Anastasia Christakou | University of Reading (original) (raw)

Papers by Anastasia Christakou

Research paper thumbnail of Inter-rater reliability of functional MRI data quality control assessments: A standardised protocol and practical guide using pyfMRIqc

Frontiers in Neuroscience

Quality control is a critical step in the processing and analysis of functional magnetic resonanc... more 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.” Th...

Research paper thumbnail of Orbitofrontal and Thalamic Influences on Striatal Involvement in Human Reversal Learning

ABSTRACTCognitive flexibility is crucial for adaptation and is disrupted in neuropsychiatric diso... more ABSTRACTCognitive flexibility is crucial for adaptation and is disrupted in neuropsychiatric disorders and psychopathology. Human studies of flexibility using reversal learning tasks typically contrast error trials before and after reversal, which provides little information about the mechanisms that support learning and expressing a new response. However, animal studies suggest a specific role in this latter process for the connections between the dorsal striatum and the centromedian parafascicular (CM-Pf) thalamus, a system which may recruit the striatal cholinergic interneurons, but which is not well understood in humans. This study investigated the role of this system in human probabilistic reversal learning, specifically with respect to learning a new response strategy, contrasting its function to that of the better understood orbitoftontal-striatal systems. Using psychophysiological interaction (PPI) analysis of functional magnetic resonance imaging (fMRI) data we show that co...

Research paper thumbnail of Regional Striatal Cholinergic Involvement in Human Behavioral Flexibility

The Journal of Neuroscience, 2019

Animal studies have shown that the striatal cholinergic system plays a role in behavioral flexibi... more Animal studies have shown that the striatal cholinergic system plays a role in behavioral flexibility but, until recently, this system could not be studied in humans due to a lack of appropriate noninvasive techniques. Using proton magnetic resonance spectroscopy, we recently showed that the concentration of dorsal striatal choline (an acetylcholine precursor) changes during reversal learning (a measure of behavioral flexibility) in humans. The aim of the present study was to examine whether regional average striatal choline was associated with reversal learning. A total of 22 participants (mean age ϭ 25.2 years, range ϭ 18-32 years, 13 female) reached learning criterion in a probabilistic learning task with a reversal component. We measured choline at rest in both the dorsal and ventral striatum using magnetic resonance spectroscopy. 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 interindividual 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 behavioral 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 magnetic resonance spectroscopy as a noninvasive way of studying human cholinergic neurochemistry.

Research paper thumbnail of Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood

Scientific Reports, 2019

Previous research in rodents and humans points to an evolutionarily conserved profile of blunted ... more Previous research in rodents and humans points to an evolutionarily conserved profile 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 effects 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 findings suggest that age-related changes in the structure and function of amygdala-mPFC circuitry may underlie the protracted maturation of threat regulatory processes.

Research paper thumbnail of Thinking about others and the future: Neural correlates of perspective taking relate to preferences for delayed rewards

Cognitive, Affective, & Behavioral Neuroscience, 2017

We infer the thoughts and feelings of others by taking their perspectives. Similar processes coul... more 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 Blocalizer^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.

Research paper thumbnail of A kinematic examination of dual-route processing for action imitation

Attention, Perception, & Psychophysics, 2018

The dual-route model of imitation suggests that meaningful and meaningless actions are processed ... more The dual-route model of imitation suggests that meaningful and meaningless actions are processed through either an indirect or a direct route, respectively. Evidence indicates that the direct route is more cognitively demanding since it relies on mapping visuospatial properties of the observed action on to a performed one. These cognitive demands might negatively influence reaction time and accuracy for actions performed following a meaningless action under time constraints. However, how meaningful and meaningless action imitation processing is reflected in movement kinematics is not yet clear. We wanted to confirm whether meaningless action performance incurs a reaction time cost, whether the cost is reflected in kinematics, and, more generally, to examine kinematic markers of emblematic meaningful and meaningless action imitation. We examined participants' reaction time and wrist movements when they imitated emblematic meaningful or matched meaningless gestures in either blocks of the same action type or mixed blocks. Meaningless actions were associated with a greater correction period at the end of the movement, possibly reflecting a strategy designed to ensure accurate completion for less familiar actions under time constraints. Furthermore, in mixed blocks, trials following meaningless actions had a significantly increased reaction time, supporting previous claims that route selection for action imitation may be stimulus-driven. However, there was only convincing evidence for this effect with an interval of~2,948ms, but not~3,573ms or~2,553ms, between movements. Future work motion-tracking the entire hand to assess imitation accuracy, and more closely examining the influence of duration between movements, may help to explain these effects.

