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Research paper thumbnail of Corrigendum: Dopamine restores reward prediction errors in old age

Nature Neuroscience, 2014

Research paper thumbnail of Editorial Board

Research paper thumbnail of Confirmation of functional zones within the human subthalamic nucleus: Patterns of connectivity and sub-parcellation using diffusion weighted imaging

Neuroimage, 2012

The subthalamic nucleus (STN) is a small, glutamatergic nucleus situated in the diencephalon. A c... more The subthalamic nucleus (STN) is a small, glutamatergic nucleus situated in the diencephalon. A critical component of normal motor function, it has become a key target for deep brain stimulation in the treatment of Parkinson's disease. Animal studies have demonstrated the existence of three functional sub-zones but these have never been shown conclusively in humans. In this work, a data driven method with diffusion weighted imaging demonstrated that three distinct clusters exist within the human STN based on brain connectivity profiles. The STN was successfully sub-parcellated into these regions, demonstrating good correspondence with that described in the animal literature. The local connectivity of each sub-region supported the hypothesis of bilateral limbic, associative and motor regions occupying the anterior, mid and posterior portions of the nucleus respectively. This study is the first to achieve in-vivo, non-invasive anatomical parcellation of the human STN into three anatomical zones within normal diagnostic scan times, which has important future implications for deep brain stimulation surgery.

Research paper thumbnail of Multiparametric brainstem segmentation using a modified multivariate mixture of Gaussians

NeuroImage: Clinical, 2013

Brainstem Segmentation Modified multivariate mixture of Gaussians Voxel based morphometry Asymmetry

Research paper thumbnail of Characterizing aging in the human brainstem using quantitative multimodal MRI analysis

Frontiers in human neuroscience, 2013

Aging is ubiquitous to the human condition. The MRI correlates of healthy aging have been extensi... more Aging is ubiquitous to the human condition. The MRI correlates of healthy aging have been extensively investigated using a range of modalities, including volumetric MRI, quantitative MRI (qMRI), and diffusion tensor imaging. Despite this, the reported brainstem related changes remain sparse. This is, in part, due to the technical and methodological limitations in quantitatively assessing and statistically analyzing this region. By utilizing a new method of brainstem segmentation, a large cohort of 100 healthy adults were assessed in this study for the effects of aging within the human brainstem in vivo. Using qMRI, tensor-based morphometry (TBM), and voxel-based quantification (VBQ), the volumetric and quantitative changes across healthy adults between 19 and 75 years were characterized. In addition to the increased R2* in substantia nigra corresponding to increasing iron deposition with age, several novel findings were reported in the current study. These include selective volumetr...

Research paper thumbnail of Strategic lacunes and their relationship to cognitive impairment in cerebral small vessel disease

NeuroImage. Clinical, 2014

Lacunes are an important disease feature of cerebral small vessel disease (SVD) but their relatio... more Lacunes are an important disease feature of cerebral small vessel disease (SVD) but their relationship to cognitive impairment is not fully understood. To investigate this we determined (1) the relationship between lacune count and total lacune volume with cognition, (2) the spatial distribution of lacunes and the cognitive impact of lacune location, and (3) the whole brain anatomical covariance associated with these strategically located regions of lacune damage. One hundred and twenty one patients with symptomatic lacunar stroke and radiological leukoaraiosis were recruited and multimodal MRI and neuropsychological data acquired. Lacunes were mapped semi-automatically and their volume calculated. Lacune location was automatically determined by projection onto atlases, including an atlas which segments the thalamus based on its connectivity to the cortex. Lacune locations were correlated with neuropsychological results. Voxel based morphometry was used to create anatomical covarian...

Research paper thumbnail of Dopamine restores reward prediction errors in old age

Nature Neuroscience, 2013

Senescence affects the ability to utilize information about the likelihood of rewards for optimal... more Senescence affects the ability to utilize information about the likelihood of rewards for optimal decision-making. Using functional magnetic resonance imaging in humans, we found that healthy older adults had an abnormal signature of expected value, resulting in an incomplete reward prediction error (RPE) signal in the nucleus accumbens, a brain region that receives rich input projections from substantia nigra/ventral tegmental area (SN/VTA) dopaminergic neurons. Structural connectivity between SN/VTA and striatum, measured by diffusion tensor imaging, was tightly coupled to inter-individual differences in the expression of this expected reward value signal. The dopamine precursor levodopa (L-DOPA) increased the task-based learning rate and task performance in some older adults to the level of young adults. This drug effect was linked to restoration of a canonical neural RPE. Our results identify a neurochemical signature underlying abnormal reward processing in older adults and indicate that this can be modulated by L-DOPA.

