Papers by William Rodman Shankle
Methods of Information in Medicine, 2001
Summary Objectives: The aim was to evaluate the potential for monotonicity constraints to bias ma... more Summary Objectives: The aim was to evaluate the potential for monotonicity constraints to bias machine learning systems to learn rules that were both accurate and meaningful. Methods: Two data sets, taken from problems as diverse as screening for dementia and assessing the risk of mental retardation, were collected and a rule learning system, with and without monotonicity constraints, was run on each. The rules were shown to experts, who were asked how willing they would be to use such rules in practice. The accuracy of the rules was also evaluated. Results: Rules learned with monotonicity constraints were at least as accurate as rules learned without such constraints. Experts were, on average, more willing to use the rules learned with the monotonicity constraints. Conclusions: The analysis of medical databases has the potential of improving patient outcomes and/or lowering the cost of health care delivery. Various techniques, from statistics, pattern recognition, machine learning,...
Journal of Alzheimer S Disease Jad, Dec 12, 2012
Alzheimers Dement, 2011
Background: Posterior cortical atrophy (PCA) is a degenerative condition characterised by progres... more Background: Posterior cortical atrophy (PCA) is a degenerative condition characterised by progressive visual dysfunction and atrophy of the parietal and occipital lobes, most commonly due to Alzheimer's disease (Lehmann et al., 2009, Tang-Wai et al., 2004). Experiments investigating PCA typically use pencil and paper tests, where the connection between test results and real world ability is unclear. The present experiment aimed to improve our understanding of patients' visual deficits in a more naturalistic context using pictures of faces, scenes and objects. The use of color as a cue was also assessed as this can be relatively spared in PCA (Lehmann et al, in press). Methods: Participants were 20 patients with a clinical diagnosis of PCA due to probable Alzheimer's disease. A background neuropsychological battery including tests of memory, visual acuity and color perception was completed. Three types of stimuli were chosen; faces (Minear & Park, 2004, Tottenham et al., 2009), scenes and objects (see Figure 1a). Each had two categories, and each category had three forced choice options. For example in the aged faces category, the choices were 'young' 'middle aged' or 'old'. Participants responded verbally. Reaction time data was used only when accuracy was greater than 80%, and included correct trials only. Results: Pilot data has been collected from four participants; we hope to complete data collection by April 2011. Average categorization performance was more accurate for color than grayscale images (color: 89.7%, RT 3.1s; grayscale 84.7%, 4.1s). However, for some individuals the magnitude and direction of the color effect differed between stimulus categories. Whilst the majority of patients showed equivalent deficits, some patients showed greater deficits in certain categories (see Figure 1b). Conclusions: The results demonstrate a difference in performance between colour and grayscale conditions, particularly in the object and scene categories where colour contains strong cues. This study demonstrates heterogeneity in the face, object and scene perception abilities of PCA patients. Dissociations in performance between categories and colour/grayscale conditions are likely to reflect variation in the loci of greatest atrophy. This has implications for management of visual deficits in PCA and the design of visual aids to improve everyday functional ability.
Journal of Alzheimer's disease : JAD, 2013
Aggregates of hyperphosphorylated tau (PHF-tau), such as neurofibrillary tangles, are linked to t... more Aggregates of hyperphosphorylated tau (PHF-tau), such as neurofibrillary tangles, are linked to the degree of cognitive impairment in Alzheimer's disease. We have developed a novel PHF-tau targeting positron emission tomography imaging agent, [F-18]-T807, which may be useful for imaging Alzheimer's disease and other tauopathies. Here in, we describe the first human brain images with [F-18]-T807.
Clinical EEG and neuroscience, 2005
In this study, we hypothesized that a quantitative EEG (qEEG) method for measuring EEG variabilit... more In this study, we hypothesized that a quantitative EEG (qEEG) method for measuring EEG variability combined with specific psychophysical tasks could improve the classification accuracy of subjects with normal aging vs. mild cognitive impairment (MCI) or mild dementia due to Alzheimer's Disease and Related Disorders (ADRD). The cross-sectional sample consisted of 48 subjects (32 normal aging and 16 ADRD: n = 3 mild dementia, n = 13 MCI FAST stage 3). During EEG recording, subjects performed two visual, delayed recognition memory tasks as well as a task that tested their ability to perceive structure-from-motion (SFM). These EEG data were used to compute qEEG measures of the (normalized) variance of posterior cortical activity during the first 150 milliseconds (ms) after stimulus onset and the variance of anterior cortical activity during the second 150 ms epoch. The ratio, anterior/posterior cerebral qEEG value, was then computed for each subject, and the optimal cutoff value ide...
