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Papers by Phil Clatworthy
Scientific Reports, 2020
Behavioural studies investigating the preservation of semantic memory in healthy ageing have repo... more Behavioural studies investigating the preservation of semantic memory in healthy ageing have reported mixed findings. One suggested reason for this discrepancy is that the processes underpinning lexical access to semantic knowledge may be sensitive to ageing. It is therefore necessary to assess semantic memory utilising tasks that are not explicitly linguistic. In this study, a fast periodic visual stimulation (FPVS) paradigm coupled with EEG was used to assess the ability of younger and older adults to automatically distinguish between images by their semantic category. Participants were presented with a 6 Hz stream of images drawn from one semantic category except every fifth image (occurring at a rate of 1.2 Hz) which was drawn from an alternate semantic category. For both younger and older adults, results demonstrate successful and comparable semantic categorisation. This was detectable at the individual level for 71% and 72% of older and younger adults, respectively. Given the ...
Physics in Medicine & Biology, 2019
Apparent diffusion coefficient (ADC) of cerebral water, as measured by diffusion MRI, rapidly dec... more Apparent diffusion coefficient (ADC) of cerebral water, as measured by diffusion MRI, rapidly decreases in ischaemia highlighting a lesion in acute stroke patients. The MRI T2 relaxation time changes in ischaemic brain such that T2 in ADC lesions may be informative of the extent of tissue damage, potentially aiding in stratification for treatment. We have developed a novel user-unbiased method of determining the changes in T2 in ADC lesions as a function of clinical symptom duration based on voxel-wise referencing to a contralateral brain volume. The spherical reference method calculates the most probable pre-ischaemic T2 on a voxel-wise basis, making use of features of the contralateral hemisphere presumed to be largely unaffected. We studied whether T2 changes in the two main cerebral tissue types, i.e. in grey matter (GM) and white matter (WM), would differ in stroke. Thirty-eight acute stroke patients were accrued within 9 hours of symptom onset and scanned at 3T for 3D T1-weighted, multi b-value diffusion and multi-echo spin echo MRI for tissue type segmentation, quantitative ADC and absolute T2 images, respectively. T2 changes measured by the spherical reference method were 1.94 ± 0.61, 1.50 ± 0.52 and 1.40 ± 0.54 ms/hour in the whole, GM and WM lesions, respectively. Thus, T2 time courses were comparable between GM and WM independent of brain tissue type involved. We demonstrate that T2 changes in ADC-delineated lesions can be quantified in the clinical setting in a user unbiased manner and that T2 change correlated with symptom onset time, opening the possibility of using the approach as a tool to assess severity of tissue damage in the clinical setting.
Using a modification of an existing method of probabilistic magnetic resonance tractography analy... more Using a modification of an existing method of probabilistic magnetic resonance tractography analysis, optic radiation images were automatically generated in young healthy subjects, which closely matched histological reference data. Optic radiation loss defined in native space in stroke patients correlated with severity of visual field loss; the strength of the correlation was reduced by visual field recovery, perhaps suggesting underlying brain plasticity. Using a rapid psychophysical method of contrast sensitivity measurement, validated in this study against a criterion-free forced-choice method, contrast sensitivity loss in different regions of the visual field was measured. In the small sample of stroke patients, losses were found both at visual field defect borders, where recovery had likely occurred and, more surprisingly, in the central visual field which appeared never to have been involved in the visual field defect. Finally, using functional magnetic resonance imaging to map the retinotopic organization of the visual areas of the cerebral cortex in the same patients, preliminary evidence was obtained fro visual cortex plasticity, in the form of topographical reorganization in visual area V2 (Brodmann area 18), and in one illustrative patient topographical reorganization of the opposite hemisphere so that V1 contained a representative of the recovered region of visual field. Overall, the study suggests that vision recovers after stroke independent of physical recovery, and this may involve topographical changes in visual cortex. It provides insights into brain structure, function and visual perception following optic radiation stroke, and has generated several tools for further study in this field.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Vision Research, 2003
It is possible to discriminate between grating contrasts over a 300-fold contrast range, whereas ... more It is possible to discriminate between grating contrasts over a 300-fold contrast range, whereas V1 neurons have very limited dynamic ranges. Using populations of model neurons with contrast-response parameters taken from electrophysiological studies (cat and macaque), we investigated ways of combining responses to code contrast over the full range. One model implemented a pooling rule that retained information about individual response patterns. The second summed responses indiscriminately. We measured accuracy of contrast identification over a wide range of contrasts and found the first model to be more accurate; the mutual information between actual and estimated contrast was also greatest for this model. The accuracy peak for the population of cat neurons coincided with the peak of the distribution of contrasts in natural images, suggesting an ecological match. Macaque neurons seem better able to code contrasts that are slightly higher on average than those found in the natural environment.
