Matthew Nour

University of Oxford | OX · Department of Psychiatry

Structured internal representations (cognitive maps) shape cognition, from imagining the future and counterfactual past, to transferring knowledge to new settings. Our understanding of how such representations are formed and maintained in biological and artificial neural networks has grown enormously. The cognitive mapping hypothesis of schizophren...

Mitochondrial complex I is the largest enzyme complex in the respiratory chain and can be non-invasively measured using [18F]BCPP-EF positron emission tomography (PET). Neurological conditions associated with mitochondria complex I pathology are also associated with altered blood oxygen level dependent (BOLD) response and impairments in cognition....

Synaptic terminal density is thought to influence cognitive function and neural activity, yet its role in cognition has not been explored in healthy humans. We examined these relationships using [11C]UCB-J positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) in 25 healthy adults performing cognitive function tasks in...

Background The histamine-3 receptor (H3R) may have a role in cognitive processes, through its action as a presynaptic heteroreceptor inhibiting the release of glutamate in the brain. To explore this, we examined anterior cingulate cortex (ACC) and striatum H3R availability in patients with schizophrenia, and characterised their relationships with g...

Aim Psychedelics have recently gained attention as potential therapeutic agents for various psychiatric disorders. Previous research has highlighted that a diminished sense of self, commonly termed “ego‐dissolution” is a pivotal feature of the psychedelic‐induced state. While the Ego‐Dissolution Inventory (EDI) is a widely acknowledged instrument f...

Human cognition is underpinned by structured internal representations that encode relationships between entities in the world (cognitive maps). Clinical features of schizophrenia—from thought disorder to delusions—are proposed to reflect disorganization in such conceptual representations. Schizophrenia is also linked to abnormalities in neural proc...

Background: Reward processing deficits are a core feature of schizophrenia and are thought to underlie negative symptoms. Pre-clinical evidence suggests that opioid neurotransmission is linked to reward processing. However, the contribution of Mu Opioid Receptor (MOR) signalling to the reward processing abnormalities in schizophrenia is unknown. H...

Background: The histamine-3 receptor (H3R) is an auto- and heteroreceptor that inhibits the release of histamine and other neurotransmitters. Post-mortem evidence has found altered H3R expression in patients with psychotic disorders, which may underlie cognitive impairment associated with schizophrenia (CIAS). Aims: We used positron emission tom...

Mystical experiences and ego dissolution are essential to understanding the lasting psychological effects of psychedelics or even natural religious experience. The main objective of the article is to present evidence of construct validity in the adaptation to Brazilian Portuguese of the Hood Mysticism Scale (HMS) and the Ego-Dissolution Inventory (...

The neuromodulator dopamine and excitatory neurotransmitter glutamate have both been implicated in the pathogenesis of psychosis, and dopamine antagonists remain the predominant treatment for psychotic disorders. To date no study has measured the effect of antipsychotics on both of these indices together, in the same population of people with psych...

Schizophrenia is characterised by abnormal resting state and default mode network (DMN) brain activity. However, despite intense study, the mechanisms linking DMN dynamics to neural computation remain elusive. During rest, sequential hippocampal reactivations, known as ‘replay’, are played out within DMN activation windows, highlighting a potential...

Background Cardiovascular disease is a major cause of excess mortality in people with schizophrenia. Several factors are responsible, including lifestyle and metabolic effects of antipsychotics. However, variations in cardiac structure and function are seen in people with schizophrenia in the absence of cardiovascular disease risk factors and after...

The pathophysiology of schizophrenia involves abnormal reward processing, thought to be due to disrupted striatal and dopaminergic function. Consistent with this hypothesis, functional magnetic resonance imaging (fMRI) studies using the monetary incentive delay (MID) task report hypoactivation in the striatum during reward anticipation in schizophr...

Introduction Glutamatergic dysfunction is implicated in the pathophysiology of schizophrenia. It is unclear whether glutamatergic dysfunction predicts response to treatment or if antipsychotic treatment influences glutamate levels. We investigated the effect of antipsychotic treatment on glutamatergic levels in the anterior cingulate cortex (ACC),...

Rationale A general feeling of disconnection has been associated with mental and emotional suffering. Improvements to a sense of connectedness to self, others and the wider world have been reported by participants in clinical trials of psychedelic therapy. Such accounts have led us to a definition of the psychological construct of ‘connectedness’ a...

