited graded activation increases to reward, and the lateral OFC had graded activation increases to nonreward. In this general population, the medial and lateral OFC activations were associated with concurrent depressive symptoms at both ages 14 and 19 years. In a stratified high-severity depressive symptom group versus control group comparison, the lateral OFC showed greater sensitivity for the magnitudes of activations related to nonreward in the high-severity group at age 19 (p = .027), and the medial OFC showed decreased sensitivity to the reward magnitudes in the high-severity group at both ages 14 (p = .002) and 19 (p = .002). In a longitudinal design, there was greater sensitivity to nonreward of the lateral OFC at age 14 for those who exhibited high depressive symptom severity later at age 19 (p = .003).

Conclusions: Activations in the lateral OFC relate to sensitivity to not winning, were associated with high depressive symptom scores, and at age 14 predicted the depressive symptoms at ages 16 and 19. Activations in the medial OFC were related to sensitivity to winning, and reduced reward sensitivity was associated with concurrent high depressive symptom scores.
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http://dx.doi.org/10.1016/j.bpsc.2020.08.017DOI Listing
March 2021

Obsessive-compulsive disorder-contamination fears, features, and treatment: novel smartphone therapies in light of global mental health and pandemics (COVID-19).

CNS Spectr 2020 Oct 21:1-9. Epub 2020 Oct 21.

Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom.

This review aims to shed light on the symptoms of obsessive-compulsive disorder (OCD) with a focus on contamination fears. In addition, we will briefly review the current therapies for OCD and detail what their limitations are. A key focus will be on discussing how smartphone solutions may provide approaches to novel treatments, especially when considering global mental health and the challenges imposed by rural environments and limited resources; as well as restrictions imposed by world-wide pandemics such as COVID-19. In brief, research that questions this review will seek to address include: (1) What are the symptoms of contamination-related OCD? (2) How effective are current OCD therapies and what are their limitations? (3) How can novel technologies help mitigate challenges imposed by global mental health and pandemics/COVID-19.
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http://dx.doi.org/10.1017/S1092852920001947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691644PMC
October 2020

Association between childhood trauma and risk for obesity: a putative neurocognitive developmental pathway.

BMC Med 2020 10 15;18(1):278. Epub 2020 Oct 15.

Institute of Science and Technology for Brain-Inspired Intelligence, Ministry of Education Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, 200433, People's Republic of China.

Background: Childhood trauma increases the risk for adult obesity through multiple complex pathways, and the neural substrates are yet to be determined.

Methods: Participants from three population-based neuroimaging cohorts, including the IMAGEN cohort, the UK Biobank (UKB), and the Human Connectome Project (HCP), were recruited. Voxel-based morphometry analysis of both childhood trauma and body mass index (BMI) was performed in the longitudinal IMAGEN cohort; validation of the findings was performed in the UKB. White-matter connectivity analysis was conducted to study the structural connectivity between the identified brain region and subdivisions of the hypothalamus in the HCP.

Results: In IMAGEN, a smaller frontopolar cortex (FPC) was associated with both childhood abuse (CA) (β = - .568, 95%CI - .942 to - .194; p = .003) and higher BMI (β = - .086, 95%CI - .128 to - .043; p < .001) in male participants, and these findings were validated in UKB. Across seven data collection sites, a stronger negative CA-FPC association was correlated with a higher positive CA-BMI association (β = - 1.033, 95%CI - 1.762 to - .305; p = .015). Using 7-T diffusion tensor imaging data (n = 156), we found that FPC was the third most connected cortical area with the hypothalamus, especially the lateral hypothalamus. A smaller FPC at age 14 contributed to higher BMI at age 19 in those male participants with a history of CA, and the CA-FPC interaction enabled a model at age 14 to account for some future weight gain during a 5-year follow-up (variance explained 5.8%).

Conclusions: The findings highlight that a malfunctioning, top-down cognitive or behavioral control system, independent of genetic predisposition, putatively contributes to excessive weight gain in a particularly vulnerable population, and may inform treatment approaches.
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http://dx.doi.org/10.1186/s12916-020-01743-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559717PMC
October 2020

Psychological mechanisms and functions of 5-HT and SSRIs in potential therapeutic change: Lessons from the serotonergic modulation of action selection, learning, affect, and social cognition.

Neurosci Biobehav Rev 2020 12 12;119:138-167. Epub 2020 Sep 12.

Department of Psychology, University of Cambridge, Cambridge, UK; Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.