Journal of Neuroscience, 2009
Previous data suggest that methylphenidate can have variable effects on different cognitive tasks... more Previous data suggest that methylphenidate can have variable effects on different cognitive tasks both within and between individuals. This is thought to be underpinned by inverted U-shaped relationships between cognitive performance and dopaminergic activity in relatively separate fronto-striatal circuits and reflected by individual differences in trait impulsivity. Direct evidence for this is currently lacking. In this study, we demonstrate for the first time that therapeutic doses of oral methylphenidate administered to young healthy subjects result in different sized changes in D 2 /D 3 receptor availability in different regions of the human striatum and that the change in receptor availability within an individual subregion predicts cognitive performance on a particular task. Methylphenidate produced significantly different effects on reversal learning and spatial working memory tasks within individuals. Performance on the reversal learning task was predicted by the drug-induced change in D 2 /D 3 receptor availability in postcommissural caudate, measured using [ 11 C]-raclopride radioligand PET imaging, whereas performance on the spatial working memory task was predicted by changes in receptor availability in the ventral striatum. Reversal learning performance was also predicted by subjects' trait impulsivity, such that the most impulsive individuals benefited more from methylphenidate, consistent with this drug's beneficial effects on cognition in attention deficit hyperactivity disorder.
Journal of the Optical Society of America A, 2003
Individual V1 neurons respond dynamically over only limited ranges of stimulus contrasts, yet we ... more Individual V1 neurons respond dynamically over only limited ranges of stimulus contrasts, yet we can discriminate contrasts over a wide range. Different V1 neurons cover different parts of the contrast range, and the information they provide must be pooled somehow. We describe a probabilistic pooling model that shows that populations of neurons with contrast responses like those in cat and monkey V1 would most accurately code contrasts in the range actually found in natural scenes. The pooling equation is similar to Bayes's equation; however, explicit inclusion of prior probabilities in the inference increases coding accuracy only slightly.
NeuroImage, 2010
Accurately tracing the optic radiations in living humans has important implications for studying ... more Accurately tracing the optic radiations in living humans has important implications for studying the relationship between tract structure or integrity and visual function, in health and disease. Probabilistic tractography is an established method for tracing white matter tracts in humans. Prior studies have used this method to trace the optic radiations, but operator-dependent factors, particularly variability in seed voxel placement and choice of connectivity threshold to select between tract and non-tract voxels, remain potential causes of significant variability. Methods using prior information to modify tract images risk introducing error by underestimating individual variability, particularly in subjects with abnormal anatomy. Finally, existing methods lack thorough validation against a histological standard, causing difficulty in evaluating individual methods, and quantitatively comparing methods. Here we describe a method for producing binary optic radiation images using an existing, well-validated tractography method. All stages are automated, including mask image generation, and thresholds are objectively selected by comparing tract images with existing probabilistic histological data in stereotaxic space. Data from two subject groups are presented; the first used to derive analysis parameters, and the second to test these parameters in an independent sample. Validation utilised a novel variant of receiver operating characteristic analysis, providing both justification for this method and a metric by which tractography methods might be compared generally. The resulting tracts match the histological data well; images generated in individuals matched the histological group data about as well as did images derived in individuals from that histological data set, with a low false positive rate.