Research paper thumbnail of Functional neurochemical imaging of the human striatal cholinergic system during reversal learning

The European journal of neuroscience, Jan 19, 2017

Animal studies have shown that acetylcholine (ACh) levels in the dorsal striatum play a role in r... more 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 (H-MRS) can be used to measure metabolite levels in humans in vivo. Although it cannot be used to study ACh directly,H-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-H-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 f...

Research paper thumbnail of In vivo functional neurochemistry of human cortical cholinergic function during visuospatial attention

PloS one, 2017

Cortical acetylcholine is involved in key cognitive processes such as visuospatial attention. Dys... more Cortical acetylcholine is involved in key cognitive processes such as visuospatial attention. Dysfunction in the cholinergic system has been described in a number of neuropsychiatric disorders. Levels of brain acetylcholine can be pharmacologically manipulated, but it is not possible to directly measure it in vivo in humans. However, key parts of its biochemical cascade in neural tissue, such as choline, can be measured using magnetic resonance spectroscopy (MRS). There is evidence that levels of choline may be an indirect but proportional measure of acetylcholine availability in brain tissue. In this study, we measured relative choline levels in the parietal cortex using functional (event-related) MRS (fMRS) during performance of a visuospatial attention task, with a modelling approach verified using simulated data. We describe a task-driven interaction effect on choline concentration, specifically driven by contralateral attention shifts. Our results suggest that choline MRS has t...

Research paper thumbnail of Nothing is safe: Intolerance of uncertainty is associated with compromised fear extinction learning

Biological Psychology, 2016

Extinction-resistant fear is considered to be a central feature of pathological anxiety. Here we ... more 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.

Research paper thumbnail of Four-legged snake fossil sparks legal investigation

Nature, 2015

Brazilian authorities are looking into whether the specimen was exported illegally.

Research paper thumbnail of Four-legged fossil snake is a world first

Nature, 2015

Four-legged fossil snake is a world first 'Hugging' creature from Brazil shakes up picture of sna... more Four-legged fossil snake is a world first 'Hugging' creature from Brazil shakes up picture of snake evolution.

Research paper thumbnail of Intolerance of uncertainty predicts fear extinction in amygdala-ventromedial prefrontal cortical circuitry

Biology of Mood & Anxiety Disorders, 2015

Background: Coordination of activity between the amygdala and ventromedial prefrontal cortex (vmP... more Background: Coordination of activity between the amygdala and ventromedial prefrontal cortex (vmPFC) is important for fear-extinction learning. Aberrant recruitment of this circuitry is associated with anxiety disorders. Here, we sought to determine if individual differences in future threat uncertainty sensitivity, a potential risk factor for anxiety disorders, underly compromised recruitment of fear extinction circuitry. Twenty-two healthy subjects completed a cued fear conditioning task with acquisition and extinction phases. During the task, pupil dilation, skin conductance response, and functional magnetic resonance imaging were acquired. We assessed the temporality of fear extinction learning by splitting the extinction phase into early and late extinction. Threat uncertainty sensitivity was measured using self-reported intolerance of uncertainty (IU). Results: During early extinction learning, we found low IU scores to be associated with larger skin conductance responses and right amygdala activity to learned threat vs. safety cues, whereas high IU scores were associated with no skin conductance discrimination and greater activity within the right amygdala to previously learned safety cues. In late extinction learning, low IU scores were associated with successful inhibition of previously learned threat, reflected in comparable skin conductance response and right amgydala activity to learned threat vs. safety cues, whilst high IU scores were associated with continued fear expression to learned threat, indexed by larger skin conductance and amygdala activity to threat vs. safety cues. In addition, high IU scores were associated with greater vmPFC activity to threat vs. safety cues in late extinction. Similar patterns of IU and extinction learning were found for pupil dilation. The results were specific for IU and did not generalize to self-reported trait anxiety. Conclusions: Overall, the neural and psychophysiological patterns observed here suggest high IU individuals to disproportionately generalize threat during times of uncertainty, which subsequently compromises fear extinction learning. More broadly, these findings highlight the potential of intolerance of uncertainty-based mechanisms to help understand pathological fear in anxiety disorders and inform potential treatment targets.

