53 research outputs found
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Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood
Previous research in rodents and humans points to an evolutionarily conserved profle of blunted threat extinction learning during adolescence, underpinned by brain structures such as the amygdala
and medial prefrontal cortex (mPFC). In this study, we examine age-related efects on the function and structural connectivity of this system in threat extinction learning in adolescence and young adulthood. Younger age was associated with greater amygdala activity and later engagement of the mPFC to learned threat cues as compared to safety cues. Furthermore, greater structural integrity of the uncinate fasciculus, a white matter tract that connects the amygdala and mPFC, mediated the
relationship between age and mPFC engagement during extinction learning. These fndings suggest that age-related changes in the structure and function of amygdala-mPFC circuitry may underlie the
protracted maturation of threat regulatory precesses
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Dissociable roles for the striatal cholinergic system in different flexibility contexts
The production of behavioural flexibility requires the coordination and integration of information from across the brain, by the dorsal striatum. In particular, the striatal cholinergic system is thought to be important for the modulation of striatal activity. Research from animal literature has shown that chemical inactivation of the dorsal striatum leads to impairments in reversal learning. Furthermore, proton magnetic resonance spectroscopy work has shown that the striatal cholinergic system is also importaiknt for reversal learning in humans. Here, we aim to assess whether the state of the dorsal striatal cholinergic system at rest is related to serial reversal learning in humans. We provide preliminary results showing that variability in choline in the dorsal striatum is significantly related to both the number of perseverative and regressive errors that participants make, and their rate of learning from positive and negative prediction errors. These findings, in line with previous work, suggest the resting state of dorsal striatal cholinergic system has important implications for producing flexible behaviour. However, these results also suggest the system may have heterogeneous functionality across different types of tasks measuring behavioural flexibility. These findings provide a starting point for further interrogation into understanding the functional role of the striatal cholinergic system in flexibility
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Functional neurochemical imaging of the human striatal cholinergic system during reversal learning
Animal studies have shown that acetylcholine (ACh) levels in the dorsal striatum play a role in reversal learning. However, this has not been studied in humans due to a lack of appropriate non-invasive techniques. Proton magnetic resonance spectroscopy (1H-MRS) can be used to measure metabolite levels in humans in vivo. Although it cannot be used to study ACh directly, 1H-MRS can be used to study choline, an ACh precursor which is linked to activity-dependent ACh release. The aim of this study was to use functional-1H-MRS (fMRS) to measure changes in choline levels in the human dorsal striatum during performance of a probabilistic reversal learning task. We demonstrate a task-dependent decrease in choline, specifically during reversal, but not initial, learning. We interpret this to reflect a sustained increase in ACh levels, which is in line with findings from the animal literature. This task-dependent change was specific to choline and was not observed in control metabolites. These findings provide support for the use of fMRS in the in vivo study of the human cholinergic system
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Thinking about others and the future: neural correlates of perspective taking relate to preferences for delayed rewards
We infer the thoughts and feelings of others by taking their perspectives. Similar processes could be used to understand how we will be affected by future events, by allowing us to take the perspective of our future self. In this paper, we test this idea using a previously presented framework for guiding predictions. The framework proposes that a shared neural mechanism is involved in controlling egocentric bias, both while shifting our perspective away from self and towards others, and while shifting our perspective from immediate to future perspectives. To test this framework, 36 adults performed an intertemporal choice task. They were then scanned using 3T functional magnetic resonance imaging while completing a false-belief “localizer” task, which requires egocentric bias control. A positive correlation was observed between the right temporoparietal junction (rTPJ) response during the false-belief task, and preferences for delayed rewards in intertemporal choices. A subset of participants performed the intertemporal choice task again in the scanner, which revealed that the response of the same rTPJ cluster, individually localized during the false-belief task, was higher during delayed over immediate reward choices. In addition, functional connectivity between the rTPJ and ventromedial prefrontal cortex was found to differ between immediate and delayed choices. The current results indicate an overlap in processes of egocentric bias control and those that determine preferences in intertemporal choices, offering a social cognitive explanation for why rewards are devalued with delay in temporal discounting
