Biomedical subjects

Dominic H ffytche

Publications and source records attributed to Dominic H ffytche.

8 recordsLinked to original sources

PubMed2006

Differences between Alzheimer's disease and dementia with Lewy bodies: an fMRI study of task-related brain activity.

We investigated whether previously reported differences between Alzheimer's disease and dementia with Lewy bodies (DLB) in resting occipital activity lead to activation differences within functionally specialized visual cortical areas and deactivation differences in the default network. Patients with Alzheimer's disease (n = 10; 5 male), DLB (n = 9; 4 male) and controls (n = 13; 5 male) performed three functional MRI (fMRI) scanning experiments involving visual colour, face or motion stimuli. Reaction time or accuracy in DLB and Alzheimer's disease differed significantly from controls but not between patient groups, with the exception of accuracy in the face task (DLB < Alzheimer's disease; P = 0.038). The most significant fMRI activations in the pooled data set were in left V4alpha for the colour task (Talairach coordinate: -30, -52, -24; P = 0.002 corrected), the right fusiform face area (FFA) for the face task (34, -48, -22; P = 0.005 corrected) and right intra-parietal sulcus (30, -66, 42; P = 0.003 corrected) for the motion task, with additional activity in right V5 (48, -64, 0; P = 0.015 corrected). Each task was associated with decreases in activity within the default network with prominent deactivation foci bilaterally in the posterior cingulate gyrus (+/-8, -48, 26; left P < 0.001; right P < 0.001 corrected) and medial frontal cortex (+/-18, 42, 32; left P < 0.001; right P < 0.001 corrected). Comparing patterns of task-related activity across groups, DLB patients showed more activation than Alzheimer patients within the superior temporal sulcus (STS) for the motion task (right STS: 44, 0, -20; P = 0.004 corrected; left STS: -40, -4, -26; P = 0.07 corrected). This difference could not be attributed to task performance, cognitive score or age [analysis of covariance (ANCOVA)F (2, 18) = 8.44, P = 0.003]. Within regions of interest, group activation differences were found for the face task (Alzheimer's disease > DLB P = 0.05; Alzheimer's disease > controls P = 0.14) and the motion task (DLB < Alzheimer's disease P = 0.031 and DLB < control P = 0.048). However, these differences could be explained by behavioural performance, failing to reach significance in the ANCOVA analysis. In the default network, group deactivation differences between controls and both patient groups were found for the colour and motion task (colour: control < Alzheimer's disease P = 0.02; control < DLB P = 0.019; motion: control < Alzheimer's disease P = 0.118; control < DLB P = 0.118) but could be accounted for by behavioural performance. The results suggest that cognitive fMRI can be used to detect both performance-dependent and performance-independent differences between Alzheimer's disease and DLB, reflecting the distribution of functional pathology in the two conditions.

Aged↗

PubMed2006

Evidence against functionalism from neuroimaging of the alien colour effect in synaesthesia.

Coloured hearing synaesthetes experience colours to heard words, as confirmed by reliability of self-report, psychophysical testing and functional neuroimaging data. Some also describe the 'alien colour effect' (ACE): in response to colour names, they experience colours different from those named. We have previously reported that the ACE slows colour naming in a Stroop task, reflecting cognitive interference from synaesthetically induced colours, which depends upon their being consciously experienced. It has been proposed that the hippocampus mediates such consciously experienced conflict. Consistent with this hypothesis, we now report that, in functional magnetic resonance imaging of the Stroop task, hippocampal activation differentiates synaesthetes with the ACE from those without it and from non-synaesthete controls. These findings confirm the reality of coloured hearing synaesthesia and the ACE, phenomena which pose major challenges to the dominant contemporary account of mental states, functionalism. Reductive functionalism identifies types of mental states with causal roles: relations to inputs, outputs and other states. However, conscious mental states, such as experiences of colour, are distinguished by their qualitative properties or qualia. If functionalism is applied to conscious mental states, it identifies the qualitative type of an experience with its causal role or function. This entails both that experiences with disparate qualitative properties cannot have the same functional properties, and that experiences with disparate functional properties cannot have the same qualitative properties. Challenges to functionalism have often denied the first entailment. Here, we challenge the second entailment on empirical grounds. In coloured hearing synaesthesia, colour qualia are associated with both hearing words and seeing surfaces; and, in the ACE, these two functions act in opposition to one another. Whatever its merits as an account of other mental states, reductive functionalism cannot be the correct account of conscious experiences.