Uncertainty regarding which psychological mechanisms are fundamental in mediating SSRI treatment outcomes and wide-ranging variability in their efficacy has raised more questions than it has solved. Since subjective mood states are an abstract scientific construct, only available through self-report in humans, and likely involving input from multiple top-down and bottom-up signals, it has been difficult to model at what level SSRIs interact with this process. Converging translational evidence indicates a role for serotonin in modulating context-dependent parameters of action selection, affect, and social cognition; and concurrently supporting learning mechanisms, which promote adaptability and behavioural flexibility. We examine the theoretical basis, ecological validity, and interaction of these constructs and how they may or may not exert a clinical benefit. Specifically, we bridge crucial gaps between disparate lines of research, particularly findings from animal models and human clinical trials, which often seem to present irreconcilable differences. In determining how SSRIs exert their effects, our approach examines the endogenous functions of 5-HT neurons, how 5-HT manipulations affect behaviour in different contexts, and how their therapeutic effects may be exerted in humans - which may illuminate issues of translational models, hierarchical mechanisms, idiographic variables, and social cognition.
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http://dx.doi.org/10.1016/j.neubiorev.2020.09.001DOI Listing
December 2020

Covid-19 and promising solutions to combat symptoms of stress, anxiety and depression.

Neuropsychopharmacology 2021 01;46(1):217-218

Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, PR China.

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http://dx.doi.org/10.1038/s41386-020-00791-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425273PMC
January 2021

Heritability of specific cognitive functions and associations with schizophrenia spectrum disorders using CANTAB: a nation-wide twin study.

Psychol Med 2020 Aug 11:1-14. Epub 2020 Aug 11.

Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS) and Center for Neuropsychiatric Schizophrenia Research, Mental Health Center Glostrup, Glostrup, Denmark.

Background: Many cognitive functions are under strong genetic control and twin studies have demonstrated genetic overlap between some aspects of cognition and schizophrenia. How the genetic relationship between specific cognitive functions and schizophrenia is influenced by IQ is currently unknown.

Methods: We applied selected tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) to examine the heritability of specific cognitive functions and associations with schizophrenia liability. Verbal and performance IQ were estimated using The Wechsler Adult Intelligence Scale-III and the Danish Adult Reading Test. In total, 214 twins including monozygotic (MZ = 32) and dizygotic (DZ = 22) pairs concordant or discordant for a schizophrenia spectrum disorder, and healthy control pairs (MZ = 29, DZ = 20) were recruited through the Danish national registers. Additionally, eight twins from affected pairs participated without their sibling.

Results: Significant heritability was observed for planning/spatial span (h2 = 25%), self-ordered spatial working memory (h2 = 64%), sustained attention (h2 = 56%), and movement time (h2 = 47%), whereas only unique environmental factors contributed to set-shifting, reflection impulsivity, and thinking time. Schizophrenia liability was associated with planning/spatial span (rph = -0.34), self-ordered spatial working memory (rph = -0.24), sustained attention (rph = -0.23), and set-shifting (rph = -0.21). The association with planning/spatial span was not driven by either performance or verbal IQ. The remaining associations were shared with performance, but not verbal IQ.

Conclusions: This study provides further evidence that some cognitive functions are heritable and associated with schizophrenia, suggesting a partially shared genetic etiology. These functions may constitute endophenotypes for the disorder and provide a basis to explore genes common to cognition and schizophrenia.
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http://dx.doi.org/10.1017/S0033291720002858DOI Listing
August 2020

The muscarinic M receptor modulates associative learning and memory in psychotic disorders.

Neuroimage Clin 2020 26;27:102278. Epub 2020 May 26.

Department of Psychiatry and Psychology, University of Maastricht, Maastricht, The Netherlands.

Background: Psychotic disorders are characterized by prominent deficits in associative learning and memory for which there are currently no effective treatments. Functional magnetic resonance imaging (fMRI) studies in psychotic disorders have identified deficits in fronto-temporal activation during associative learning and memory. The underlying pathology of these findings remains unclear. Postmortem data have suggested these deficits may be related to loss of muscarinic M receptor mediated signaling. This is supported by an in-vivo study showing improvements in these symptoms after treatment with the experimental M receptor agonist xanomeline. The current study tests whether reported deficits in fronto-temporal activation could be mediated by loss of M receptor signaling in psychotic disorders.

Methods: Twenty-six medication-free subjects diagnosed with a psychotic disorder and 29 age-, gender-, and IQ-matched healthy controls underwent two functional magnetic resonance imaging (fMRI) sessions, one under placebo and one under selective M antagonist biperiden, while performing the paired associated learning task. M binding potentials (BP) were measured in the dorsolateral prefrontal cortex (DLPFC) and hippocampus using I-IDEX single photon emission computed tomography.