Psychiatric disorders encompass complex aberrations of cognition and affect and are among the most debilitating and poorly understood of any medical condition. Current treatments rely primarily on interventions that target brain function (drugs) or learning processes (psychotherapy). A mechanistic understanding of how these interventions mediate th...

Background and hypotheses Hippocampal replay and associated high-frequency ripple oscillations are among the best characterised phenomena in resting brain activity. Replay/ripples support memory consolidation and relational inference, and are regulated by N-methyl-D-aspartate receptors (NMDARs). Schizophrenia has been associated with both replay/ri...

Prefrontal cortex has been shown to regulate striatal dopaminergic function via glutamatergic mechanisms in preclinical studies. Concurrent disruption of these systems is also often seen in neuropsychiatric disease. The simultaneous measurement of striatal dopamine signaling, cortical gray matter, and glutamate levels is therefore of major interest...

An ability to build structured cognitive maps of the world may lie at the heart of understanding cognitive features of schizophrenia. In rodents, cognitive map representations are supported by sequential hippocampal place cell reactivations during rest (offline), known as replay. These events occur in the context of local high frequency ripple osci...

In human neuroscience, studies of cognition are rarely grounded in non-task-evoked, ‘spontaneous’ neural activity. Indeed, studies of spontaneous activity tend to focus predominantly on intrinsic neural patterns (for example, resting-state networks). Taking a ‘representation-rich’ approach bridges the gap between cognition and resting-state communi...

Introduction Q.Clear is a Bayesian penalised likelihood (BPL) reconstruction algorithm available on General Electric (GE) Positron Emission Tomography (PET)-Computed Tomography (CT) and PET-Magnetic Resonance (MR) scanners. This algorithm is regulated by a β value which acts as a noise penalisation factor and yields improvements in signal to noise...

Dopamine signaling is constrained to discrete tracts yet has brain-wide effects on neural activity. The nature of this relationship between local dopamine signaling and brain-wide neuronal activity is not clearly defined and has relevance for neuropsychiatric illnesses where abnormalities of cortical activity and dopamine signaling coexist. Using s...

An ability to build structured mental maps of the world underpins our capacity to imagine relationships between objects that extend beyond experience. In rodents, such representations are supported by sequential place cell reactivations during rest, known as replay. Schizophrenia is proposed to reflect a compromise in structured mental representati...

Background: Clozapine is the only effective medication for treatment-resistant schizophrenia; however, its mechanism of action remains unclear. The present study explored whether its effectiveness is related to changes in hematological measures after clozapine initiation. Methods: Patients with treatment-resistant schizophrenia commenced on cloz...

Background Striatal dopamine dysfunction is proposed to underlie symptoms in psychosis, yet it is not known how changes in a single neurotransmitter could underlie the heterogenous presentations that are seen clinically. One hypothesis is that the symptomatic consequences of aberrant dopamine signalling may depend on where within the striatum dysfu...

Background Striatal dopamine dysfunction is thought to underlie symptoms in psychosis, yet it remains unclear how a single neurotransmitter could cause the diverse presentations that are observed clinically. One hypothesis is that the consequences of aberrant dopamine signalling vary depending on where within the striatum the dysfunction occurs. Po...

Choosing actions that result in advantageous outcomes is a fundamental function of nervous systems. All computational decision-making models contain a mechanism that controls the variability of (or confidence in) action selection, but its neural implementation is unclear-especially in humans. We investigated this mechanism using two influential dec...

Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N-Dimethyltryptamine (DMT - a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal div...

Childhood trauma is a risk factor for psychosis. Amphetamine increases synaptic striatal dopamine levels and can induce positive psychotic symptoms in healthy individuals and patients with schizophrenia. Socio-developmental hypotheses of psychosis propose that childhood trauma and other environmental risk factors sensitize the dopamine system to in...

Psychotic illnesses show variable responses to treatment. Determining the neurobiology underlying this is important for precision medicine and the development of better treatments. It has been proposed that dopaminergic differences underlie variation in response, with striatal dopamine synthesis capacity (DSC) elevated in responders and unaltered i...

Studying transitions in and out of the altered state of consciousness caused by intravenous (IV) N,N- Dimethyltryptamine (DMT - a fast-acting tryptamine psychedelic) offers a safe and powerful means of advancing knowledge on the neurobiology of conscious states. Here we sought to investigate the effects of IV DMT on the power spectrum and signal di...