Adult↗

PubMed2005

The rises and falls of disconnection syndromes.

In a brain composed of localized but connected specialized areas, disconnection leads to dysfunction. This simple formulation underlay a range of 19th century neurological disorders, referred to collectively as disconnection syndromes. Although disconnectionism fell out of favour with the move against localized brain theories in the early 20th century, in 1965, an American neurologist brought disconnection to the fore once more in a paper entitled, 'Disconnexion syndromes in animals and man'. In what was to become the manifesto of behavioural neurology, Norman Geschwind outlined a pure disconnectionist framework which revolutionized both clinical neurology and the neurosciences in general. For him, disconnection syndromes were higher function deficits that resulted from white matter lesions or lesions of the association cortices, the latter acting as relay stations between primary motor, sensory and limbic areas. From a clinical perspective, the work reawakened interest in single case studies by providing a useful framework for correlating lesion locations with clinical deficits. In the neurosciences, it helped develop contemporary distributed network and connectionist theories of brain function. Geschwind's general disconnectionist paradigm ruled clinical neurology for 20 years but in the late 1980s, with the re-emergence of specialized functional roles for association cortex, the orbit of its remit began to diminish and it became incorporated into more general models of higher dysfunction. By the 1990s, textbooks of neurology were devoting only a few pages to classical disconnection theory. Today, new techniques to study connections in the living human brain allow us, for the first time, to test the classical formulation directly and broaden it beyond disconnections to include disorders of hyperconnectivity. In this review, on the 40th anniversary of Geschwind's publication, we describe the changing fortunes of disconnection theory and adapt the general framework that evolved from it to encompass the entire spectrum of higher function disorders in neurology and psychiatry.

Agnosia↗

PubMed2005

Beyond localization: from hodology to function.

A century on, Campbell's largely forgotten 1905 monograph on the localization of cerebral function has a distinctly contemporary feel. Although his map of cortical fields has been eclipsed by Brodmann's later contribution, Campbell's project went beyond cytoarchitectonic cartography, attempting to integrate clinical, anatomical and physiological evidence to provide a guide to function. A key component of Campbell's integrative, functional anatomical approach was hodology--the pattern of white matter connections between cortical areas--foreshadowing a recently developed functional anatomical technique: diffusion tensor tractography. Here, we revisit Campbell's model of the human visual system using tractography to illustrate prominent white matter connections within the occipital lobe and from occipital to frontal, parietal and temporal regions. Campbell used his integrative approach to support the view that vision consisted of a "visuo-sensory" and a "visuo-psychic" stage, combining hodological, cytoarchitectonic, physiological and clinicopathological evidence to locate the former within the calcarine cortex and the latter within the cortical field surrounding it. Speaking directly to contemporary debates surrounding the neurobiology of conscious vision and providing a framework with which to shape future developments in tractography, Campbell's integrative functional anatomical approach is as relevant today as it was 100 years ago.

Brain Mapping↗

PubMed2005

Perisylvian language networks of the human brain.