Research paper thumbnail of The role of simulation in intertemporal choices

Frontiers in neuroscience, 2015

One route to understanding the thoughts and feelings of others is by mentally putting one's s... more One route to understanding the thoughts and feelings of others is by mentally putting one's self in their shoes and seeing the world from their perspective, i.e., by simulation. Simulation is potentially used not only for inferring how others feel, but also for predicting how we ourselves will feel in the future. For instance, one might judge the worth of a future reward by simulating how much it will eventually be enjoyed. In intertemporal choices between smaller immediate and larger delayed rewards, it is observed that as the length of delay increases, delayed rewards lose subjective value; a phenomenon known as temporal discounting. In this article, we develop a theoretical framework for the proposition that simulation mechanisms involved in empathizing with others also underlie intertemporal choices. This framework yields a testable psychological account of temporal discounting based on simulation. Such an account, if experimentally validated, could have important implicatio...

Research paper thumbnail of Present simple and continuous: Emergence of self-regulation and contextual sophistication in adolescent decision-making

Sophisticated, intentional decision-making is a hallmark of mature, self-aware behaviour. Althoug... more Sophisticated, intentional decision-making is a hallmark of mature, self-aware behaviour. Although neural, psychological, interpersonal, and socioeconomic elements that contribute to such adaptive, foresighted behaviour mature and/or change throughout the lifespan , here we concentrate on relevant maturational processes that take place during adolescence, a period of disproportionate developmental opportunity and risk. A brief, eclectic overview is presented of recent evidence, new challenges, and current thinking on the fundamental mechanisms that mature throughout adolescence to support adaptive, self-controlled decision-making. This is followed by a proposal for the putative contribution of frontostriatal mechanisms to the moment-to-moment assembly of evaluative heuristics that mediate increased decision-making sophistication, promoting the maturation of self-regulated behaviour through adolescence and young adulthood.

Research paper thumbnail of The role of empathy in choosing rewards from another's perspective

Frontiers in Human Neuroscience, 2013

Research paper thumbnail of Intolerance of uncertainty predicts fear extinction in amygdala-ventromedial prefrontal cortical circuitry

Background Coordination of activity between the amygdala and ventromedial prefrontal cortex (vmP... more Background
Coordination of activity between the amygdala and ventromedial prefrontal cortex (vmPFC) is important for fear-extinction learning. Aberrant recruitment of this circuitry is associated with anxiety disorders. Here, we sought to determine if individual differences in future threat uncertainty sensitivity, a potential risk factor for anxiety disorders, underly compromised recruitment of fear extinction circuitry.

Twenty-two healthy subjects completed a cued fear conditioning task with acquisition and extinction phases. During the task, pupil dilation, skin conductance response, and functional magnetic resonance imaging were acquired. We assessed the temporality of fear extinction learning by splitting the extinction phase into early and late extinction. Threat uncertainty sensitivity was measured using self-reported intolerance of uncertainty (IU).

Results
During early extinction learning, we found low IU scores to be associated with larger skin conductance responses and right amygdala activity to learned threat vs. safety cues, whereas high IU scores were associated with no skin conductance discrimination and greater activity within the right amygdala to previously learned safety cues. In late extinction learning, low IU scores were associated with successful inhibition of previously learned threat, reflected in comparable skin conductance response and right amgydala activity to learned threat vs. safety cues, whilst high IU scores were associated with continued fear expression to learned threat, indexed by larger skin conductance and amygdala activity to threat vs. safety cues. In addition, high IU scores were associated with greater vmPFC activity to threat vs. safety cues in late extinction. Similar patterns of IU and extinction learning were found for pupil dilation. The results were specific for IU and did not generalize to self-reported trait anxiety.

