Biomedical subjects

Adrian M Owen

Publications and source records attributed to Adrian M Owen.

11 recordsLinked to original sources

PubMed2003

Cognitive impairments in early Parkinson's disease are accompanied by reductions in activity in frontostriatal neural circuitry.

Studies in patients with Parkinson's disease (PD) suggest that the characteristic motor symptoms of the disorder are frequently accompanied by impairments in cognition that are most profound in tasks of executive function. Neuropsychological deficits are not an inevitable consequence of the disease, yet the reasons underlying cognitive heterogeneity in PD are not well understood. To determine the underlying neural correlate of these cognitive deficits, we used event-related functional magnetic resonance imaging (fMRI) to compare groups of cognitively impaired and unimpaired patients, matched on all other clinical measures. fMRI revealed significant signal intensity reductions during a working-memory paradigm in specific striatal and frontal lobe sites in patients with cognitive impairment compared with those patients who were not cognitively unimpaired. These results demonstrate that cognitive deficits in PD are accompanied by neural changes that are related to, but distinct from, those changes that underlie motoric deficits in these patients. Furthermore, they suggest that fMRI may provide a valuable tool for identifying patients who may benefit from targeted therapeutic strategies.

Adult↗

PubMed2003

Encoding strategies dissociate prefrontal activity from working memory demand.

It is often proposed that prefrontal cortex is important in organization and control of working memory contents. In some cases, effective reorganization can decrease task difficulty, implying a dissociation between frontal activity and basic memory demand. In a spatial working memory task, we studied the improvement of performance that occurs when materials can be reorganized into higher level groups or chunks. Structured sequences, encouraging reorganization and chunking, were compared with unstructured sequences. Though structured sequences were easier to remember, event-related functional magnetic resonance imaging (fMRI) showed increased activation of lateral frontal cortex, in particular during memory encoding. The results show that, even when memory demand decreases, organization of working memory contents into higher level chunks is associated with increased prefrontal activity.

Adult↗

PubMed2003

Using executive heterogeneity to explore the nature of working memory deficits in Parkinson's disease.

Idiopathic Parkinson's disease (IPD) is characterised by a triad of motor symptoms, namely bradykinesia, rigidity and resting tremor, although cognitive impairment is a common feature of the disease and has been accepted as one of the strong predictors of quality of life in such patients. Neuropsychological testing in Parkinson's disease often reveals a pattern of cognitive impairment similar to that observed in patients with frontal lobe lesions, although clear differences between the two groups have also often been reported. This apparent inconsistency in the literature may reflect heterogeneity among different groups of patients with Parkinson's disease, although to date this possibility has not been formally addressed. In this study, two groups of patients with Parkinson's disease were assessed on a novel verbal memory task, which allowed different aspects of working memory function such as maintenance, retrieval and manipulation to be tested within the same general paradigm. The two groups were selected according to either good or bad performance on a 'standard', visuospatial test of executive function (The Tower of London Task), but were well matched on all other demographic and cognitive measures tested. The sub-group of Parkinson's disease patients with Tower of London defined executive deficit were specifically impaired at manipulating information within verbal working memory, both compared to controls and to the group of patients with no predefined executive impairments. In contrast, the three groups did not differ in their ability to maintain or retrieve information within verbal working memory. Given the known preferential role of the dorsolateral frontal cortex in higher executive functions, (including both planning and the manipulation of information within working memory), these results suggest that, in a subset of Parkinson's disease patients, it is the frontostriatal circuitry involving this region which is primarily affected, while other components of this circuitry may be relatively spared. The results also suggest that performance on the Tower of London task may prove to be a useful discriminant variable in defining the nature of cognitive heterogeneity in Parkinson's disease.

Aged↗

PubMed2002

Regional brain activations differ for semantic features but not categories.

Is human semantic knowledge neurally organised according to either category (e.g. living non-living) or attribute type (e.g. perceptual non-perceptual information)? Normal subjects were scanned using PET during a novel semantic production task, in which they generated either perceptual or non-perceptual information in response to names of living or non-living concepts. Analyses of blood flow in the temporal lobes revealed no significant differences associated with responses to living non-living concepts. Comparisons between retrieval of perceptual non-perceptual information, however, revealed significantly greater blood flow in left posterior inferior temporal cortex and right fusiform cortex associated with perceptual information and in left middle temporal cortex with non-perceptual information. These findings support a primarily attribute-based neural organisation of semantic knowledge.