Results: In the subjects with psychotic disorders DLPFC hypoactivation was only found in the memory phase of the task. In both learning and memory phases of the task, M antagonism by biperiden elicited significantly greater hyperactivation of the parahippocampal gyrus and superior temporal gyrus in subjects with a psychotic disorders compared to controls. Greater hyperactivation of these areas after biperiden was associated with greater hippocampal M receptor binding during learning, with no association found with M receptor binding in the DLPFC. M receptor binding in the DLPFC was related to greater functional sensitivity to biperiden of the cingulate gyrus during the memory phase.

Conclusion: The current study is the first to show differences in M receptor mediated functional sensitivity between subjects with a psychotic disorder and controls during a paired associate learning and memory task. Results point to subjects with psychotic disorders having a loss of M receptor reserve in temporal-limbic areas.
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http://dx.doi.org/10.1016/j.nicl.2020.102278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305431PMC
March 2021

Mild traumatic brain injury recovery: a growth curve modelling analysis over 2 years.

J Neurol 2020 Nov 13;267(11):3223-3234. Epub 2020 Jun 13.

Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK.

Background: An improved understanding of the trajectory of recovery after mild traumatic brain injury is important to be able to understand individual patient outcomes, for longitudinal patient care and to aid the design of clinical trials.

Objective: To explore changes in health, well-being and cognition over the 2 years following mTBI using latent growth curve (LGC) modelling.

Methods: Sixty-one adults with mTBI presenting to a UK Major Trauma Centre completed comprehensive longitudinal assessment at up to five time points after injury: 2 weeks, 3 months, 6 months, 1 year and 2 years.

Results: Persisting problems were seen with neurological symptoms, cognitive issues and poor quality of life measures including 28% reporting incomplete recovery on the Glasgow Outcome Score Extended at 2 years. Harmful drinking, depression, psychological distress, disability, episodic memory and working memory did not improve significantly over the 2 years following injury. For other measures, including the Rivermead Post-Concussion Symptoms and Quality of Life after Brain Injury (QOLIBRI), LGC analysis revealed significant improvement over time with recovery tending to plateau at 3-6 months.

Interpretation: Significant impairment may persist as late as 2 years after mTBI despite some recovery over time. Longitudinal analyses which make use of all available data indicate that recovery from mTBI occurs over a longer timescale than is commonly believed. These findings point to the need for long-term management of mTBI targeting individuals with persisting impairment.
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http://dx.doi.org/10.1007/s00415-020-09979-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578150PMC
November 2020

Disturbances across whole brain networks during reward anticipation in an abstinent addiction population.

Neuroimage Clin 2020 26;27:102297. Epub 2020 May 26.

Neuropsychopharmacology Unit, Centre for Psychiatry, Imperial College London, United Kingdom.

The prevalent spatial distribution of abnormalities reported in cognitive fMRI studies in addiction suggests there are extensive disruptions across whole brain networks. Studies using resting state have reported disruptions in network connectivity in addiction, but these studies have not revealed characteristics of network functioning during critical psychological processes that are disrupted in addiction populations. Analytic methods that can capture key features of whole brain networks during psychological processes may be more sensitive in revealing additional and widespread neural disturbances in addiction, that are the provisions for relapse risk, and targets for medication development. The current study compared a substance addiction (ADD; n = 83) group in extended abstinence with a control (CON; n = 68) group on functional MRI (voxel-wise activation) and global network (connectivity) measures related to reward anticipation on a monetary incentive delay task. In the absence of group differences on MID performance, the ADD group showed reduced activation predominantly across temporal and visual regions, but not across the striatum. The ADD group also showed disruptions in global network connectivity (lower clustering coefficient and higher characteristic path length), and significantly less connectivity across a sub-network comprising frontal, temporal, limbic and striatal nodes. These results show that an addiction group in extended abstinence exhibit localised disruptions in brain activation, but more extensive disturbances in functional connectivity across whole brain networks. We propose that measures of global network functioning may be more sensitive in highlighting latent and more widespread neural disruptions during critical psychological processes in addiction and other psychiatric disorders.
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http://dx.doi.org/10.1016/j.nicl.2020.102297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270610PMC
March 2021

Influence of Concomitant Extracranial Injury on Functional and Cognitive Recovery From Mild Versus Moderateto Severe Traumatic Brain Injury.