Conclusions
Overall, the neural and psychophysiological patterns observed here suggest high IU individuals to disproportionately generalize threat during times of uncertainty, which subsequently compromises fear extinction learning. More broadly, these findings highlight the potential of intolerance of uncertainty-based mechanisms to help understand pathological fear in anxiety disorders and inform potential treatment targets.

Research paper thumbnail of The role of simulation in intertemporal choices

One route to understanding the thoughts and feelings of others is by mentally putting one’s self ... more One route to understanding the thoughts and feelings of others is by mentally putting one’s self in their shoes and seeing the world from their perspective, called simulation. Simulation is potentially used not only for inferring how others feel, but also for predicting how we ourselves will feel in the future. For instance, one might judge the worth of a future reward by simulating how much it will eventually be enjoyed. In intertemporal choices between smaller immediate and larger delayed rewards, it is observed that as the length of delay increases, delayed larger rewards lose subjective value; a phenomenon known as temporal discounting. In this article, we develop a theoretical framework for the proposition that simulation mechanisms involved in empathising with others also underlie intertemporal choices. This framework yields a testable psychological account of temporal discounting based on simulation. Such an account, if experimentally validated, could have important implications for how simulation mechanisms are investigated, and makes predictions about special populations characterised by putative deficits in simulating others.

Research paper thumbnail of Present simple and continuous: Emergence of self-regulation and contextual sophistication in adolescent decision-making

Sophisticated, intentional decision-making is a hallmark of mature, self-aware behaviour. Althoug... more Sophisticated, intentional decision-making is a hallmark of mature, self-aware behaviour. Although neural, psychological, interpersonal, and socioeconomic elements that contribute to such adaptive, foresighted behaviour mature and/or change throughout the life-span, here we concentrate on relevant maturational processes that take place during adolescence, a period of disproportionate developmental opportunity and risk. A brief, eclectic overview is presented of recent evidence, new challenges, and current thinking on the fundamental mechanisms that mature throughout adolescence to support adaptive, self-controlled decision-making. This is followed by a proposal for the putative contribution of frontostriatal mechanisms to the moment-to-moment assembly of evaluative heuristics that mediate increased decision-making sophistication, promoting the maturation of self-regulated behaviour through adolescence and young adulthood.

Research paper thumbnail of Abnormal Functional Activation and Maturation of Fronto-Striato-Temporal and Cerebellar Regions During Sustained Attention in Autism Spectrum Disorder

Objective Sustained attention problems are common in people with autism spectrum disorder (ASD) ... more Objective Sustained attention problems are common in people with autism spectrum disorder (ASD) and may have significant implications for the diagnosis and management of ASD and associated comorbidities. Furthermore, ASD has been associated with atypical structural brain development. The authors used functional MRI to investigate the functional brain maturation of attention between childhood and adulthood in people with ASD.

Method Using a parametrically modulated sustained attention/vigilance task, the authors examined brain activation and its linear correlation with age between childhood and adulthood in 46 healthy male adolescents and adults (ages 11–35 years) with ASD and 44 age- and IQ-matched typically developing comparison subjects.

Results Relative to the comparison group, the ASD group had significantly poorer task performance and significantly lower activation in inferior prefrontal cortical, medial prefrontal cortical, striato-thalamic, and lateral cerebellar regions. A conjunction analysis of this analysis with group differences in brain-age correlations showed that the comparison group, but not the ASD group, had significantly progressively increased activation with age in these regions between childhood and adulthood, suggesting abnormal functional brain maturation in ASD. Several regions that showed both abnormal activation and functional maturation were associated with poorer task performance and clinical measures of ASD and inattention.

Conclusions The results provide first evidence that abnormalities in sustained attention networks in individuals with ASD are associated with underlying abnormalities in the functional brain maturation of these networks between late childhood and adulthood.

Research paper thumbnail of 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 como... more 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.