Journal of Neurology, Neurosurgery & Psychiatry, 2012
Scientific Reports, 2020
Behavioural studies investigating the preservation of semantic memory in healthy ageing have repo... more Behavioural studies investigating the preservation of semantic memory in healthy ageing have reported mixed findings. One suggested reason for this discrepancy is that the processes underpinning lexical access to semantic knowledge may be sensitive to ageing. It is therefore necessary to assess semantic memory utilising tasks that are not explicitly linguistic. In this study, a fast periodic visual stimulation (FPVS) paradigm coupled with EEG was used to assess the ability of younger and older adults to automatically distinguish between images by their semantic category. Participants were presented with a 6 Hz stream of images drawn from one semantic category except every fifth image (occurring at a rate of 1.2 Hz) which was drawn from an alternate semantic category. For both younger and older adults, results demonstrate successful and comparable semantic categorisation. This was detectable at the individual level for 71% and 72% of older and younger adults, respectively. Given the ...
Physics in Medicine & Biology, 2019
Apparent diffusion coefficient (ADC) of cerebral water, as measured by diffusion MRI, rapidly dec... more Apparent diffusion coefficient (ADC) of cerebral water, as measured by diffusion MRI, rapidly decreases in ischaemia highlighting a lesion in acute stroke patients. The MRI T2 relaxation time changes in ischaemic brain such that T2 in ADC lesions may be informative of the extent of tissue damage, potentially aiding in stratification for treatment. We have developed a novel user-unbiased method of determining the changes in T2 in ADC lesions as a function of clinical symptom duration based on voxel-wise referencing to a contralateral brain volume. The spherical reference method calculates the most probable pre-ischaemic T2 on a voxel-wise basis, making use of features of the contralateral hemisphere presumed to be largely unaffected. We studied whether T2 changes in the two main cerebral tissue types, i.e. in grey matter (GM) and white matter (WM), would differ in stroke. Thirty-eight acute stroke patients were accrued within 9 hours of symptom onset and scanned at 3T for 3D T1-weighted, multi b-value diffusion and multi-echo spin echo MRI for tissue type segmentation, quantitative ADC and absolute T2 images, respectively. T2 changes measured by the spherical reference method were 1.94 ± 0.61, 1.50 ± 0.52 and 1.40 ± 0.54 ms/hour in the whole, GM and WM lesions, respectively. Thus, T2 time courses were comparable between GM and WM independent of brain tissue type involved. We demonstrate that T2 changes in ADC-delineated lesions can be quantified in the clinical setting in a user unbiased manner and that T2 change correlated with symptom onset time, opening the possibility of using the approach as a tool to assess severity of tissue damage in the clinical setting.
Using a modification of an existing method of probabilistic magnetic resonance tractography analy... more Using a modification of an existing method of probabilistic magnetic resonance tractography analysis, optic radiation images were automatically generated in young healthy subjects, which closely matched histological reference data. Optic radiation loss defined in native space in stroke patients correlated with severity of visual field loss; the strength of the correlation was reduced by visual field recovery, perhaps suggesting underlying brain plasticity. Using a rapid psychophysical method of contrast sensitivity measurement, validated in this study against a criterion-free forced-choice method, contrast sensitivity loss in different regions of the visual field was measured. In the small sample of stroke patients, losses were found both at visual field defect borders, where recovery had likely occurred and, more surprisingly, in the central visual field which appeared never to have been involved in the visual field defect. Finally, using functional magnetic resonance imaging to map the retinotopic organization of the visual areas of the cerebral cortex in the same patients, preliminary evidence was obtained fro visual cortex plasticity, in the form of topographical reorganization in visual area V2 (Brodmann area 18), and in one illustrative patient topographical reorganization of the opposite hemisphere so that V1 contained a representative of the recovered region of visual field. Overall, the study suggests that vision recovers after stroke independent of physical recovery, and this may involve topographical changes in visual cortex. It provides insights into brain structure, function and visual perception following optic radiation stroke, and has generated several tools for further study in this field.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Vision Research, 2003
It is possible to discriminate between grating contrasts over a 300-fold contrast range, whereas ... more It is possible to discriminate between grating contrasts over a 300-fold contrast range, whereas V1 neurons have very limited dynamic ranges. Using populations of model neurons with contrast-response parameters taken from electrophysiological studies (cat and macaque), we investigated ways of combining responses to code contrast over the full range. One model implemented a pooling rule that retained information about individual response patterns. The second summed responses indiscriminately. We measured accuracy of contrast identification over a wide range of contrasts and found the first model to be more accurate; the mutual information between actual and estimated contrast was also greatest for this model. The accuracy peak for the population of cat neurons coincided with the peak of the distribution of contrasts in natural images, suggesting an ecological match. Macaque neurons seem better able to code contrasts that are slightly higher on average than those found in the natural environment.