Working memory performance is thought to depend on both striatal dopamine 2/3 receptors (D2/3Rs) and task-induced functional organisation in key cortical brain networks. Here, we combine functional magnetic resonance imaging and D2/3R positron emission tomography in 51 healthy volunteers, to investigate the relationship between working memory perfo...

The Disrupted‐in‐Schizophrenia 1 (DISC1) protein has been implicated in a range of biological mechanisms underlying chronic mental disorders such as schizophrenia. Schizophrenia is associated with abnormal striatal dopamine signalling, and all antipsychotic drugs block striatal dopamine 2/3 receptors (D2/3Rs). Importantly, the DISC1 protein directl...

Background Glutamatergic dysfunction is implicated in the pathophysiology of schizophrenia, with studies reporting elevated glutamatergic metabolites across brain regions of patients. There is consistent evidence showing a decrease in glutamate metabolites after antipsychotic administration. However, the literature on the relationship between the g...

Significance To survive in changing environments animals must use sensory information to form accurate representations of the world. Surprising sensory information might signal that our current beliefs about the world are inaccurate, motivating a belief update. Here, we investigate the neuroanatomical and neurochemical mechanisms underlying the bra...

BACKGROUND: A wide range of neuropsychiatric disorders, from schizophrenia to drug addiction, involve abnormalities in both the mesolimbic dopamine system and the cortical salience network. Both systems play a key role in the detection of behaviorally relevant environmental stimuli. Although anatomical overlap exists, the functional relationship be...

Background: The pathophysiology of psychosis is incompletely understood. Disruption in cortical glutamatergic signalling causing aberrant striatal dopamine synthesis capacity is a proposed model for psychosis, but has not been tested in vivo. We therefore aimed to test the relationship between cortical glutamate concentrations and striatal dopamin...

Background: A wide range of neuropsychiatric disorders, from schizophrenia to drug addiction, involve abnormalities in both the mesolimbic dopamine system and the cortical salience network. Both systems play a key role in the detection of behaviorally relevant environmental stimuli. Although anatomical overlap exists, the functional relationship b...

Classical views of the medial temporal lobe (MTL) have established that it plays a crucial role in long‐term memory (LTM) (e.g. Scoville and Milner, 1957). Here we demonstrate, in a sample of patients who have undergone anterior temporal lobectomy for the treatment of epilepsy, that the MTL additionally plays a specific, causal role in short‐term m...

Background: Elevated striatal dopamine synthesis capacity has been implicated in the etiology and antipsychotic response in psychotic illness. The effects of antipsychotic medication on dopamine synthesis capacity are poorly understood, and no prospective studies have examined this question in a solely first-episode psychosis sample. Furthermore,...

Dubiety exists over whether clinical symptoms of schizophrenia can be distinguished from affective psychosis, the assumption being that absence of a "point of rarity" indicates lack of nosological distinction, based on prior group-level analyses. Advanced machine learning techniques, using unsupervised (hierarchical clustering) and supervised (regu...

Objective To explore whether psilocybin with psychological support modulates personality parameters in patients suffering from treatment‐resistant depression (TRD). Method Twenty patients with moderate or severe, unipolar, TRD received oral psilocybin (10 and 25 mg, one week apart) in a supportive setting. Personality was assessed at baseline and...

Background The aberrant salience hypothesis of schizophrenia proposes that symptoms such as paranoia arise when behavioural salience is attributed to neutral stimuli. Mesolimbic dopamine dysfunction is thought to be central to this mechanism; building on findings that activity in this pathway conveys a (signed) reward prediction error signal. Given...

Background The dopamine hypothesis of psychosis suggests that dopamine abnormalities are present in psychotic illness, irrespective of diagnostic class. Meta-analyses of Positron Emission Tomography (PET) studies of the dopamine system have shown elevated dopamine synthesis capacity in schizophrenia, though there is a dearth of studies examining th...

Dopamine may be critical for processing the meaningful information content of observations, which drives belief updating about the (hidden) states of the world [1–3]. In human functional magnetic resonance imaging (fMRI) studies, neuronal activity encoding the magnitude of belief updates has been detected in dopamine-rich midbrain regions, namely t...

Importance The dopamine hypothesis suggests that dopamine abnormalities underlie psychosis, irrespective of diagnosis, implicating dopamine dysregulation in bipolar affective disorder and schizophrenia, in line with the research domain criteria approach. However, this hypothesis has not been directly examined in individuals diagnosed with bipolar d...