J Head Trauma Rehabil 2020 Nov/Dec;35(6):E513-E523

University Division of Anaesthesia, Department of Medicine (Drs Carroll, Menon, and Newcombe and Mss Manktelow, Outtrim, Chatfield, and Forsyth), Academic Department of Neurosurgery, Department of Clinical Neurosciences (Dr Hutchinson), Wolfson Brain Imaging Centre, Department of Clinical Neurosciences (Drs Sahakian, Menon, and Newcombe), Department of Psychiatry (Dr Sahakian), and Behavioural & Clinical Neuroscience Institute (Dr Sahakian), University of Cambridge, Cambridge, United Kingdom; Turku Brain Injury Center, University of Turku, Turku, Finland (Drs Tenovuo and Posti); Turku University Hospital, Turku, Finland (Drs Tenovuo and Posti); Department of Neurosurgery, Turku University Hospital, Turku, Finland (Dr Posti); and Division of Psychology, University of Stirling, Stirling, United Kingdom (Dr Wilson).

Objective: To determine the effect of extracranial injury (ECI) on 6-month outcome in patients with mild traumatic brain injury (TBI) versus moderate-to-severe TBI.

Participants/setting: Patients with TBI (n = 135) or isolated orthopedic injury (n = 25) admitted to a UK major trauma center and healthy volunteers (n = 99).

Design: Case-control observational study.

Main Measures: Primary outcomes: (a) Glasgow Outcome Scale Extended (GOSE), (b) depression, (c) quality of life (QOL), and (d) cognitive impairment including verbal fluency, episodic memory, short-term recognition memory, working memory, sustained attention, and attentional flexibility.

Results: Outcome was influenced by both TBI severity and concomitant ECI. The influence of ECI was restricted to mild TBI; GOSE, QOL, and depression outcomes were significantly poorer following moderate-to-severe TBI than after isolated mild TBI (but not relative to mild TBI plus ECI). Cognitive impairment was driven solely by TBI severity. General health, bodily pain, semantic verbal fluency, spatial recognition memory, working memory span, and attentional flexibility were unaffected by TBI severity and additional ECI.

Conclusion: The presence of concomitant ECI ought to be considered alongside brain injury severity when characterizing the functional and neurocognitive effects of TBI, with each presenting challenges to recovery.
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http://dx.doi.org/10.1097/HTR.0000000000000575DOI Listing
May 2020

Biological and clinical characteristics of gene carriers far from predicted onset in the Huntington's disease Young Adult Study (HD-YAS): a cross-sectional analysis.

Lancet Neurol 2020 06 26;19(6):502-512. Epub 2020 May 26.

Huntington's Disease Centre, Department of Neurodegenerative disease, UCL Queen Square Institute of Neurology, University College London, London, UK; Dementia Research Institute at University College London, London, UK. Electronic address:

Background: Disease-modifying treatments are in development for Huntington's disease; crucial to their success is to identify a timepoint in a patient's life when there is a measurable biomarker of early neurodegeneration while clinical function is still intact. We aimed to identify this timepoint in a novel cohort of young adult premanifest Huntington's disease gene carriers (preHD) far from predicted clinical symptom onset.

Methods: We did the Huntington's disease Young Adult Study (HD-YAS) in the UK. We recruited young adults with preHD and controls matched for age, education, and sex to ensure each group had at least 60 participants with imaging data, accounting for scan fails. Controls either had a family history of Huntington's disease but a negative genetic test, or no known family history of Huntington's disease. All participants underwent detailed neuropsychiatric and cognitive assessments, including tests from the Cambridge Neuropsychological Test Automated Battery and a battery assessing emotion, motivation, impulsivity and social cognition (EMOTICOM). Imaging (done for all participants without contraindications) included volumetric MRI, diffusion imaging, and multiparametric mapping. Biofluid markers of neuronal health were examined using blood and CSF collection. We did a cross-sectional analysis using general least-squares linear models to assess group differences and associations with age and CAG length, relating to predicted years to clinical onset. Results were corrected for multiple comparisons using the false discovery rate (FDR), with FDR <0·05 deemed a significant result.

Findings: Data were obtained between Aug 2, 2017, and April 25, 2019. We recruited 64 young adults with preHD and 67 controls. Mean ages of participants were 29·0 years (SD 5·6) and 29·1 years (5·7) in the preHD and control groups, respectively. We noted no significant evidence of cognitive or psychiatric impairment in preHD participants 23·6 years (SD 5·8) from predicted onset (FDR 0·22-0·87 for cognitive measures, 0·31-0·91 for neuropsychiatric measures). The preHD cohort had slightly smaller putamen volumes (FDR=0·03), but this did not appear to be closely related to predicted years to onset (FDR=0·54). There were no group differences in other brain imaging measures (FDR >0·16). CSF neurofilament light protein (NfL), plasma NfL, and CSF YKL-40 were elevated in this far-from-onset preHD cohort compared with controls (FDR<0·0001, =0·01, and =0·03, respectively). CSF NfL elevations were more likely in individuals closer to expected clinical onset (FDR <0·0001).

