David J. Lythgoe

Bio: David J. Lythgoe is an academic researcher from King's College London. The author has contributed to research in topics: Psychosis & Glutamate receptor. The author has an hindex of 32, co-authored 108 publications receiving 3969 citations. Previous affiliations of David J. Lythgoe include University of London & South London and Maudsley NHS Foundation Trust.

Patterns of cerebral blood flow reduction in patients with ischemic leukoaraiosis

Abstract: Background: Ischemic leukoaraiosis (ILA) refers to diffuse T2-weighted white matter hyperintensity in the context of a previous clinical lacunar stroke. Reduced cerebral blood flow (CBF) in white matter has been demonstrated, but it is not known whether hypoperfusion is confined to lesions or extends into normal-appearing white matter. Demonstrating changes in normal-appearing white matter would provide clues to the importance of hypoperfusion in pathogenesis and would be an obvious target for therapies aimed at restoring white matter blood flow. Methods: Twenty-one patients with ILA, and 16 age-matched control subjects, underwent exogenous contrast-based quantitative perfusion MRI. CBF was determined both within and outside areas of T2-weighted hyperintensity in both periventricular white matter and the centrum semiovale. Results: CBF of normal-appearing white matter was reduced in periventricular regions (for patients with ILA, 17.9 ± 5.6 mL/100 g/min; for controls, 21.6 ± 5.1 mL/100 g/min; p = 0.046). CBF in gray matter and normal-appearing white matter of the centrum semiovale did not differ significantly between groups. In normal-appearing white matter in patients, CBF was higher in the centrum semiovale than periventricular white matter, with a similar trend in control subjects. Conclusions: Hypoperfusion may be an early feature in the development of periventricular lesions in ILA and may play a direct pathogenic role. Serial studies are now needed to determine whether these changes herald the appearance of new lesions and represent ‘at risk’ white matter, and to determine whether pharmacological agents can restore perfusion of normal-appearing white matter.

Common and Distinct Neural Substrates for Pragmatic, Semantic, and Syntactic Processing of Spoken Sentences: An fMRI Study

Abstract: Extracting meaning from speech requires the use of pragmatic, semantic, and syntactic information. A central question is: Does the processing of these different types of linguistic information have common or distinct neuroanatomical substrates? We addressed this issue using functional magnetic resonance imaging (fMRI) to measure neural activity when subjects listened to spoken normal sentences contrasted with sentences that had either (A) pragmatical, (B) semantic (selection restriction), or (C) syntactic (subcategorical) violations sentences. All three contrasts revealed robust activation of the left-inferior-temporal/fusiform gyrus. Activity in this area was also observed in a combined analysis of all three experiments, suggesting that it was modulated by all three types of linguistic violation. Planned statistical comparisons between the three experiments revealed (1) a greater difference between conditions in activation of the left-superior-temporal gyrus for the pragmatic experiment than the semantic/syntactic experiments; (2) a greater difference between conditions in activation of the right-superior and middle-temporal gyrus in the semantic experiment than in the syntactic experiment; and (3) no regions activated to a greater degree in the syntactic experiment than in the semantic experiment. These data show that, while left- and right-superior-temporal regions may be differentially involved in processing pragmatic and lexico-semantic information within sentences, the left-inferior-temporal/fusiform gyrus is involved in processing all three types of linguistic information. We suggest that this region may play a key role in using pragmatic, semantic (selection restriction), and subcategorical information to construct a higher representation of meaning of sentences.

Characterization of White Matter Damage in Ischemic Leukoaraiosis with Diffusion Tensor MRI

Abstract: BACKGROUND AND PURPOSE: Information on the neuropathological changes underlying ischemic leukoaraiosis is only available postmortem, and there are limited data on histological appearances early in the disease. Diffusion tensor imaging allows determination of the directionality of diffusion, which is greater in the direction of white matter bundles. Therefore, the technique might be expected to show loss of anisotropy (directional diffusion) in leukoaraiosis. METHODS: Nine patients with ischemic leukoaraiosis (radiological leukoaraiosis and clinical lacunar stroke) and 10 age-matched controls were studied. Diffusion tensor imaging was performed, and maps of diffusion trace and fractional anisotropy were constructed. Mean values of trace and fractional anisotropy were determined in standard regions of the anterior and posterior white matter in both hemispheres. RESULTS: In all patients with ischemic leukoaraiosis, a characteristic abnormal pattern was found, with loss of anisotropy and increased trace in the white matter. For example, in the right anterior white matter mean (SD) trace/3 was 1.12 (0.33) x10(-3) mm2 s-1 in patients and 0.75 (0.11) in controls (P=0.001). In the same region, fractional anisotropy was 0.53 (0.11) in patients and 0.78 (0.09) in controls (P<0.001). Within the white matter regions, there was a strong negative correlation between mean diffusivity and anisotropy (r=-0.92, P<0.0001). CONCLUSIONS: The characteristic pattern found on diffusion tensor imaging in this patient group is consistent with axonal loss and gliosis leading to impairment to and loss of directional diffusion. The "in vivo histological" information obtained may be useful in monitoring disease progression and in investigating the pathogenesis of the cognitive impairment that may be present.

A differential neural response in obsessive-compulsive disorder patients with washing compared with checking symptoms to disgust.