Electrophoresis
The determination of inorganic cations and anions by capillary electrophoresis/mass spectrometry ... more The determination of inorganic cations and anions by capillary electrophoresis/mass spectrometry (CE/MS) is reported using an ion spray-sheath flow interface coupling. A twelve-component synthetic mixture of cations which included the positive ions of K, Ba, Ca, Mn, Cd, Co, Pb, Cr, Ni, Zn, Ag, and Cu was loaded into the capillary column at levels ranging from 30 to 300 pg, separated by CE, and detected by indirect UV and in the full-scan (m/z 35-450) positive ion CE/MS mode using an aqueous buffer containing 30 mM creatinine and 8 mM alpha-hydroxyisobutyric acid, pH 4.8. Creatinine forms adducts with the cations which are observed in the gas phase and requires rather high (120 electron volts) declustering energy to dissociate. This produces a reduction in charge state to form the free, singly charged, inorganic cations which are observed in the mass spectra. CE/MS analysis of an aqueous acidic extract of used aircraft engine oil revealed high levels of lead as well as lower levels o...
NeuroReport, 1994
Dynamic MR imaging has revealed dramatic fluctuations in the appearance of CSF in the cortical su... more Dynamic MR imaging has revealed dramatic fluctuations in the appearance of CSF in the cortical sulci and cortical subarachnoid spaces in aging individuals and patients with hydrocephalus, dementia and Down syndrome in contrast to young healthy volunteers. The changes have been interpreted as volume fluctuations that represent undamped CSF hydrodynamics and have implications with respect to the origin of CSF in the cortical regions and with respect to the similarity between aging and dementia and edematous states of the brain.
Neurological Research, 2008
Neurological Research, 2009
Omentum transposition surgery (OT) applied to various neurodegenerative disorders has produced cl... more Omentum transposition surgery (OT) applied to various neurodegenerative disorders has produced clinically significant improvement, which may be due to omentally-derived factors. To evaluate the clinical effect of left hemisphere OT in a primary progressive aphasia (PPA) patient, 3 year follow-up data were analysed. Left hemisphere OT was performed on a 68-year-old male with PPA, characterized by moderate dementia and severe expressive aphasia with relatively preserved comprehension, object recognition and visual-spatial abilities. He was longitudinally assessed with cognitive, functional, behavioral and brain HMPAO SPECT measures pre-OT, at baseline and every 3-6 months for 34 months. All measures improved above baseline for >20 months and persisted at or above baseline for 34 months. Cortical activity increased by a maximum of 21% underneath transposed omentum and in synaptically connected areas, and persisted in >50% of the cortex for at least 12 months. Subjectively, family members observed improved verbal and non-verbal communication. OT produced a sustained, beneficial treatment effect in PPA and warrants further clinical and basic research to identify explanatory factors.
Neurobiology of Aging, 2004
Journal of Theoretical Biology, 1998
The generalization of the finding of no postnatal neurogenesis in non-human primates to humans ma... more The generalization of the finding of no postnatal neurogenesis in non-human primates to humans may be incorrect because: (1) rhesus macaques belong to a superfamily that diverged more than 25 million years ago from the superfamily including the genus Homo; (2) the pulse thymidine labeling method, which demonstrates DNA synthesis rather than mitosis per se, is less reliable than some have assumed. This study examines changes in the number of neurons in a column underneath a cortical surface area of 1 mm2, extending through all cortical layers (mm2-column) for 35 gyri (representing about 73% of the human cerebral cortex) based on the data of J.L. Conel (1939 to 1967). We corrected these data, derived from his measures of cortical neuronal packing density, somal breadth and height, and cortical layer thickness at postnatal ages 0, 1, 3, 6, 15, 24, 48, and 72 months, for shrinkage and stereological errors. In all 35 gyri, neuron number/mm2-column: (1) initially declines (mu = 46% decline, sigma = 8%), 95% of which is due to surface area expansion (mean age of nadir value = 15.8 months); (2) then increases to age 72 months by 70% (mu = 1.7-fold increase, (mu rate = 1.1% per month). Because of a a concomitant 1.3-fold increase in cortical surface from 15 to 72 months, total cortical neuron number increases 2.2-fold. The close agreement between neuron number/mm2-column for Conel's age 72-month data to the corresponding values reported by others for adult human and primate cortex using more modern methods suggests the finding is not an artifact. Neuronal proliferative fate-determining factors provide at least four mechanisms for increasing cortical neuron number postnatally, with or without DNA synthesis.