Interpretation: We report normal brain function yet a rise in sensitive measures of neurodegeneration in a preHD cohort approximately 24 years from predicted clinical onset. CSF NfL appears to be a more sensitive measure than plasma NfL to monitor disease progression. This preHD cohort is one of the earliest yet studied, and our findings could be used to inform decisions about when to initiate a potential future intervention to delay or prevent further neurodegeneration while function is intact.

Funding: Wellcome Trust, CHDI Foundation.
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http://dx.doi.org/10.1016/S1474-4422(20)30143-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254065PMC
June 2020

Auditory versus visual neuroscience-informed cognitive training in schizophrenia: Effects on cognition, symptoms and quality of life.

Schizophr Res 2020 08 21;222:319-326. Epub 2020 May 21.

Instituto de Ciencias Biomedicas, Universidade Federal do Rio de Janeiro, Brazil; Instituto de Psiquiatria, Universidade Federal do Rio de Janeiro, Brazil. Electronic address:

Background: Cognitive impairments are related to deficits in primary auditory and visual sensory processes in schizophrenia. These impairments can be remediated by neuroscience-informed computerized cognitive trainings that target auditory and visual processes. However, it is not clear which modality results in greater improvements in cognition, symptoms and quality of life. We aimed to investigate the impact of training auditory versus visual cognitive processes in global cognition in patients with schizophrenia.

Methods: Seventy-nine schizophrenia participants were randomly assigned to either 40 h of auditory or visual computerized training. Auditory and visual exercises were chosen to be dynamically equivalent and difficulties increased progressively during the training. We evaluated cognition, symptoms and quality of life before, after 20 h, and after 40 h of training. ClinicalTrials.gov (1R03TW009002-01).

Results: Participants who received the visual training showed significant improvements in global cognition compared to the auditory training group. The visual training significantly improved attention and reasoning and problem-solving, while the auditory training improved reasoning and problem-solving only. Schizophrenia symptoms improved after training in both groups, whereas quality of life remained unchanged. Interestingly, there was a significant and positive correlation between improvements in attention and symptoms in the visual training group.

Conclusions: We conclude that the visual training and the auditory training are differentially efficient at remediating cognitive deficits and symptoms of clinically stable schizophrenia patients. Ongoing follow-up of participants will evaluate the durability of training effects on cognition and symptoms, as well as the potential impact on quality of life over time.
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http://dx.doi.org/10.1016/j.schres.2020.05.017DOI Listing
August 2020

What Is the Link Between Attention-Deficit/Hyperactivity Disorder and Sleep Disturbance? A Multimodal Examination of Longitudinal Relationships and Brain Structure Using Large-Scale Population-Based Cohorts.

Biol Psychiatry 2020 09 31;88(6):459-469. Epub 2020 Mar 31.

Institute of Science and Technology for Brain-Inspired Intelligence, MOE Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China; Behavioural and Clinical Neuroscience Institute, Department of Psychology, University of Cambridge, Cambridge, United Kingdom; Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.

Background: Attention-deficit/hyperactivity disorder (ADHD) comorbid with sleep disturbances can produce profound disruption in daily life and negatively impact quality of life of both the child and the family. However, the temporal relationship between ADHD and sleep impairment is unclear, as are underlying common brain mechanisms.

Methods: This study used data from the Quebec Longitudinal Study of Child Development (n = 1601, 52% female) and the Adolescent Brain Cognitive Development Study (n = 3515, 48% female). Longitudinal relationships between symptoms were examined using cross-lagged panel models. Gray matter volume neural correlates were identified using linear regression. The transcriptomic signature of the identified brain-ADHD-sleep relationship was characterized by gene enrichment analysis. Confounding factors, such as stimulant drugs for ADHD and socioeconomic status, were controlled for.

Results: ADHD symptoms contributed to sleep disturbances at one or more subsequent time points in both cohorts. Lower gray matter volumes in the middle frontal gyrus and inferior frontal gyrus, amygdala, striatum, and insula were associated with both ADHD symptoms and sleep disturbances. ADHD symptoms significantly mediated the link between these structural brain abnormalities and sleep dysregulation, and genes were differentially expressed in the implicated brain regions, including those involved in neurotransmission and circadian entrainment.

