Biology subjects

Dolan, R. J.

Publications and source records attributed to Dolan, R. J..

6 recordsLinked to original sources

bioRxiv2018

Compulsivity and impulsivity are linked to distinct aberrant developmental trajectories of fronto-striatal myelination

The transition from adolescence into adulthood is a period where rapid brain development coincides with an enhanced incidence of psychiatric disorder. The precise developmental brain changes that account for this emergent psychiatric symptomatology remain obscure. Capitalising on a unique longitudinal dataset, that includes in-vivo myelin-sensitive magnetization transfer (MT) MRI, we show this transition period is characterised by brain-wide growth in MT, within both gray matter and adjacent juxta-cortical white matter. We show that an expression of common developmental psychiatric risk symptomatology in this otherwise healthy population, specifically compulsivity and impulsivity, is tied to regionally specific aberrant unfolding of these MT trajectories. This is most marked in frontal midline structures for compulsivity, and in lateral frontal areas for impulsivity. The findings highlight a brain developmental linkage for emergent psychiatric risk features, evident in regionally specific perturbations in the expansion of MT-related myelination.

neuroscience↗

bioRxiv2018

Noradrenaline modulates decision urgency during sequential information gathering

Arbitrating between timely choice and extended information gathering is critical in effective decision making. Aberrant information gathering behaviour is said to be a feature of psychiatric disorders such as schizophrenia and obsessive-compulsive disorder. We know little about the neurocognitive control mechanisms that drive such information gathering. In a double-blind placebo-controlled drug study with 60 healthy humans (30 female), we examined the effects of noradrenaline and dopamine antagonism on information gathering. We show that modulating noradrenaline function with propranolol leads to decreased information gathering behaviour and this contrasts with no effect following a modulation of dopamine function. Using a Bayesian computational model, we show sampling behaviour is best explained when including an urgency signal that promotes commitment to an early decision. We demonstrate that noradrenaline blockade promotes the expression of this decision-related urgency signal during information gathering. We discuss the findings with respect to psychopathological conditions that are linked to aberrant information gathering.\n\nSignificance StatementKnowing when to stop gathering information and commit to an option is non-trivial. This is an important element in arbitrating between information gain and energy conservation. In this double-blind, placebo-controlled drug study, we investigated to role of catecholamines noradrenaline and dopamine on sequential information gathering. We found that blocking noradrenaline led to a decrease in information gathering, with no effect seen following dopamine blockade. Using a Bayesian computational model, we show that this noradrenaline effect is driven by an increased decision urgency, a signal that reflects an escalating subjective cost of sampling. The observation that noradrenaline modulates decision urgency suggests new avenues for treating patients that show information gathering deficits.

neuroscience↗

bioRxiv2017

Value Encoding in the Globus Pallidus: fMRI reveals an interaction effect between reward and dopamine drive

The external part of the globus pallidus (GPe) is a core nucleus of the basal ganglia (BG) whose activity is disrupted under conditions of low dopamine release, as in Parkinsons disease. Current models assume decreased dopamine release in the dorsal striatum results in deactivation of dorsal GPe, which in turn affects motor expression via a regulatory effect on other nuclei of the BG. However, recent studies in healthy and pathological animal models have reported neural dynamics that do not match with this view of the GPe as a relay in the BG circuit. Thus, the computational role of the GPe in the BG is still to be determined. We previously proposed a neural model that revisits the functions of the nuclei of the BG, and this model predicts that GPe encodes values which are amplified under a condition of low striatal dopaminergic drive. To test this prediction, we used an fMRI paradigm involving a within-subject placebo-controlled design, using the dopamine antagonist risperidone, wherein healthy volunteers performed a motor selection and maintenance task under low and high reward conditions. ROI-based fMRI analysis revealed an interaction between reward and dopamine drive manipulations, with increased BOLD activity in GPe in a high compared to low reward condition, and under risperidone compared to placebo. These results confirm the core prediction of our computational model, and provide a new perspective on neural dynamics in the BG and their effects on motor selection and motor disorders.

neuroscience↗

bioRxiv2017

Morphometric Similarity Networks Detect Microscale Cortical Organisation And Predict Inter-Individual Cognitive Variation

Macroscopic cortical networks are important for cognitive function, but it remains challenging to construct anatomically plausible individual structural connectomes from human neuroimaging. We introduce a new technique for cortical network mapping, based on inter-regional similarity of multiple morphometric parameters measured using multimodal MRI. In three cohorts (two human, one macaque), we find that the resulting morphometric similarity networks (MSNs) have a complex topological organisation comprising modules and high-degree hubs. Human MSN modules recapitulate known cortical cytoarchitectonic divisions, and greater inter-regional morphometric similarity was associated with stronger inter-regional co-expression of genes enriched for neuronal terms. Comparing macaque MSNs to tract-tracing data confirmed that morphometric similarity was related to axonal connectivity. Finally, variation in the degree of human MSN nodes accounted for about 40% of between-subject variability in IQ. Morphometric similarity mapping provides a novel, robust and biologically plausible approach to understanding how human cortical networks underpin individual differences in psychological functions.

neuroscience↗

bioRxiv2017

A lineage-related reciprocal inhibition circuitry for sensory-motor action selection

The insect central complex and vertebrate basal ganglia are forebrain centres involved in selection and maintenance of behavioural actions. However, little is known about the formation of the underlying circuits, or how they integrate sensory information for motor actions. Here, we show that paired embryonic neuroblasts generate central complex ring neurons that mediate sensory-motor transformation and action selection in Drosophila. Lineage analysis resolves four ring neuron subtypes, R1-R4, that form GABAergic inhibition circuitry among inhibitory sister cells. Genetic manipulations, together with functional imaging, demonstrate subtype-specific R neurons mediate the selection and maintenance of behavioural activity. A computational model substantiates genetic and behavioural observations suggesting that R neuron circuitry functions as salience detector using competitive inhibition to amplify, maintain or switch between activity states. The resultant gating mechanism translates facilitation, inhibition and disinhibition of behavioural activity as R neuron functions into selection of motor actions and their organisation into action sequences.

neuroscience↗

bioRxiv2017

Metacognitive impairments extend perceptual decision making weaknesses in compulsivity

Awareness of ones own abilities is of paramount importance in adaptive decision making. Psychotherapeutic theories assume such metacognitive insight is impaired in compulsivity, though this is supported by scant empirical evidence. In this study, we investigate metacognitive abilities in compulsive participants using computational models, where these enable a segregation between metacognitive and perceptual decision making impairments. We examined twenty low-compulsive and twenty high-compulsive participants, recruited from a large population-based sample, and matched for other psychiatric and cognitive dimensions. Hierarchical computational modelling of the participants metacognitive abilities on a visual global motion detection paradigm revealed that high-compulsive participants had a reduced metacognitive ability. This impairment was accompanied by a perceptual decision making deficit whereby motion-related evidence was accumulated more slowly in high compulsive participants. Our study shows that the compulsivity spectrum is associated with a reduced ability to monitor ones own performance, over and above any perceptual decision making difficulty.

neuroscience↗