Research paper thumbnail of Inter-rater reliability of functional MRI data quality control assessments: A standardised protocol and practical guide using pyfMRIqc

Frontiers in Neuroscience

Quality control is a critical step in the processing and analysis of functional magnetic resonanc... more 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.” Th...

Research paper thumbnail of Orbitofrontal and Thalamic Influences on Striatal Involvement in Human Reversal Learning

ABSTRACTCognitive flexibility is crucial for adaptation and is disrupted in neuropsychiatric diso... more ABSTRACTCognitive flexibility is crucial for adaptation and is disrupted in neuropsychiatric disorders and psychopathology. Human studies of flexibility using reversal learning tasks typically contrast error trials before and after reversal, which provides little information about the mechanisms that support learning and expressing a new response. However, animal studies suggest a specific role in this latter process for the connections between the dorsal striatum and the centromedian parafascicular (CM-Pf) thalamus, a system which may recruit the striatal cholinergic interneurons, but which is not well understood in humans. This study investigated the role of this system in human probabilistic reversal learning, specifically with respect to learning a new response strategy, contrasting its function to that of the better understood orbitoftontal-striatal systems. Using psychophysiological interaction (PPI) analysis of functional magnetic resonance imaging (fMRI) data we show that co...

Research paper thumbnail of Regional Striatal Cholinergic Involvement in Human Behavioral Flexibility

The Journal of Neuroscience, 2019

Animal studies have shown that the striatal cholinergic system plays a role in behavioral flexibi... more Animal studies have shown that the striatal cholinergic system plays a role in behavioral flexibility but, until recently, this system could not be studied in humans due to a lack of appropriate noninvasive techniques. Using proton magnetic resonance spectroscopy, we recently showed that the concentration of dorsal striatal choline (an acetylcholine precursor) changes during reversal learning (a measure of behavioral flexibility) in humans. The aim of the present study was to examine whether regional average striatal choline was associated with reversal learning. A total of 22 participants (mean age ϭ 25.2 years, range ϭ 18-32 years, 13 female) reached learning criterion in a probabilistic learning task with a reversal component. We measured choline at rest in both the dorsal and ventral striatum using magnetic resonance spectroscopy. 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 interindividual 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 behavioral 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 magnetic resonance spectroscopy as a noninvasive way of studying human cholinergic neurochemistry.

Research paper thumbnail of Multimodal evidence for delayed threat extinction learning in adolescence and young adulthood

Scientific Reports, 2019

Previous research in rodents and humans points to an evolutionarily conserved profile of blunted ... more Previous research in rodents and humans points to an evolutionarily conserved profile 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 effects 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 findings suggest that age-related changes in the structure and function of amygdala-mPFC circuitry may underlie the protracted maturation of threat regulatory processes.

Research paper thumbnail of Thinking about others and the future: Neural correlates of perspective taking relate to preferences for delayed rewards

Cognitive, Affective, & Behavioral Neuroscience, 2017

We infer the thoughts and feelings of others by taking their perspectives. Similar processes coul... more 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 Blocalizer^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.

Research paper thumbnail of A kinematic examination of dual-route processing for action imitation

Attention, Perception, & Psychophysics, 2018

The dual-route model of imitation suggests that meaningful and meaningless actions are processed ... more The dual-route model of imitation suggests that meaningful and meaningless actions are processed through either an indirect or a direct route, respectively. Evidence indicates that the direct route is more cognitively demanding since it relies on mapping visuospatial properties of the observed action on to a performed one. These cognitive demands might negatively influence reaction time and accuracy for actions performed following a meaningless action under time constraints. However, how meaningful and meaningless action imitation processing is reflected in movement kinematics is not yet clear. We wanted to confirm whether meaningless action performance incurs a reaction time cost, whether the cost is reflected in kinematics, and, more generally, to examine kinematic markers of emblematic meaningful and meaningless action imitation. We examined participants' reaction time and wrist movements when they imitated emblematic meaningful or matched meaningless gestures in either blocks of the same action type or mixed blocks. Meaningless actions were associated with a greater correction period at the end of the movement, possibly reflecting a strategy designed to ensure accurate completion for less familiar actions under time constraints. Furthermore, in mixed blocks, trials following meaningless actions had a significantly increased reaction time, supporting previous claims that route selection for action imitation may be stimulus-driven. However, there was only convincing evidence for this effect with an interval of~2,948ms, but not~3,573ms or~2,553ms, between movements. Future work motion-tracking the entire hand to assess imitation accuracy, and more closely examining the influence of duration between movements, may help to explain these effects.