Journal of Neuroscience, 2009
Previous data suggest that methylphenidate can have variable effects on different cognitive tasks... more Previous data suggest that methylphenidate can have variable effects on different cognitive tasks both within and between individuals. This is thought to be underpinned by inverted U-shaped relationships between cognitive performance and dopaminergic activity in relatively separate fronto-striatal circuits and reflected by individual differences in trait impulsivity. Direct evidence for this is currently lacking. In this study, we demonstrate for the first time that therapeutic doses of oral methylphenidate administered to young healthy subjects result in different sized changes in D 2 /D 3 receptor availability in different regions of the human striatum and that the change in receptor availability within an individual subregion predicts cognitive performance on a particular task. Methylphenidate produced significantly different effects on reversal learning and spatial working memory tasks within individuals. Performance on the reversal learning task was predicted by the drug-induced change in D 2 /D 3 receptor availability in postcommissural caudate, measured using [ 11 C]-raclopride radioligand PET imaging, whereas performance on the spatial working memory task was predicted by changes in receptor availability in the ventral striatum. Reversal learning performance was also predicted by subjects' trait impulsivity, such that the most impulsive individuals benefited more from methylphenidate, consistent with this drug's beneficial effects on cognition in attention deficit hyperactivity disorder.
Journal of the Optical Society of America A, 2003
Individual V1 neurons respond dynamically over only limited ranges of stimulus contrasts, yet we ... more Individual V1 neurons respond dynamically over only limited ranges of stimulus contrasts, yet we can discriminate contrasts over a wide range. Different V1 neurons cover different parts of the contrast range, and the information they provide must be pooled somehow. We describe a probabilistic pooling model that shows that populations of neurons with contrast responses like those in cat and monkey V1 would most accurately code contrasts in the range actually found in natural scenes. The pooling equation is similar to Bayes's equation; however, explicit inclusion of prior probabilities in the inference increases coding accuracy only slightly.
NeuroImage, 2010
Accurately tracing the optic radiations in living humans has important implications for studying ... more Accurately tracing the optic radiations in living humans has important implications for studying the relationship between tract structure or integrity and visual function, in health and disease. Probabilistic tractography is an established method for tracing white matter tracts in humans. Prior studies have used this method to trace the optic radiations, but operator-dependent factors, particularly variability in seed voxel placement and choice of connectivity threshold to select between tract and non-tract voxels, remain potential causes of significant variability. Methods using prior information to modify tract images risk introducing error by underestimating individual variability, particularly in subjects with abnormal anatomy. Finally, existing methods lack thorough validation against a histological standard, causing difficulty in evaluating individual methods, and quantitatively comparing methods. Here we describe a method for producing binary optic radiation images using an existing, well-validated tractography method. All stages are automated, including mask image generation, and thresholds are objectively selected by comparing tract images with existing probabilistic histological data in stereotaxic space. Data from two subject groups are presented; the first used to derive analysis parameters, and the second to test these parameters in an independent sample. Validation utilised a novel variant of receiver operating characteristic analysis, providing both justification for this method and a metric by which tractography methods might be compared generally. The resulting tracts match the histological data well; images generated in individuals matched the histological group data about as well as did images derived in individuals from that histological data set, with a low false positive rate.
Journal of Neurology, Neurosurgery & Psychiatry, 2012