Research paper thumbnail of Linguistic biomarkers of Hubris syndrome

Cortex, 2013

Shannon entropy Keyness a b s t r a c t Owen and Davidson coined the term 'Hubris Syndrome' (HS) ... more Shannon entropy Keyness a b s t r a c t Owen and Davidson coined the term 'Hubris Syndrome' (HS) for a characteristic pattern of exuberant self-confidence, recklessness, and contempt for others, shown by some individuals holding substantial power. Meaning, emotion and attitude are communicated intentionally through language, but psychological and cognitive changes can be reflected in more subtle ways, of which a speaker remains unaware. Of the fourteen symptoms of HS, four imply lexical choices: use of the third person/'royal we'; excessive confidence; exaggerated self-belief; and supposed accountability to God or History. One other feature (recklessness) could influence language complexity if impulsivity leads to unpredictability. These hypotheses were tested by examining transcribed spoken discourse samples produced by two British Prime Ministers (Margaret Thatcher and Tony Blair) who were said to meet criteria for HS, and one (John Major) who did not. We used Shannon entropy to reflect informational complexity, and temporal correlations (words or phrases whose relative frequency correlated negatively with time in office) and keyness values to identify lexical choices corresponding to periods during which HS was evident. Entropy fluctuated in all three subjects, but consistent (upward) trends in HS-positive subjects corresponded to periods of hubristic behaviour. The first person pronouns 'I' and 'me' and the word 'sure' were among the strongest positive temporal correlates in Blair's speeches. Words and phrases that correlated in the speeches of Thatcher and Blair but not in those of Major included the phrase 'we shall' and 'duties' (both negative). The keyness ratio of 'we' to 'I' was clearly higher throughout the terms of office of Thatcher and Blair that at any point in the premiership of Major, and this difference was particularly marked in the case of Blair. The findings are discussed in the context of historical evidence and ideas for enhancing the signal to noise ratio put forward. ª

Research paper thumbnail of Sight and sound out of synch: Fragmentation and renormalisation of audiovisual integration and subjective timing

Journal homepage: www.elsevier.com/locate/cortex c o r t e x 4 9 ( 2 0 1 3 ) 2 8 7 5 e2 8 8 7

Research paper thumbnail of Corrigendum: Dopamine restores reward prediction errors in old age

Nature Neuroscience, 2014

Research paper thumbnail of Editorial Board

Research paper thumbnail of Confirmation of functional zones within the human subthalamic nucleus: Patterns of connectivity and sub-parcellation using diffusion weighted imaging

Neuroimage, 2012

The subthalamic nucleus (STN) is a small, glutamatergic nucleus situated in the diencephalon. A c... more The subthalamic nucleus (STN) is a small, glutamatergic nucleus situated in the diencephalon. A critical component of normal motor function, it has become a key target for deep brain stimulation in the treatment of Parkinson's disease. Animal studies have demonstrated the existence of three functional sub-zones but these have never been shown conclusively in humans. In this work, a data driven method with diffusion weighted imaging demonstrated that three distinct clusters exist within the human STN based on brain connectivity profiles. The STN was successfully sub-parcellated into these regions, demonstrating good correspondence with that described in the animal literature. The local connectivity of each sub-region supported the hypothesis of bilateral limbic, associative and motor regions occupying the anterior, mid and posterior portions of the nucleus respectively. This study is the first to achieve in-vivo, non-invasive anatomical parcellation of the human STN into three anatomical zones within normal diagnostic scan times, which has important future implications for deep brain stimulation surgery.

Research paper thumbnail of Multiparametric brainstem segmentation using a modified multivariate mixture of Gaussians

NeuroImage: Clinical, 2013

Brainstem Segmentation Modified multivariate mixture of Gaussians Voxel based morphometry Asymmetry

Research paper thumbnail of Characterizing aging in the human brainstem using quantitative multimodal MRI analysis

Frontiers in human neuroscience, 2013

Aging is ubiquitous to the human condition. The MRI correlates of healthy aging have been extensi... more Aging is ubiquitous to the human condition. The MRI correlates of healthy aging have been extensively investigated using a range of modalities, including volumetric MRI, quantitative MRI (qMRI), and diffusion tensor imaging. Despite this, the reported brainstem related changes remain sparse. This is, in part, due to the technical and methodological limitations in quantitatively assessing and statistically analyzing this region. By utilizing a new method of brainstem segmentation, a large cohort of 100 healthy adults were assessed in this study for the effects of aging within the human brainstem in vivo. Using qMRI, tensor-based morphometry (TBM), and voxel-based quantification (VBQ), the volumetric and quantitative changes across healthy adults between 19 and 75 years were characterized. In addition to the increased R2* in substantia nigra corresponding to increasing iron deposition with age, several novel findings were reported in the current study. These include selective volumetr...