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Regional striatal cholinergic involvement in human behavioural flexibility
Animal studies have shown that the striatal cholinergic system plays a role in behavioural flexibility but, until recently, this system could not be studied in humans due to a lack of appropriate non-invasive techniques. Using proton magnetic resonance spectroscopy (1H-MRS) we recently showed that the concentration of dorsal striatal choline (an acetylcholine precursor) changes during reversal learning (a measure of behavioural flexibility) in humans. The aim of the present study was to examine whether regional average striatal choline was associated with reversal learning. 36 participants (mean age = 24.8, range = 18-32, 20 female) performed a probabilistic learning task with a reversal component. We measured choline at rest in both the dorsal and ventral striatum using 1H-MRS. Task performance was described using a simple reinforcement learning model that dissociates the contributions of positive and negative prediction errors to learning. Average levels of choline in the dorsal striatum were associated with performance during reversal, but not during initial learning. Specifically, lower levels of choline in the dorsal striatum were associated with a lower number of perseverative trials. Moreover, choline levels explained inter-individual variance in perseveration over and above that explained by learning from negative prediction errors. These findings suggest that the dorsal striatal cholinergic system plays an important role in behavioural flexibility, in line with evidence from the animal literature and our previous work in humans. Additionally, this work provides further support for the idea of measuring choline with 1H-MRS as a non-invasive way of studying human cholinergic neurochemistr
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Systematic validation of an automated thalamic parcellation technique using anatomical data at 3T
The thalamus is a brain region formed from functionally distinct nuclei, which contribute in important ways to various cognitive processes. Yet, much of the human neuroscience literature treats the thalamus as one homogeneous region, and consequently the unique contribution of specific nuclei to behaviour remains under-appreciated. This is likely due in part to the technical challenge of dissociating nuclei using conventional structural imaging approaches. Yet, multiple algorithms exist in the neuroimaging literature for the automated segmentation of thalamic nuclei. One recent approach developed by Iglesias and colleagues (2018) generates segmentations by applying a probabilistic atlas to subject-space anatomical images using the FreeSurfer software. Here, we systematically validate the efficacy of this segmentation approach in delineating thalamic nuclei using Human Connectome Project data. We provide several metrics quantifying the quality of segmentations relative to the Morel stereotaxic atlas, a widely accepted anatomical atlas based on cyto- and myeloarchitecture. The automated segmentation approach generated boundaries between the anterior, lateral, posterior, and medial divisions of the thalamus. Segmentation efficacy, as measured by metrics of dissimilarity (Average Hausdorff Distance) and overlap (DICE coefficient) within groups was mixed. Regions were better delineated in anterior, lateral and medial thalamus than the posterior thalamus, however all the volumes for all segmented nuclei were significantly different to the corresponding region of the Morel atlas. These mixed results suggest users should exercise care when using this approach to study the structural or functional relevance of a given thalamic nucleus
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Inter-rater reliability of functional MRI data quality control assessments: a standardised protocol and practical guide using pyfMRIqc
Quality control is a critical step in the processing and analysis of functional magnetic resonance imaging data. Its purpose is to remove problematic data that could otherwise lead to downstream errors in the analysis and reporting of results. The manual inspection of data can be a laborious and error-prone process that is susceptible to human error. The development of automated tools aims to mitigate these issues. One such tool is pyfMRIqc, which we previously developed as a user-friendly method for assessing data quality. Yet, these methods still generate output that requires subjective interpretations about whether the quality of a given dataset meets an acceptable standard for further analysis. Here we present a quality control protocol using pyfMRIqc and assess the inter-rater reliability of four independent raters using this protocol for data from the fMRI Open QC project (https://osf.io/qaesm/). Data were classified by raters as either “include,” “uncertain,” or “exclude.” There was moderate to substantial agreement between raters for “include” and “exclude,” but little to no agreement for “uncertain.” In most cases only a single rater used the “uncertain” classification for a given participant’s data, with the remaining raters showing agreement for “include”/“exclude” decisions in all but one case. We suggest several approaches to increase rater agreement and reduce disagreement for “uncertain” cases, aiding classification consistency