Adult↗

PubMed2002

Defining the neural mechanisms of probabilistic reversal learning using event-related functional magnetic resonance imaging.

Event-related functional magnetic resonance imaging was used to measure blood oxygenation level-dependent responses in 13 young healthy human volunteers during performance of a probabilistic reversal-learning task. The task allowed the separate investigation of the relearning of stimulus-reward associations and the reception of negative feedback. Significant signal change in the right ventrolateral prefrontal cortex was demonstrated on trials when subjects stopped responding to the previously relevant stimulus and shifted responding to the newly relevant stimulus. Significant signal change in the region of the ventral striatum was also observed on such reversal errors, from a region of interest analysis. The ventrolateral prefrontal cortex and ventral striatum were not significantly activated by the other, preceding reversal errors, or when subjects received negative feedback for correct responses. Moreover, the response on the final reversal error, before shifting, was not modulated by the number of preceding reversal errors, indicating that error-related activity does not simply accumulate in this network. The signal change in this ventral frontostriatal circuit is therefore associated with reversal learning and is uncontaminated by negative feedback. Overall, these data concur with findings in rodents and nonhuman primates of reversal-learning deficits after damage to ventral frontostriatal circuitry, and also support recent clinical findings using this task.

Adult↗

PubMed2002

Preference formation and working memory in Parkinson's disease and normal ageing.

Recent studies in rats have suggested that the amygdala and the dorsal striatum may be differentially involved in the formation of stimulus-reward associations and stimulus-response associations, respectively. In a recent study in humans, conditioned preference learning deficits were observed in a group of patients with damage to the amygdala formation. In this study, patients with Parkinson's disease, which is known to involve pathology of the dorsal striatum, were tested on the same conditioned preference task, together with a group of patients with circumscribed lesions of the frontal lobe. Unlike patients with frontal lobe damage, patients with Parkinson's disease did not exhibit conditioned preferences. However, in this respect their behaviour was indistinguishable from that of age-matched (older) control subjects. In keeping with previous literature, working memory deficits were observed in both patients with Parkinson's disease and patients with frontal-lobe lesions. Compared to young control subjects, a strong increase in preference for familiar, versus novel, items was observed in both patients with Parkinson's disease and in older control subjects. Such a familiarity effect appears to overshadow the conditioning manipulation employed in this task and, therefore, preclude the expression of conditioned preferences in older subjects. These results suggest that there is a developmental progression in the degree to which different mechanisms of 'learning to like' are important over the life span.

Adult↗

PubMed2002

Reading the mind from eye gaze.

Baron-Cohen [Mindblindness: an essay on autism and theory of mind. Cambridge, MA: MIT Press, 1997] has suggested that the interpretation of gaze plays an important role in a normal functioning theory of mind (ToM) system. Consistent with this suggestion, functional imaging research has shown that both ToM tasks and eye gaze processing engage a similar region of the posterior superior temporal sulcus (STS). However, a second brain region associated with ToM, the medial prefrontal (MPF) cortex, has not been identified by previous eye gaze studies. We discuss the methodological issues that may account for the absence of MPF activation in these experiments and present a PET study that controls for these factors. Our experiment included three conditions in which the proportions of faces gazing at, and away from, the participant, were as follows: 100% direct [0% averted], 50% direct-50% averted, and 100% horizontally averted [0% direct]. Two control conditions were also included in which the faces' gaze were averted down, or their eyes were closed. Contrasts comparing the gaze conditions with each of the control conditions revealed medial frontal involvement. Parametric analyses showed a significant linear relationship between increasing proportions of horizontally averted gaze and increased rCBF in the MPF cortex. The opposite parametric analysis (increasing proportions of direct gaze) was associated with increased rCBF in a number of areas including the superior and medial temporal gyri. Additional subtraction contrasts largely confirmed these patterns. Our results demonstrate a considerable degree of overlap between the medial frontal areas involved in eye gaze processing and theory of mind tasks.

Arousal↗

PubMed2002

Evidence for asymmetric frontal-lobe involvement in episodic memory from functional magnetic resonance imaging and patients with unilateral frontal-lobe excisions.

