radiotracer-administration-for-high-temporal-resolution-positron

Radiotracer Administration for High Temporal Resolution Positron Emission Tomography of the Human Brain: Application to FDG-fPET

Functional positron emission tomography (fPET) provides a method to track molecular targets in the human brain. With a radioactively-labelled glucose ...

Monash University

Magnetoencephalography was used to examine the effect on the N400m of reading words that create emotional violations in sentences. The beginnings of the sentences were affectively negative and were completed with either a negative congruous, positive incongruous, or neutral incongruous adjective (e.g., "My mother was killed and I felt bad/great/normal"). The task conditions were also manipulated to favor semantic over affective processing. Compared to the sentences with the congruous negative adjectives, the results of sensor space analysis showed that there was an N400m effect with the sentences with the neutral but not positive adjectives, despite both types of sentences containing an emotional violation. Source localization results showed a similar pattern where the sentences with the incongruous positive versus congruous negative adjectives showed no significant N400m effect in the temporal and frontal areas examined, but the sentences with the incongruous neutral versus incongruous positive adjectives in the temporal areas did, particularly the left middle temporal gyrus. These results suggest that (a) the N400m effect was likely to be caused by the incongruous neutral adjectives being comparatively harder to integrate into a negative emotional context than the incongruous positive ones, (b) emotional context created by the negative sentence stems caused deeper semantic processing of the incongruous positive adjectives to be bypassed, and (c) negative affective context was generated from reading the sentences even in task conditions where it has not been generated with isolated words. 

Examining the N400m in affectively negative sentences: A magnetoencephalography study.

Dysfunction of corticostriatal loops has been proposed to underlie certain cognitive and behavioral problems associated with various neuropsychiatric disorders, such as obsessive-compulsive disorder (OCD) characterized by repetitive, unwanted thoughts, and behaviors. Although functional abnormalities in the loops involving the orbitofronto-striato-thalamic (OFST) circuitry in patients with OCD have been reported, our understanding of a link between disruptions in the architecture of the intrinsic functional network of the OFST circuit and their symptoms remain incomplete. Using resting-state functional MRI in conjunction with unsupervised clustering and multilevel functional connectivity (FC) techniques, FC of the OFST network and its topological organization in 61 OCD patients versus 61 matched controls were characterized. Patients exhibited disruptions in small-world properties of the OFST circuit, which indicates an imbalance between functional integration and segregation. Patients also showed decreased FC between the central orbitofrontal cortex and dorsomedial striatum but increased FC between the medial thalamus and striatal areas. Using one of the largest samples of unmedicated OCD patients to date, our findings provide evidence supporting the OFST dysconnection hypothesis in OCD as a basic pathophysiological mechanism underlying the disorder, showing the disruption of FC between specific cortical, striatal, and thalamic clusters and aberrant topological patterns of the OFST circuit. Hum Brain Mapp 38:109-119, 2017. © 2016 Wiley Periodicals, Inc.

Altered functional network architecture in orbitofronto-striato-thalamic circuit of unmedicated patients with obsessive-compulsive disorder.

Systematic Overestimation of Reflection Impulsivity in the Information Sampling Task.

The occurrence of repetitive behaviours that are often harmful has been attributed to traits traditionally described as "impulsive" or "compulsive" e.g. substance dependence, excessive gambling, and hoarding. These behaviours are common and often co-occur in both the general population and psychiatric populations. The lack of measures to concurrently index a range of such behaviours led to the development of the Impulsive-Compulsive Behaviours (ICB) Checklist. This study aims to validate the ICB Checklist in a general community sample. Factor analyses revealed a two-factor structure, demonstrating good model fit in two independent samples. These were labelled Impulsive-Compulsions and Compulsive-Impulsions, comprising of classically compulsive and impulsive behaviours respectively. Reliability and construct validity were further confirmed using correlations with existing measures of impulsivity and compulsivity. Results suggest that the ICB Checklist is a valid and practical assessment that can be used to monitor behavioural clusters characterised by deficits in inhibition.