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Disorder-specific functional abnormalities during temporal discounting in youth with Attention Deficit Hyperactivity Disorder (ADHD), Autism and comorbid ADHD and Autism
Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share cognitive abnormalities in temporal foresight. A key question is whether shared cognitive phenotypes are based on common or different underlying pathophysiologies and whether comorbid patients have additive neurofunctional deficits, resemble one of the disorders or have a different pathophysiology. We compared age- and IQ-matched boys with non-comorbid ADHD (18), non-comorbid ASD (15), comorbid ADHD and ASD (13) and healthy controls (18) using functional magnetic resonance imaging (fMRI) during a temporal discounting task. Only the ASD and the comorbid groups discounted delayed rewards more steeply. The fMRI data showed both shared and disorder-specific abnormalities in the three groups relative to controls in their brain-behaviour associations. The comorbid group showed both unique and more severe brain-discounting associations than controls and the non-comorbid patient groups in temporal discounting areas of ventromedial and lateral prefrontal cortex, ventral striatum and anterior cingulate, suggesting that comorbidity is neither an endophenocopy of the two pure disorders nor an additive pathology
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Disorder-specific and shared brain abnormalities during vigilance in autism and obsessive-compulsive disorder
Background
Autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) are often comorbid and share similarities across some cognitive phenotypes, including certain aspects of attention. However, no functional magnetic resonance imaging (fMRI) studies have compared the underlying neural mechanisms contributing to these shared phenotypes.
Methods
Age and IQ-matched boys between 11 and 17 years old with ASD (N=20), OCD (N=20) and healthy controls (N = 20) performed a parametrically modulated psychomotor vigilance fMRI task. Brain activation and performance were compared between adolescents with OCD, ASD and controls.
Results
While boys with ASD and OCD were not impaired on task performance, there was a significant group by attention load interaction in several brain regions. With increasing attention load, left inferior frontal cortex/insula as well as left inferior parietal lobe/pre/post-central gyrus were progressively less activated in OCD boys relative to the other two groups. In addition, OCD boys showed progressively increased activation with increasing attention load in rostromedial prefrontal/anterior cingulate cortex relative to ASD and control boys. Shared neurofunctional abnormalities between ASD and OCD boys included increased activation with increasing attention load in cerebellum and occipital regions, possibly reflecting increased default mode network activation.
Conclusions
This first fMRI study to compare boys with ASD and OCD showed shared abnormalities in posterior cerebellar-occipital brain regions. However, OCD boys showed a disorder-specific pattern of reduced activation in left inferior frontal and temporo-parietal regions but increased activation of medial frontal regions which may potentially be related to neurobiological mechanisms underlying cognitive and clinical phenotypes of OCD
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Nothing is safe: intolerance of uncertainty is associated with compromised fear extinction learning
Extinction-resistant fear is considered to be a central feature of pathological anxiety. Here we sought to determine if individual differences in Intolerance of Uncertainty (IU), a potential risk factor for anxiety disorders, underlies compromised fear extinction. We tested this hypothesis by recording electrodermal activity in 38 healthy participants during fear acquisition and extinction. We assessed the temporality of fear extinction, by examining early and late extinction learning. During early extinction, low IU was associated with larger skin conductance responses to learned threat vs. safety cues, whereas high IU was associated with skin conductance responding to both threat and safety cues, but no cue discrimination. During late extinction, low IU showed no difference in skin conductance between learned threat and safety cues, whilst high IU predicted continued fear expression to learned threat, indexed by larger skin conductance to threat vs. safety cues. These findings suggest a critical role of uncertainty-based mechanisms in the maintenance of learned fear
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