Recently, there has been considerable debate regarding the involvement of the left and right prefrontal cortices in the encoding and retrieval of episodic memory. In a previous PET study, we found that the use of easily verbalisable material may lead to activation predominantly in the left lateral frontal cortex whilst the use of non-easily verbalisable material may lead to activation predominantly in the right lateral frontal cortex, in both cases irrespective of encoding and retrieval processes. In order to replicate and extend these findings, the same task was modified for use with fMRI. Six healthy volunteers were scanned while encoding and then recalling stimuli that either emphasised visual or verbal processes. It was found that, in comparison to a baseline condition, the encoding of visual stimuli led to a bilateral activation of the prefrontal cortex whilst the encoding of verbal stimuli led to a preferential activation of the left prefrontal cortex. An effect of stimulus type was less evident during retrieval, with both visual and verbal stimuli leading to bilateral prefrontal cortex activation. Overall, encoding and retrieval activated similar regions of the prefrontal cortex suggesting that these areas mediate processes that are fundamental to both aspects of memory. To extend these findings further, the tasks used in the fMRI study were used to assess a group of patients with unilateral frontal lesions and a group of healthy control volunteers. The patients were significantly impaired compared to the healthy volunteers, although no significant differences were found in performance between the right- and left-sided lesioned patients. This result suggests that the memory-related asymmetries observed during functional neuroimaging studies may not be critical for task performance.

Female↗

PubMed2002

The problem of functional localization in the human brain.

Functional imaging gives us increasingly detailed information about the location of brain activity. To use this information, we need a clear conception of the meaning of location data. Here, we review methods for reporting location in functional imaging and discuss the problems that arise from the great variability in brain anatomy between individuals. These problems cause uncertainty in localization, which limits the effective resolution of functional imaging, especially for brain areas involved in higher cognitive function.

Brain↗

PubMed2002

Detecting residual cognitive function in persistent vegetative state.

Despite converging agreement about the definition of persistent vegetative state, recent reports have raised concerns about the accuracy of diagnosis in some patients, and the extent to which, in a selection of cases, residual cognitive functions may remain undetected. Objective assessment of residual cognitive function can be extremely difficult as motor responses may be minimal, inconsistent, and difficult to document in many patients, or may be undetectable in others because no cognitive output is possible. Here we describe strategies for using H(2)(15)O positron emission tomography activation studies to study covert cognitive processing in patients with a clinical diagnosis of persistent vegetative state. Three cases are described in detail. Of these, two exhibited clear and predicted regional cerebral blood flow responses during well-documented activation paradigms (face recognition and speech perception) which have been shown to produce specific, robust and reproducible activation patterns in normal volunteers. Some months after scanning, both patients made a significant recovery. In a third case, blood flow data were acquired during a speech perception task, although methodological difficulties precluded any systematic interpretation of the results. In spite of the multiple logistic and procedural problems involved, these results have major clinical and scientific implications and provide a strong basis for the systematic study of possible residual cognitive function in patients diagnosed as being in a persistent vegetative state.

Adult↗

PubMed2002

Dopaminergic modulation of high-level cognition in Parkinson's disease: the role of the prefrontal cortex revealed by PET.

This study examined the effects of L-dopa medication in patients with Parkinson's disease on cortical and subcortical blood flow changes during two tasks known to involve frontostriatal circuitry. Eleven patients with Parkinson's disease were scanned on two occasions, one ON L-dopa medication and one OFF L-dopa medication, during performance of the Tower of London planning task and a related test that emphasized aspects of spatial working memory. L-dopa-induced decreases were observed in the right dorsolateral prefrontal cortex during performance of both the planning and the spatial working memory tasks compared with the visuomotor control task. Conversely, L-dopa-induced blood flow increases were observed in the right occipital lobe during the memory task relative to the control task. Data from age-matched healthy volunteers demonstrated that L-dopa effectively normalized blood flow in these regions in the patient group. Moreover, a significant correlation was found between L-dopa-induced, planning related blood flow decreases in the right dorsolateral prefrontal cortex and L-dopa-induced changes in performance on the planning task. These data suggest that L-dopa ameliorates high-level cognitive deficits in Parkinson's disease by inducing relative blood flow changes in the right dorsolateral prefrontal cortex.

Brain↗