Abstract: Background. Patients with obsessive‐compulsive disorder (OCD) have symptoms that predominantly concern washing (washers) or checking (checkers), or both. Functional neuroimaging has been used to identify the neural correlates of the urge to ritualize but has not distinguished between washing and checking symptoms in OCD. We used functional magnetic resonance imaging to compare the neural response to emotive pictures in washers and checkers. Methods. In one of two 5-minute experiments, washers (N fl 7), checkers (N fl 7) and age-matched normal controls (N fl 14) were scanned while viewing alternating blocks of normally disgusting (rated as disgusting by all subjects) and neutral pictures. In the other experiment, all patients and a normal subgroup (N fl 8) viewed alternating blocks of washer-relevant (rated as more disgusting by washers than normal controls or checkers) and neutral pictures. Results. In all subjects, normally disgusting pictures activated visual regions implicated in perception of aversive stimuli and the insula, important in disgust perception. Only in washers were similar regions activated by washer-relevant pictures. In checkers, these pictures activated frontostriatal regions associated with the urge to ritualize in OCD. Normal controls were more similar in neural response to checkers than washers to these pictures. Both normal controls and checkers had frontal regions activated significantly more by washer-relevant than normally disgusting pictures, and had these regions activated significantly more than washers by washer-relevant pictures. Conclusions. We demonstrate a dierential neural response to washer-relevant disgust in washers and checkers: only washers demonstrate a neural response to washer-relevant disgust associated with emotion perception rather than attention to non-emotive visual detail.

Diffusion tensor imaging: Concepts and applications

Abstract: The success of diffusion magnetic resonance imaging (MRI) is deeply rooted in the powerful concept that during their random, diffusion-driven displacements molecules probe tissue structure at a microscopic scale well beyond the usual image resolution. As diffusion is truly a three-dimensional process, molecular mobility in tissues may be anisotropic, as in brain white matter. With diffusion tensor imaging (DTI), diffusion anisotropy effects can be fully extracted, characterized, and exploited, providing even more exquisite details on tissue microstructure. The most advanced application is certainly that of fiber tracking in the brain, which, in combination with functional MRI, might open a window on the important issue of connectivity. DTI has also been used to demonstrate subtle abnormalities in a variety of diseases (including stroke, multiple sclerosis, dyslexia, and schizophrenia) and is currently becoming part of many routine clinical protocols. The aim of this article is to review the concepts behind DTI and to present potential applications.

Where Is the Semantic System? A Critical Review and Meta-Analysis of 120 Functional Neuroimaging Studies

Abstract: Semantic memory refers to knowledge about people, objects, actions, relations, self, and culture acquired through experience. The neural systems that store and retrieve this information have been studied for many years, but a consensus regarding their identity has not been reached. Using strict inclusion criteria, we analyzed 120 functional neuroimaging studies focusing on semantic processing. Reliable areas of activation in these studies were identified using the activation likelihood estimate (ALE) technique. These activations formed a distinct, left-lateralized network comprised of 7 regions: posterior inferior parietal lobe, middle temporal gyrus, fusiform and parahippocampal gyri, dorsomedial prefrontal cortex, inferior frontal gyrus, ventromedial prefrontal cortex, and posterior cingulate gyrus. Secondary analyses showed specific subregions of this network associated with knowledge of actions, manipulable artifacts, abstract concepts, and concrete concepts. The cortical regions involved in semantic processing can be grouped into 3 broad categories: posterior multimodal and heteromodal association cortex, heteromodal prefrontal cortex, and medial limbic regions. The expansion of these regions in the human relative to the nonhuman primate brain may explain uniquely human capacities to use language productively, plan, solve problems, and create cultural and technological artifacts, all of which depend on the fluid and efficient retrieval and manipulation of semantic knowledge.

The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis

Abstract: Objectives To review the evidence for an association of white matter hyperintensities with risk of stroke, cognitive decline, dementia, and death. Design Systematic review and meta-analysis. Data sources PubMed from 1966 to 23 November 2009. Study selection Prospective longitudinal studies that used magnetic resonance imaging and assessed the impact of white matter hyperintensities on risk of incident stroke, cognitive decline, dementia, and death, and, for the meta-analysis, studies that provided risk estimates for a categorical measure of white matter hyperintensities, assessing the impact of these lesions on risk of stroke, dementia, and death. Data extraction Population studied, duration of follow-up, method used to measure white matter hyperintensities, definition of the outcome, and measure of the association of white matter hyperintensities with the outcome. Data synthesis 46 longitudinal studies evaluated the association of white matter hyperintensities with risk of stroke (n=12), cognitive decline (n=19), dementia (n=17), and death (n=10). 22 studies could be included in a meta-analysis (nine of stroke, nine of dementia, eight of death). White matter hyperintensities were associated with an increased risk of stroke (hazard ratio 3.3, 95% confidence interval 2.6 to 4.4), dementia (1.9, 1.3 to 2.8), and death (2.0, 1.6 to 2.7). An association of white matter hyperintensities with a faster decline in global cognitive performance, executive function, and processing speed was also suggested. Conclusion White matter hyperintensities predict an increased risk of stroke, dementia, and death. Therefore white matter hyperintensities indicate an increased risk of cerebrovascular events when identified as part of diagnostic investigations, and support their use as an intermediate marker in a research setting. Their discovery should prompt detailed screening for risk factors of stroke and dementia.