The psychedelic experience (including psychedelic-induced ego dissolution) can effect lasting change in a person's attitudes and beliefs. Here, we aimed to investigate the association between naturalistic psychedelic use and personality, political perspectives, and nature relatedness using an anonymous internet survey. Participants (N = 893) provid...

Surfing Uncertainty: Prediction, Action, and the Embodied Mind By Andy Clark Oxford University Press. 2016. £19.99 (hb). 424 pp. ISBN 9780190217013 Our understanding of ‘how the brain works’ has expanded enormously in recent decades. Nevertheless, the relatively new field of neuroscience is

Bipolar affective disorder is a common neuropsychiatric disorder. Although its neurobiological underpinnings are incompletely understood, the dopamine hypothesis has been a key theory of the pathophysiology of both manic and depressive phases of the illness for over four decades. The increased use of antidopaminergics in the treatment of this disor...

Altered self-experiences arise in certain psychiatric conditions, and may be induced by psychoactive drugs and spiritual/religious practices. Recently, a neuroscience of self-experience has begun to crystallise, drawing upon findings from functional neuroimaging and altered states of consciousness occasioned by psychedelic drugs. This advance may b...

Background: Antipsychotic medication remains the primary treatment for symptoms of psychosis. The dopamine system, in particular, the presynaptic system, has been linked to treatment response, leading to the suggestion that dopaminergic and nondopaminergic forms of schizophrenia exist. This has been examined in vivo, using PET to index presynaptic...

Objective: YouTube ( www.youtube.com ) is the most popular video-sharing Web site on the Internet and is used by medical students as a source of information regarding mental health conditions, including schizophrenia. The accuracy and educational utility of schizophrenia presentations on YouTube are unknown. The purpose of this study was to analyz...

Waking Up: Searching for Spirituality without Religion Sam Harris Bantam Press, 2014, £20, hb, 245 pp. ISBN: 9780593074015 Sam Harris has been waiting to write this book for over a decade. This may surprise some. The subject matter – dealing reverently with human spiritual experience – is at

The nature of perception has fascinated philosophers for centuries, and has more recently been the focus of research in psychology and neuroscience. Many psychiatric disorders are characterised by perceptual abnormalities, ranging from sensory distortions to illusions and hallucinations. The distinction between normal and abnormal perception is, ho...

Aims: The experience of a compromised sense of “self”, termed ego-dissolution, is a key feature of the psychedelic experience. This study aimed to validate the Ego-Dissolution Inventory (EDI), a new 8-item self-report scale designed to measure ego-dissolution. Additionally, we aimed to investigate the specificity of the relationship between psyched...

Objective: To investigate the association between neuromyelitis optica spectrum disorder (NMOSD) and pregnancy outcome. Methods: An international cohort of women with aquaporin-4 antibody-positive NMOSD and ≥1 pregnancy was studied retrospectively. Multivariate logistic regression was used to investigate whether pregnancy after NMOSD onset was a...

Descriptive psychopathology makes a distinction between veridical perception and illusory perception. In both cases a perception is tied to a sensory stimulus, but in illusions the perception is of a false object. This article re-examines this distinction in light of new work in theoretical and computational neurobiology, which views all perception...

In a recent issue of PNAS, Douaud et al. (1) identify a transmodal network of brain areas (IC4) that show an “inverted-U” relationship between age and gray matter volume. These findings lend support to the “last in, first out” hypothesis, whereby phylogenetically recent cortical regions mature later, and degenerate earlier, than other brain regions...

We welcome the renewed interest in the therapeutic potential of psychedelic compounds. In their recent editorial, Sessa & Johnson[1][1] echo the fervent research climate of psychedelics spanning the 1950s and ’60s. They suggest that psychedelics may cause prolonged changes in participants’

A number of recent articles, many appearing in Schizophrenia Bulletin, signal a renewed interest in phenomenological approaches to our understanding of schizophrenia. These approaches conceptualize schizophrenia as a disorder of altered self-awareness and decreased prereflective social attunement, which may manifest as an impaired understanding of...

Objective Neuromyelitis Optica Spectrum Disorder (NMOSD) predominantly affects women and is often active during childbearing years. We investigated the association between NMOSD and pregnancy outcome. Methods Multivariate logistic regression was used to investigate whether pregnancies after NMOSD onset were at an increased risk of miscarriage or pr...