Conclusions: This study indicates that ADHD symptoms and sleep disturbances have common neural correlates, including structural changes of the ventral attention system and frontostriatal circuitry. Leveraging data from large datasets, these results offer new mechanistic insights into this clinically important relationship between ADHD and sleep impairment, with potential implications for neurobiological models and future therapeutic directions.
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http://dx.doi.org/10.1016/j.biopsych.2020.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445427PMC
September 2020

Neural Correlates of the Dual-Pathway Model for ADHD in Adolescents.

Am J Psychiatry 2020 09 7;177(9):844-854. Epub 2020 May 7.

Institute of Science and Technology for Brain-Inspired Intelligence, Ministry of Education-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China (Shen, Luo, Jia, Feng, Sahakian); State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science and Human Phenome Institute, Fudan University, Shanghai, China (Luo); Departments of Psychology and Psychiatry and the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, U.K. (Sahakian); Medical Research Council-Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London (Desrivières, Quinlan, Schumann); School of Mathematical Sciences, Fudan University, Shanghai, China (Zhao); Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (Banaschewski, Millenet, Nees); Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin (Bokde); University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Büchel); Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (Flor, Nees); Department of Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany (Flor); Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig Holstein, Kiel University, Kiel, Germany (Nees); NeuroSpin, Commissariat à l'Énergie Atomique, Université Paris-Saclay, Gif-sur-Yvette, France (Frouin, Orfanos); Departments of Psychiatry and Psychology, University of Vermont, Burlington (Garavan); Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, U.K. (Gowland); Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin (Heinz, Walter); Physikalisch-Technische Bundesanstalt Braunschweig and Berlin (Ittermann); Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 1000, Neuroimaging and Psychiatry, University Paris Sud-Paris Saclay, University Paris Descartes, Paris (Martinot, Artiges, Paillère-Martinot); Service Hospitalier Frédéric Joliot, Orsay, France (Martinot, Artiges); Maison de Solenn, Paris (Martinot); Groupe Hospitalier Nord Essonne, Department of Psychiatry, Orsay, France (Artiges); Assistance Publique-Hôpitaux de Paris, Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, Paris (Paillère-Martinot); Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto (Paus); Departments of Psychology and Psychiatry, University of Toronto, Toronto (Paus); Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany (Poustka); Clinic for Child and Adolescent Psychiatry, Medical University of Vienna, Vienna (Poustka); Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany (Fröhner, Smolka); School of Psychology and Global Brain Health Institute, Trinity College Dublin (Whelan); Developmental and Behavioral Pediatric Department and Child Primary Care Department, Ministry of Education-Shanghai Key Lab for Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China (Li, Sahakian); Department of Computer Science, University of Warwick, Coventry, U.K. (Feng); and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China (Feng).

Objective: The dual-pathway model has been proposed to explain the heterogeneity in symptoms of attention deficit hyperactivity disorder (ADHD) by two independent psychological pathways based on distinct brain circuits. The authors sought to test whether the hypothesized cognitive and motivational pathways have separable neural correlates.

Methods: In a longitudinal community-based cohort of 1,963 adolescents, the neuroanatomical correlates of ADHD were identified by a voxel-wise association analysis and then validated using an independent clinical sample (99 never-medicated patients with ADHD, 56 medicated patients with ADHD, and 267 healthy control subjects). The cognitive and motivational pathways were assessed by neuropsychological tests of working memory, intrasubject variability, stop-signal reaction time, and delay discounting. The associations were tested between the identified neuroanatomical correlates and both ADHD symptoms 2 years later and the polygenic risk score for ADHD.

Results: Gray matter volumes of both a prefrontal cluster and a posterior occipital cluster were negatively associated with inattention. Compared with healthy control subjects, never-medicated patients, but not medicated patients, had significantly lower gray matter volumes in these two clusters. Working memory and intrasubject variability were associated with the posterior occipital cluster, and delay discounting was independently associated with both clusters. The baseline gray matter volume of the posterior occipital cluster predicted the inattention symptoms in a 2-year follow-up and was associated with the genetic risk for ADHD.

Conclusions: The dual-pathway model has both shared and separable neuroanatomical correlates, and the shared correlate in the occipital cortex has the potential to serve as an imaging trait marker of ADHD, especially the inattention symptom domain.
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http://dx.doi.org/10.1176/appi.ajp.2020.19020183DOI Listing
September 2020

Neuroethical issues in cognitive enhancement: Modafinil as the example of a workplace drug?

Brain Neurosci Adv 2019 Jan-Dec;3:2398212818816018. Epub 2019 Feb 15.

Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.

The use of cognitive-enhancing drugs by healthy individuals has been a feature for much of recorded history. Cocaine and amphetamine are modern cases of drugs initially enthusiastically acclaimed for enhancing cognition and mood. Today, an increasing number of healthy people are reported to use cognitive-enhancing drugs, as well as other interventions, such as non-invasive brain stimulation, to maintain or improve work performance. Cognitive-enhancing drugs, such as methylphenidate and modafinil, which were developed as treatments, are increasingly being used by healthy people. Modafinil not only affects 'cold' cognition, but also improves 'hot' cognition, such as emotion recognition and task-related motivation. The lifestyle use of 'smart drugs' raises both safety concerns as well as ethical issues, including coercion and increasing disparity in society. As a society, we need to consider which forms of cognitive enhancement (e.g. pharmacological, exercise, lifelong learning) are acceptable and for which groups under what conditions and by what methods we would wish to improve and flourish.
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http://dx.doi.org/10.1177/2398212818816018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058249PMC
February 2019

Correction: Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios.

Transl Psychiatry 2020 Feb 12;10(1):63. Epub 2020 Feb 12.

Developmental and Behavioral Pediatric Department & Child Primary Care Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and MOE- Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

An important detail was omitted in the Method of the original Article, I.E, The CARS and other evaluations were conducted 'blind' to condition (Bumetanide or no treatment) by experienced clinicians. This has now been updated in the HTML and PDF versions of this Article.
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http://dx.doi.org/10.1038/s41398-020-0747-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026073PMC
February 2020

Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios.

Transl Psychiatry 2020 01 27;10(1). Epub 2020 Jan 27.

Developmental and Behavioral Pediatric Department & Child Primary Care Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and MOE- Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Bumetanide has been reported to alter synaptic excitation-inhibition (E-I) balance by potentiating the action of γ-aminobutyric acid (GABA), thereby attenuating the severity of autism spectrum disorder (ASD) in animal models. However, clinical evidence of its efficacy in young patients with ASD is limited. This was investigated in the present clinical trial of 83 patients, randomised to the bumetanide group (bumetanide treatment, 0.5 mg twice daily) or the control group (no bumetanide treatment). Primary [Children Autism Rating Scale (CARS)], secondary [Clinical Global Impressions (CGI)], and exploratory [inhibitory (γ-aminobutyric acid, GABA) and excitatory (glutamate, Glx) neurotransmitter concentrations measured in the insular cortex (IC) and visual cortex (VC) by magnetic resonance spectroscopy (MRS)] outcome measures were evaluated at baseline and at the 3-month follow-up. Side effects were monitored throughout the treatment course. Compared with the control group, the bumetanide group showed significant reduction in symptom severity, as indicated by both total CARS score and number of items assigned a score ≥ 3. The improvement in clinical symptoms was confirmed by CGI. GABA/Glx ratio in both the IC and VC decreased more rapidly over the 3-month period in the bumetanide group than that in the control group. This decrease in the IC was associated with the symptom improvement in the bumetanide group. Our study confirmed the clinical efficacy of bumetanide on alleviating the core symptoms of ASD in young children and it is the first demonstration that the improvement is associated with reduction in GABA/Glx ratios. This study suggests that the GABA/Glx ratio measured by MRS may provide a neuroimaging biomarker for assessing treatment efficacy for bumetanide.
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http://dx.doi.org/10.1038/s41398-020-0692-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026137PMC
January 2020

Probabilistic reversal learning under acute tryptophan depletion in healthy humans: a conventional analysis.

J Psychopharmacol 2020 05 18;34(5):580-583. Epub 2020 Feb 18.

Department of Psychology, University of Cambridge, Cambridge, UK.

The involvement of serotonin in responses to negative feedback is well established. Acute serotonin reuptake inhibition has enhanced sensitivity to negative feedback (SNF), modelled by behaviour in probabilistic reversal learning (PRL) paradigms. Whilst experiments employing acute tryptophan depletion (ATD) in humans, to reduce serotonin synthesis, have shown no clear effect on SNF, sample sizes have been small. We studied a large sample of healthy volunteers, male and female, and found ATD had no effect on core behavioural measures in PRL. These results indicate that ATD effects can differ from other manipulations of serotonin expected to have a parallel or opposing action.
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http://dx.doi.org/10.1177/0269881120907991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222282PMC
May 2020

Psychometric Properties and Validation of the EMOTICOM Test Battery in a Healthy Danish Population.

Front Psychol 2019 3;10:2660. Epub 2019 Dec 3.