Research paper thumbnail of Strategic lacunes and their relationship to cognitive impairment in cerebral small vessel disease

NeuroImage. Clinical, 2014

Lacunes are an important disease feature of cerebral small vessel disease (SVD) but their relatio... more Lacunes are an important disease feature of cerebral small vessel disease (SVD) but their relationship to cognitive impairment is not fully understood. To investigate this we determined (1) the relationship between lacune count and total lacune volume with cognition, (2) the spatial distribution of lacunes and the cognitive impact of lacune location, and (3) the whole brain anatomical covariance associated with these strategically located regions of lacune damage. One hundred and twenty one patients with symptomatic lacunar stroke and radiological leukoaraiosis were recruited and multimodal MRI and neuropsychological data acquired. Lacunes were mapped semi-automatically and their volume calculated. Lacune location was automatically determined by projection onto atlases, including an atlas which segments the thalamus based on its connectivity to the cortex. Lacune locations were correlated with neuropsychological results. Voxel based morphometry was used to create anatomical covarian...

Research paper thumbnail of Dopamine restores reward prediction errors in old age

Nature Neuroscience, 2013

Senescence affects the ability to utilize information about the likelihood of rewards for optimal... more Senescence affects the ability to utilize information about the likelihood of rewards for optimal decision-making. Using functional magnetic resonance imaging in humans, we found that healthy older adults had an abnormal signature of expected value, resulting in an incomplete reward prediction error (RPE) signal in the nucleus accumbens, a brain region that receives rich input projections from substantia nigra/ventral tegmental area (SN/VTA) dopaminergic neurons. Structural connectivity between SN/VTA and striatum, measured by diffusion tensor imaging, was tightly coupled to inter-individual differences in the expression of this expected reward value signal. The dopamine precursor levodopa (L-DOPA) increased the task-based learning rate and task performance in some older adults to the level of young adults. This drug effect was linked to restoration of a canonical neural RPE. Our results identify a neurochemical signature underlying abnormal reward processing in older adults and indicate that this can be modulated by L-DOPA.

Research paper thumbnail of Linguistic biomarkers of Hubris syndrome

Cortex, 2013

Shannon entropy Keyness a b s t r a c t Owen and Davidson coined the term 'Hubris Syndrome' (HS) ... more Shannon entropy Keyness a b s t r a c t Owen and Davidson coined the term 'Hubris Syndrome' (HS) for a characteristic pattern of exuberant self-confidence, recklessness, and contempt for others, shown by some individuals holding substantial power. Meaning, emotion and attitude are communicated intentionally through language, but psychological and cognitive changes can be reflected in more subtle ways, of which a speaker remains unaware. Of the fourteen symptoms of HS, four imply lexical choices: use of the third person/'royal we'; excessive confidence; exaggerated self-belief; and supposed accountability to God or History. One other feature (recklessness) could influence language complexity if impulsivity leads to unpredictability. These hypotheses were tested by examining transcribed spoken discourse samples produced by two British Prime Ministers (Margaret Thatcher and Tony Blair) who were said to meet criteria for HS, and one (John Major) who did not. We used Shannon entropy to reflect informational complexity, and temporal correlations (words or phrases whose relative frequency correlated negatively with time in office) and keyness values to identify lexical choices corresponding to periods during which HS was evident. Entropy fluctuated in all three subjects, but consistent (upward) trends in HS-positive subjects corresponded to periods of hubristic behaviour. The first person pronouns 'I' and 'me' and the word 'sure' were among the strongest positive temporal correlates in Blair's speeches. Words and phrases that correlated in the speeches of Thatcher and Blair but not in those of Major included the phrase 'we shall' and 'duties' (both negative). The keyness ratio of 'we' to 'I' was clearly higher throughout the terms of office of Thatcher and Blair that at any point in the premiership of Major, and this difference was particularly marked in the case of Blair. The findings are discussed in the context of historical evidence and ideas for enhancing the signal to noise ratio put forward. ª

Research paper thumbnail of Sight and sound out of synch: Fragmentation and renormalisation of audiovisual integration and subjective timing

Journal homepage: www.elsevier.com/locate/cortex c o r t e x 4 9 ( 2 0 1 3 ) 2 8 7 5 e2 8 8 7