Early anatomically based models of language consisted of an arcuate tract connecting Broca's speech and Wernicke's comprehension centers; a lesion of the tract resulted in conduction aphasia. However, the heterogeneous clinical presentations of conduction aphasia suggest a greater complexity of perisylvian anatomical connections than allowed for in the classical anatomical model. This article re-explores perisylvian language connectivity using in vivo diffusion tensor magnetic resonance imaging tractography. Diffusion tensor magnetic resonance imaging data from 11 right-handed healthy male subjects were averaged, and the arcuate fasciculus of the left hemisphere reconstructed from this data using an interactive dissection technique. Beyond the classical arcuate pathway connecting Broca's and Wernicke's areas directly, we show a previously undescribed, indirect pathway passing through inferior parietal cortex. The indirect pathway runs parallel and lateral to the classical arcuate fasciculus and is composed of an anterior segment connecting Broca's territory with the inferior parietal lobe and a posterior segment connecting the inferior parietal lobe to Wernicke's territory. This model of two parallel pathways helps explain the diverse clinical presentations of conduction aphasia. The anatomical findings are also relevant to the evolution of language, provide a framework for Lichtheim's symptom-based neurological model of aphasia, and constrain, anatomically, contemporary connectionist accounts of language.

Adult↗

PubMed2004

Personality predicts brain responses to cognitive demands.

Eysenck (1981) proposed that the personality dimension of introversion- extraversion (E) reflects individual differences in a cortical arousal system modulated by reticulothalamic- cortical pathways: it is chronically more active in introverts relative to extraverts and influences cognitive performance in interaction with task parameters. A circuit with connections to this system, including the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate (AC) cortex, has been identified in studies applying functional magnetic resonance imaging (fMRI) to a broad range of cognitive tasks. We examined the influence of E, assessed with the Eysenck Personality Questionnaire-Revised (Eysenck and Eysenck, 1991), in fMRI activity during an "n-back" task involving four memory loads (0-, 1-, 2-, and 3-back) and a rest condition in healthy men. To confirm the specificity of E effects, we also examined the effects of neuroticism and psychoticism (P) scores. We observed that, as predicted by Eysenck's model, the higher the E score, the greater the change in fMRI signal from rest to the 3-back condition in the DLPFC and AC. In addition, E scores were negatively associated with resting fMRI signals in the thalamus and Broca's area extending to Wernicke's area, supporting the hypothesized (negative) relationship between E and resting arousal. P scores negatively correlated with resting fMRI signal in the globus pallidus-putamen, extending previous findings of a negative relationship of schizotypy to striatal activity seen with older neuroimaging modalities to fMRI. These observations suggest that individual differences affect brain responses during cognitive activity and at rest and provide evidence for the hypothesized neurobiological basis of personality.

Adult↗

PubMed2003

Are neural correlates of visual consciousness retinotopic?

Some visual neurons code what we see, their defining characteristic being a response profile which mirrors conscious percepts rather than veridical sensory attributes. One issue yet to be resolved is whether, within a given cortical area, conscious visual perception relates to diffuse activity across the entire population of such cells or focal activity within the sub-population mapping the location of the perceived stimulus. Here we investigate the issue in the human brain with fMRI, using a threshold stimulation technique to dissociate perceptual from non-perceptual activity. Our results point to a retinotopic organisation of perceptual activity in early visual areas, with independent perceptual activations for different regions of visual space.

Brain Mapping↗

PubMed2003

Cognitive effects of nicotine in humans: an fMRI study.

To elucidate the neural correlates of cognitive effects of nicotine, we examined behavioral performance and blood oxygenation level-dependent regional brain activity, using functional magnetic resonance imaging, during a parametric "n-back" task in healthy nonsmoking males after the administration of nicotine (12 microg/kg body weight) or saline. Nicotine, compared to placebo, improved accuracy (P = 0.008) in all active conditions (2%-11%), and had a load-specific effect on latency (P = 0.004; 43.78% decrease at the highest memory load). Within a network of parietal and frontal areas activated by the task (P < 0.05, corrected at the voxel level), nicotine produced an increased response (P < 0.05; uncorrected within the regions of interest) in the anterior cingulate, superior frontal cortex, and superior parietal cortex. It also produced an increased response in the midbrain tectum in all active conditions and in the parahippocampal gyrus, cerebellum, and medial occipital lobe during rest (P = 0.05; uncorrected). The present observations point to altered neuronal activity in a distributed neural network associated with on-line task monitoring and attention and arousal systems as underlying nicotine-related enhancement of attention and working memory in human subjects.

Adult↗