Research paper thumbnail of Functional neurochemical imaging of the human striatal cholinergic system during reversal learning

The European journal of neuroscience, Jan 19, 2017

Animal studies have shown that acetylcholine (ACh) levels in the dorsal striatum play a role in r... more 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 (H-MRS) can be used to measure metabolite levels in humans in vivo. Although it cannot be used to study ACh directly,H-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-H-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 f...

Research paper thumbnail of In vivo functional neurochemistry of human cortical cholinergic function during visuospatial attention

PloS one, 2017

Cortical acetylcholine is involved in key cognitive processes such as visuospatial attention. Dys... more Cortical acetylcholine is involved in key cognitive processes such as visuospatial attention. Dysfunction in the cholinergic system has been described in a number of neuropsychiatric disorders. Levels of brain acetylcholine can be pharmacologically manipulated, but it is not possible to directly measure it in vivo in humans. However, key parts of its biochemical cascade in neural tissue, such as choline, can be measured using magnetic resonance spectroscopy (MRS). There is evidence that levels of choline may be an indirect but proportional measure of acetylcholine availability in brain tissue. In this study, we measured relative choline levels in the parietal cortex using functional (event-related) MRS (fMRS) during performance of a visuospatial attention task, with a modelling approach verified using simulated data. We describe a task-driven interaction effect on choline concentration, specifically driven by contralateral attention shifts. Our results suggest that choline MRS has t...

Research paper thumbnail of Nothing is safe: Intolerance of uncertainty is associated with compromised fear extinction learning

Biological Psychology, 2016

Extinction-resistant fear is considered to be a central feature of pathological anxiety. Here we ... more 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.

Research paper thumbnail of Four-legged snake fossil sparks legal investigation

Nature, 2015

Brazilian authorities are looking into whether the specimen was exported illegally.

Research paper thumbnail of Four-legged fossil snake is a world first

Nature, 2015

Four-legged fossil snake is a world first 'Hugging' creature from Brazil shakes up picture of sna... more Four-legged fossil snake is a world first 'Hugging' creature from Brazil shakes up picture of snake evolution.

Research paper thumbnail of Intolerance of uncertainty predicts fear extinction in amygdala-ventromedial prefrontal cortical circuitry

Biology of Mood & Anxiety Disorders, 2015

Background: Coordination of activity between the amygdala and ventromedial prefrontal cortex (vmP... more Background: Coordination of activity between the amygdala and ventromedial prefrontal cortex (vmPFC) is important for fear-extinction learning. Aberrant recruitment of this circuitry is associated with anxiety disorders. Here, we sought to determine if individual differences in future threat uncertainty sensitivity, a potential risk factor for anxiety disorders, underly compromised recruitment of fear extinction circuitry. Twenty-two healthy subjects completed a cued fear conditioning task with acquisition and extinction phases. During the task, pupil dilation, skin conductance response, and functional magnetic resonance imaging were acquired. We assessed the temporality of fear extinction learning by splitting the extinction phase into early and late extinction. Threat uncertainty sensitivity was measured using self-reported intolerance of uncertainty (IU). Results: During early extinction learning, we found low IU scores to be associated with larger skin conductance responses and right amygdala activity to learned threat vs. safety cues, whereas high IU scores were associated with no skin conductance discrimination and greater activity within the right amygdala to previously learned safety cues. In late extinction learning, low IU scores were associated with successful inhibition of previously learned threat, reflected in comparable skin conductance response and right amgydala activity to learned threat vs. safety cues, whilst high IU scores were associated with continued fear expression to learned threat, indexed by larger skin conductance and amygdala activity to threat vs. safety cues. In addition, high IU scores were associated with greater vmPFC activity to threat vs. safety cues in late extinction. Similar patterns of IU and extinction learning were found for pupil dilation. The results were specific for IU and did not generalize to self-reported trait anxiety. Conclusions: Overall, the neural and psychophysiological patterns observed here suggest high IU individuals to disproportionately generalize threat during times of uncertainty, which subsequently compromises fear extinction learning. More broadly, these findings highlight the potential of intolerance of uncertainty-based mechanisms to help understand pathological fear in anxiety disorders and inform potential treatment targets.