A psychometric validation study of the Impulsive-Compulsive Behaviours Checklist: A transdiagnostic tool for addictive and compulsive behaviours.

Neuroscientific explanations of gambling disorder can help people make sense of their experiences and guide the development of psychosocial interventions. However, the societal perceptions and implications of these explanations are not always clear or helpful. Two workshops in 2013 and 2014 brought together multidisciplinary researchers aiming to improve the clinical and policy-related effects of neuroscience research on gambling. The workshops revealed that neuroscience can be used to improve identification of the dangers of products used in gambling. Additionally, there was optimism associated with the diagnostic and prognostic uses of neuroscience in problem gambling and the provision of novel tools (eg, virtual reality) to assess the effectiveness of new policy interventions before their implementation. Other messages from these workshops were that neuroscientific models of decision making could provide a strong rationale for precommitment strategies and that interdisciplinary collaborations are needed to reduce the harms of gambling.

Neuroscience in gambling policy and treatment: an interdisciplinary perspective.

We aimed to determine whether individuals with obsessive-compulsive disorder (OCD) and demographically matched healthy individuals can be clustered into distinct clinical subtypes based on dimensional measures of their self-reported compulsivity (OBQ-44 and IUS-12) and impulsivity (UPPS-P).

Unpacking the role of self-reported compulsivity and impulsivity in obsessive-compulsive disorder.

Estimates of functional connectivity derived from resting-state functional magnetic resonance imaging (rs-fMRI) are sensitive to artefacts caused by in-scanner head motion. This susceptibility has motivated the development of numerous denoising methods designed to mitigate motion-related artefacts. Here, we compare popular retrospective rs-fMRI denoising methods, such as regression of head motion parameters and mean white matter (WM) and cerebrospinal fluid (CSF) (with and without expansion terms), aCompCor, volume censoring (e.g., scrubbing and spike regression), global signal regression and ICA-AROMA, combined into 19 different pipelines. These pipelines were evaluated across five different quality control benchmarks in four independent datasets associated with varying levels of motion. Pipelines were benchmarked by examining the residual relationship between in-scanner movement and functional connectivity after denoising; the effect of distance on this residual relationship; whole-brain differences in functional connectivity between high- and low-motion healthy controls (HC); the temporal degrees of freedom lost during denoising; and the test-retest reliability of functional connectivity estimates. We also compared the sensitivity of each pipeline to clinical differences in functional connectivity in independent samples of people with schizophrenia and obsessive-compulsive disorder. Our results indicate that (1) simple linear regression of regional fMRI time series against head motion parameters and WM/CSF signals (with or without expansion terms) is not sufficient to remove head motion artefacts; (2) aCompCor pipelines may only be viable in low-motion data; (3) volume censoring performs well at minimising motion-related artefact but a major benefit of this approach derives from the exclusion of high-motion individuals; (4) while not as effective as volume censoring, ICA-AROMA performed well across our benchmarks for relatively low cost in terms of data loss; (5) the addition of global signal regression improved the performance of nearly all pipelines on most benchmarks, but exacerbated the distance-dependence of correlations between motion and functional connectivity; and (6) group comparisons in functional connectivity between healthy controls and schizophrenia patients are highly dependent on preprocessing strategy. We offer some recommendations for best practice and outline simple analyses to facilitate transparent reporting of the degree to which a given set of findings may be affected by motion-related artefact.

An evaluation of the efficacy, reliability, and sensitivity of motion correction strategies for resting-state functional MRI.

The concept of "food addiction" (FA) has gained popularity in view of clinical and neurobiological overlaps between excessive food intake and addictive disorders. However, no studies have examined the link between FA and striatocortical circuits involved in addictive disorders, or the influence of homeostatic status, which regulates the drive to eat, on these systems. This study aims to investigate changes in striatal functional connectivity between fasted and fed conditions among adults ranging in body mass index (BMI) and FA symptoms.