Journal of Mathematical Psychology, 2011
ABSTRACT The study of human episodic memory is a topic that interests cognitive and mathematical ... more ABSTRACT The study of human episodic memory is a topic that interests cognitive and mathematical psychologists as well as clinicians interested in the diagnosis and assessment of Alzheimer’s disease and related disorders (ADRD). In this paper, we use simple cognitive models for the recognition and recall tasks typically applied in clinical assessments of ADRD to study memory performance in ADRD patients. Our models make use of hierarchical Bayesian methods as a way to model individual differences in patient performance and to facilitate the modeling of performance changes that occur during multiple recall tasks. We show how the models are able to account for different aspects of patient performance, and also discuss some of the predictive capabilities of the model. We conclude with a discussion on the scope to improve on our results by discussing the link between memory theory in psychology and clinical practice.
Fetal & Pediatric Pathology, 1983
This study subjects the Coppoletta-Wolbach data of normal organ weights of children from birth to... more This study subjects the Coppoletta-Wolbach data of normal organ weights of children from birth to 12 years of age to statistical analysis, producing a set of curves that show the linear regression of organ weight versus age for each set of weights plus, for each organ, the 75%, 80%, 90%, 95%, and 99% confidence bands for single new values.
Clinical Neurophysiology, 2002
Objectives: To test the hypothesis that elecetroencephalographic (EEG) analysis is sensitive to c... more Objectives: To test the hypothesis that elecetroencephalographic (EEG) analysis is sensitive to cortical neuronal impairment in early stage Alzheimer's disease (AD), and that this analysis correlates with corresponding changes in cerebral blood flow. Methods: We examined an EEG measure of neuronal impairment in the cerebral cortex in terms of its ability to detect very mild AD. This measure, the mean value of the resting state EEG alpha dipolarity (D a), approaches unity without cortical sulcal lesions, whereas brains with randomly distributed cortical sulcal lesions lower D a values well below unity. D a was evaluated in 25 patients with very mild AD, 33 patients with moderately severe AD, and 56 normal age-matched subjects. These subjects also received SPECT, and strong correlation between D a and regional cerebral blood flow (rCBF) was observed. Results: D a values greater than 0.977 correctly classified normal subjects, but also included 10% of very mild AD. D a values less than 0.952 correctly classified very mild AD as well as moderately severe AD, but also included 10% of normal subjects. D a values also correlated positively with bilateral temporal-parietal rCBF (a characteristic finding in AD patients); both declined with increasing dementia severity. Conclusions: Analysis of D a in this sample supports the hypothesis that early stages of AD can be discriminated from normal aging using measures of cortical neuronal impairment. Furthermore, dementia severity, as reflected by the degree of impairment, is reflected in declining D a values and increasing variance (greater spread of the D a values).
Clinical EEG and Neuroscience, 2006
Previous research has shown that quantitative electroencephalography (qEEG) can monitor treatment... more Previous research has shown that quantitative electroencephalography (qEEG) can monitor treatment of Alzheimer's Disease (AD). This study investigated the ability of a qEEG measure based on EEG variance, combined with a delayed recognition memory task, to measure treatment effects on patients with AD. Three AD patients with very mild AD (CDR=0.5, FAST stage 3) were monitored with task specific EEG at multiple time points before and after medication treatment. Patients had their EEG recorded while performing a recognition memory task. A measure of (normalized) variance was applied to the EEG data. To the extent possible, the subjects received this treatment monitoring multiple times. These patients were monitored a total of 14 times, which yielded 11 measurements of qEEG change during the course of treatment. The direction of change in patients' qEEG values agreed with patients' medication treatment on 10 out of 11 occasions, p < 0.006 (binomial test) and was more accurate than monitoring with the relative theta power, p < 0.05. The results of this monitoring also showed that the qEEG measure accurately reflected treatment in a dose dependent manner. These results were independent of the specific medication monitored; Galantamine, Memantine, Nicotine, and Rivastigmine. In conclusion, this qEEG method may be useful for measuring AD treatment responses.
Brain and Cognition, 1995
Archives of Neurology, 2012
... Results of recognition memory experiments (eg, Mickes, Wixted, & Wais, 2007), however, su... more ... Results of recognition memory experiments (eg, Mickes, Wixted, & Wais, 2007), however, support a version of SDT in which the standard deviation of the old distribution is 25% larger than the standard deviation of the new distri-bution, so that σnew/σold = 0.8. ...
Alzheimer's & Dementia, 2012
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Papers by William Rodman Shankle