Research paper thumbnail of The role of simulation in intertemporal choices

Frontiers in neuroscience, 2015

One route to understanding the thoughts and feelings of others is by mentally putting one's s... more One route to understanding the thoughts and feelings of others is by mentally putting one's self in their shoes and seeing the world from their perspective, i.e., by simulation. Simulation is potentially used not only for inferring how others feel, but also for predicting how we ourselves will feel in the future. For instance, one might judge the worth of a future reward by simulating how much it will eventually be enjoyed. In intertemporal choices between smaller immediate and larger delayed rewards, it is observed that as the length of delay increases, delayed rewards lose subjective value; a phenomenon known as temporal discounting. In this article, we develop a theoretical framework for the proposition that simulation mechanisms involved in empathizing with others also underlie intertemporal choices. This framework yields a testable psychological account of temporal discounting based on simulation. Such an account, if experimentally validated, could have important implicatio...

Research paper thumbnail of Present simple and continuous: Emergence of self-regulation and contextual sophistication in adolescent decision-making

Sophisticated, intentional decision-making is a hallmark of mature, self-aware behaviour. Althoug... more Sophisticated, intentional decision-making is a hallmark of mature, self-aware behaviour. Although neural, psychological, interpersonal, and socioeconomic elements that contribute to such adaptive, foresighted behaviour mature and/or change throughout the lifespan , here we concentrate on relevant maturational processes that take place during adolescence, a period of disproportionate developmental opportunity and risk. A brief, eclectic overview is presented of recent evidence, new challenges, and current thinking on the fundamental mechanisms that mature throughout adolescence to support adaptive, self-controlled decision-making. This is followed by a proposal for the putative contribution of frontostriatal mechanisms to the moment-to-moment assembly of evaluative heuristics that mediate increased decision-making sophistication, promoting the maturation of self-regulated behaviour through adolescence and young adulthood.

Research paper thumbnail of The role of empathy in choosing rewards from another's perspective

Frontiers in Human Neuroscience, 2013

Research paper thumbnail of Intolerance of uncertainty predicts fear extinction in amygdala-ventromedial prefrontal cortical circuitry

Background Coordination of activity between the amygdala and ventromedial prefrontal cortex (vmP... more Background
Coordination of activity between the amygdala and ventromedial prefrontal cortex (vmPFC) is important for fear-extinction learning. Aberrant recruitment of this circuitry is associated with anxiety disorders. Here, we sought to determine if individual differences in future threat uncertainty sensitivity, a potential risk factor for anxiety disorders, underly compromised recruitment of fear extinction circuitry.

Twenty-two healthy subjects completed a cued fear conditioning task with acquisition and extinction phases. During the task, pupil dilation, skin conductance response, and functional magnetic resonance imaging were acquired. We assessed the temporality of fear extinction learning by splitting the extinction phase into early and late extinction. Threat uncertainty sensitivity was measured using self-reported intolerance of uncertainty (IU).

Results
During early extinction learning, we found low IU scores to be associated with larger skin conductance responses and right amygdala activity to learned threat vs. safety cues, whereas high IU scores were associated with no skin conductance discrimination and greater activity within the right amygdala to previously learned safety cues. In late extinction learning, low IU scores were associated with successful inhibition of previously learned threat, reflected in comparable skin conductance response and right amgydala activity to learned threat vs. safety cues, whilst high IU scores were associated with continued fear expression to learned threat, indexed by larger skin conductance and amygdala activity to threat vs. safety cues. In addition, high IU scores were associated with greater vmPFC activity to threat vs. safety cues in late extinction. Similar patterns of IU and extinction learning were found for pupil dilation. The results were specific for IU and did not generalize to self-reported trait anxiety.