Food addiction linked to changes in ventral striatum functional connectivity between fasting and satiety.

Impulsivity and compulsivity have been implicated as important transdiagnostic dimensional phenotypes with potential relevance to addiction. We aimed to develop a model that conceptualizes these constructs as overlapping dimensional phenotypes and test whether different components of this model explain the co-occurrence of addictive and related behaviors.

Overlapping dimensional phenotypes of impulsivity and compulsivity explain co-occurrence of addictive and related behaviors.

Aerobic exercise (AE) interventions represent promising therapeutic approaches in disorders that compromise hippocampal integrity, but a more comprehensive account of the neural mechanisms stimulated by AE in the human brain is needed. We conducted a longitudinal pilot-study to assess the impact of a 12-week AE intervention on hippocampal structure and function in 10 healthy, human participants (50% females; 25-59 years). Using a novel combination of multimodal MRI techniques, we found significant increases in left hippocampal volume, Cornu Ammonis subfield area 1, NAA concentration and immediate verbal recall performance. Our preliminary findings highlight the utility of a multimodal approach in assessing hippocampal integrity.

The Influence of Aerobic Exercise on Hippocampal Integrity and Function: Preliminary Findings of a Multi-Modal Imaging Analysis.

Psychotic symptoms are proposed to lie on a continuum, ranging from isolated psychosis-like experiences (PLEs) in nonclinical populations to frank disorder. Here, we investigated the neurobiological correlates of this continuum by examining whether functional connectivity of dorsal corticostriatal circuitry, which is disrupted in psychosis patients and individuals at high risk for psychosis, is associated with the severity of subclinical PLEs.

Functional Connectivity of Corticostriatal Circuitry and Psychosis-like Experiences in the General Community.

Young adulthood is a crucial neurodevelopmental period during which impulsive and compulsive problem behaviours commonly emerge. While traditionally considered diametrically opposed, impulsive and compulsive symptoms tend to co-occur. The objectives of this study were as follows: (a) to identify the optimal trans-diagnostic structural framework for measuring impulsive and compulsive problem behaviours, and (b) to use this optimal framework to identify common/distinct antecedents of these latent phenotypes.

Fractionation of impulsive and compulsive trans-diagnostic phenotypes and their longitudinal associations.

The roles of different nodes within a network are often understood through centrality analysis, which aims to quantify the capacity of a node to influence, or be influenced by, other nodes via its connection topology. Many different centrality measures have been proposed, but the degree to which they offer unique information, and whether it is advantageous to use multiple centrality measures to define node roles, is unclear. Here we calculate correlations between 17 different centrality measures across 212 diverse real-world networks, examine how these correlations relate to variations in network density and global topology, and investigate whether nodes can be clustered into distinct classes according to their centrality profiles. We find that centrality measures are generally positively correlated to each other, the strength of these correlations varies across networks, and network modularity plays a key role in driving these cross-network variations. Data-driven clustering of nodes based on centrality profiles can distinguish different roles, including topological cores of highly central nodes and peripheries of less central nodes. Our findings illustrate how network topology shapes the pattern of correlations between centrality measures and demonstrate how a comparative approach to network centrality can inform the interpretation of nodal roles in complex networks.

Consistency and differences between centrality measures across distinct classes of networks.