Neurobiology Research Unit, The Neuroscience Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

Disruptions in hot cognition, i.e., the processing of emotionally salient information, are prevalent in most neuropsychiatric disorders and constitute a potential treatment target. EMOTICOM is the first comprehensive neuropsychological test battery developed specifically to assess hot cognition. The aim of the study was to validate and establish a Danish language version and reference data for the EMOTICOM test battery. To evaluate the psychometric properties of 11 EMOTICOM tasks, we collected data from 100 healthy Danish participants (50 males, 50 females) including retest data from 49 participants. We assessed test-retest reliability, floor and ceiling effects, task-intercorrelations, and correlations between task performance and relevant demographic and descriptive factors. We found that test-retest reliability varied from poor to excellent while some tasks exhibited floor or ceiling effects. Intercorrelations among EMOTICOM task outcomes were low, indicating that the tasks capture different cognitive constructs. EMOTICOM task performance was largely independent of age, sex, education, and IQ as well as current mood, personality, and self-reported motivation and diligence during task completion. Overall, many of the EMOTICOM tasks were found to be useful and objective measures of hot cognition although select tasks may benefit from modifications to avoid floor and ceiling effects in healthy individuals.
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http://dx.doi.org/10.3389/fpsyg.2019.02660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901831PMC
December 2019

Are candidate neurocognitive endophenotypes of OCD present in paediatric patients? A systematic review.

Neurosci Biobehav Rev 2020 01 9;108:617-645. Epub 2019 Dec 9.

Behavioural and Clinical Neuroscience Institute, University of Cambridge, CB2 3EL, Cambridge, UK; Department of Psychology, Downing Site, University of Cambridge, CB2 3EB, Cambridge, UK. Electronic address:

To-date it has been difficult to ascertain the exact cognitive profile of childhood OCD as studies report variable results. Adult OCD research lately utilises the endophenotype approach; studying cognitive traits that are present in both patients and their unaffected first-degree relatives, and are thought to lie closer to the genotype than the full-blown disorder. By observing whether candidate endopenotypes of adult OCD are present in child patients, we can determine whether the two subtypes show cognitive overlap. We conducted a systematic review of the paediatric OCD literature focussing on proposed neurocognitive endophenotypes of OCD: cognitive flexibility, response inhibition, memory, planning, decision-making, action monitoring, and reversal learning. We found that paediatric patients present robust increases in brain error related negativity associated with abnormal action monitoring, impaired decision-making under uncertainty, planning, and visual working memory, but there is less evidence for deficits in other cognitive domains. This implies that children with OCD show some cognitive similarities with adult patients, but other dysfunctions may only manifest later in the disorder trajectory.
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http://dx.doi.org/10.1016/j.neubiorev.2019.12.010DOI Listing
January 2020

Inhibition-Related Cortical Hypoconnectivity as a Candidate Vulnerability Marker for Obsessive-Compulsive Disorder.

Biol Psychiatry Cogn Neurosci Neuroimaging 2020 02 16;5(2):222-230. Epub 2019 Oct 16.

Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom. Electronic address:

Background: Obsessive-compulsive disorder (OCD) is a prevalent neuropsychiatric condition, with biological models implicating disruption of cortically mediated inhibitory control pathways, ordinarily serving to regulate our environmental responses and habits. The aim of this study was to evaluate inhibition-related cortical dysconnectivity as a novel candidate vulnerability marker of OCD.

Methods: In total, 20 patients with OCD, 18 clinically asymptomatic first-degree relatives of patients with OCD, and 20 control participants took part in a neuroimaging study comprising a functional magnetic resonance imaging stop signal task. Brain activations during the contrasts of interest were cluster thresholded, and a three-dimensional watershed algorithm was used to decompose activation maps into discrete clusters. Functional connections between these key neural nodes were examined using a generalized psychophysiological interaction model.

Results: The three groups did not differ in terms of age, education level, gender, IQ, or behavioral task parameters. Patients with OCD exhibited hyperactivation of the bilateral occipital cortex during the task versus the other groups. Compared with control participants, patients with OCD and their relatives exhibited significantly reduced connectivity between neural nodes, including frontal cortical, middle occipital cortical, and cerebellar regions, during the stop signal task.

Conclusions: These findings indicate that hypoconnectivity between anterior and posterior cortical regions during inhibitory control represents a candidate vulnerability marker for OCD. Such vulnerability markers, if found to generalize, may be valuable to shed light on etiological processes contributing not only to OCD but also obsessive-compulsive-related disorders more widely.
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http://dx.doi.org/10.1016/j.bpsc.2019.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003031PMC
February 2020