Conclusions
Overall, the neural and psychophysiological patterns observed here suggest high IU individuals to disproportionately generalize threat during times of uncertainty, which subsequently compromises fear extinction learning. More broadly, these findings highlight the potential of intolerance of uncertainty-based mechanisms to help understand pathological fear in anxiety disorders and inform potential treatment targets.

Research paper thumbnail of The role of simulation in intertemporal choices

One route to understanding the thoughts and feelings of others is by mentally putting one’s self ... more One route to understanding the thoughts and feelings of others is by mentally putting one’s self in their shoes and seeing the world from their perspective, called simulation. Simulation is potentially used not only for inferring how others feel, but also for predicting how we ourselves will feel in the future. For instance, one might judge the worth of a future reward by simulating how much it will eventually be enjoyed. In intertemporal choices between smaller immediate and larger delayed rewards, it is observed that as the length of delay increases, delayed larger rewards lose subjective value; a phenomenon known as temporal discounting. In this article, we develop a theoretical framework for the proposition that simulation mechanisms involved in empathising with others also underlie intertemporal choices. This framework yields a testable psychological account of temporal discounting based on simulation. Such an account, if experimentally validated, could have important implications for how simulation mechanisms are investigated, and makes predictions about special populations characterised by putative deficits in simulating others.

Research paper thumbnail of Present simple and continuous: Emergence of self-regulation and contextual sophistication in adolescent decision-making

Sophisticated, intentional decision-making is a hallmark of mature, self-aware behaviour. Althoug... more Sophisticated, intentional decision-making is a hallmark of mature, self-aware behaviour. Although neural, psychological, interpersonal, and socioeconomic elements that contribute to such adaptive, foresighted behaviour mature and/or change throughout the life-span, here we concentrate on relevant maturational processes that take place during adolescence, a period of disproportionate developmental opportunity and risk. A brief, eclectic overview is presented of recent evidence, new challenges, and current thinking on the fundamental mechanisms that mature throughout adolescence to support adaptive, self-controlled decision-making. This is followed by a proposal for the putative contribution of frontostriatal mechanisms to the moment-to-moment assembly of evaluative heuristics that mediate increased decision-making sophistication, promoting the maturation of self-regulated behaviour through adolescence and young adulthood.

Research paper thumbnail of Abnormal Functional Activation and Maturation of Fronto-Striato-Temporal and Cerebellar Regions During Sustained Attention in Autism Spectrum Disorder

Objective Sustained attention problems are common in people with autism spectrum disorder (ASD) ... more Objective Sustained attention problems are common in people with autism spectrum disorder (ASD) and may have significant implications for the diagnosis and management of ASD and associated comorbidities. Furthermore, ASD has been associated with atypical structural brain development. The authors used functional MRI to investigate the functional brain maturation of attention between childhood and adulthood in people with ASD.

Method Using a parametrically modulated sustained attention/vigilance task, the authors examined brain activation and its linear correlation with age between childhood and adulthood in 46 healthy male adolescents and adults (ages 11–35 years) with ASD and 44 age- and IQ-matched typically developing comparison subjects.

Results Relative to the comparison group, the ASD group had significantly poorer task performance and significantly lower activation in inferior prefrontal cortical, medial prefrontal cortical, striato-thalamic, and lateral cerebellar regions. A conjunction analysis of this analysis with group differences in brain-age correlations showed that the comparison group, but not the ASD group, had significantly progressively increased activation with age in these regions between childhood and adulthood, suggesting abnormal functional brain maturation in ASD. Several regions that showed both abnormal activation and functional maturation were associated with poorer task performance and clinical measures of ASD and inattention.

Conclusions The results provide first evidence that abnormalities in sustained attention networks in individuals with ASD are associated with underlying abnormalities in the functional brain maturation of these networks between late childhood and adulthood.

Research paper thumbnail of 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 como... more 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.