Individual differences in impulsivity and compulsivity is thought to underlie vulnerability to a broad range of disorders and are closely tied to cortical-striatal-thalamic-cortical function. However, whether impulsivity and compulsivity in clinical disorders is continuous with the healthy population and explains cortical-striatal-thalamic-cortical dysfunction across different disorders remains unclear. Here, we characterized the relationship between cortical-striatal-thalamic-cortical effective connectivity, estimated using dynamic causal modelling of resting-state functional magnetic resonance imaging data, and dimensional phenotypes of impulsivity and compulsivity in two symptomatically distinct but phenotypically related disorders, obsessive-compulsive disorder and gambling disorder. 487 online participants provided data for modelling of dimensional phenotypes. These data were combined with 34 obsessive-compulsive disorder patients, 22 gambling disorder patients, and 39 healthy controls, who underwent functional magnetic resonance imaging. Three core dimensions were identified: disinhibition, impulsivity, and compulsivity. Patients' scores on these dimensions were continuously distributed with the healthy participants, supporting a continuum model of psychopathology. Across all participants, higher disinhibition correlated with lower bottom-up connectivity in the dorsal circuit and greater bottom-up connectivity in the ventral circuit, and higher compulsivity correlated with lower bottom-up connectivity in the dorsal circuit. In patients, higher clinical severity was also linked to lower bottom-up connectivity in the dorsal circuit, but these findings were independent of phenotypic variation, demonstrating convergence towards behaviourally and clinically relevant changes in brain dynamics. Effective connectivity did not differ as a function of traditional diagnostic labels and only weak associations were observed for functional connectivity measures. Together, our results demonstrate that cortical-striatal-thalamic-cortical dysfunction across obsessive-compulsive disorder and gambling disorder may be better characterized by dimensional phenotypes than diagnostic comparisons, supporting investigation of quantitative liability phenotypes.

Transdiagnostic variations in impulsivity and compulsivity in obsessive-compulsive disorder and gambling disorder correlate with effective connectivity in cortical-striatal-thalamic-cortical circuits.

Article	Year
Examining the N400m in affectively negative sentences: A magnetoencephalography study. Psychophysiology\| PubMed ID: 26787447	2016
Altered functional network architecture in orbitofronto-striato-thalamic circuit of unmedicated patients with obsessive-compulsive disorder. Human brain mapping\| PubMed ID: 27548880	2017
Systematic Overestimation of Reflection Impulsivity in the Information Sampling Task. Biological psychiatry\| PubMed ID: 27587264	2017
A psychometric validation study of the Impulsive-Compulsive Behaviours Checklist: A transdiagnostic tool for addictive and compulsive behaviours. Addictive behaviors\| PubMed ID: 27987424	2017
Neuroscience in gambling policy and treatment: an interdisciplinary perspective. The lancet. Psychiatry\| PubMed ID: 28219609	2017
Unpacking the role of self-reported compulsivity and impulsivity in obsessive-compulsive disorder. CNS spectrums\| PubMed ID: 28487007	2018
An evaluation of the efficacy, reliability, and sensitivity of motion correction strategies for resting-state functional MRI. NeuroImage\| PubMed ID: 29278773	2018
Food addiction linked to changes in ventral striatum functional connectivity between fasting and satiety. Appetite\| PubMed ID: 30312737	2019
Overlapping dimensional phenotypes of impulsivity and compulsivity explain co-occurrence of addictive and related behaviors. CNS spectrums\| PubMed ID: 30458896	2019
The Influence of Aerobic Exercise on Hippocampal Integrity and Function: Preliminary Findings of a Multi-Modal Imaging Analysis. Brain plasticity (Amsterdam, Netherlands)\| PubMed ID: 30598871	2018
Functional Connectivity of Corticostriatal Circuitry and Psychosis-like Experiences in the General Community. Biological psychiatry\| PubMed ID: 30952359	2019
Fractionation of impulsive and compulsive trans-diagnostic phenotypes and their longitudinal associations. The Australian and New Zealand journal of psychiatry\| PubMed ID: 31001986	2019
Consistency and differences between centrality measures across distinct classes of networks. PloS one\| PubMed ID: 31348798	2019
Transdiagnostic variations in impulsivity and compulsivity in obsessive-compulsive disorder and gambling disorder correlate with effective connectivity in cortical-striatal-thalamic-cortical... NeuroImage\| PubMed ID: 31382045	2019

Linden Parkes

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