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Biomedical subjects

A M Owen

Publications and source records attributed to A M Owen.

At least 19 recordsLinked to original sources
PubMed2000

Impaired preference conditioning after anterior temporal lobe resection in humans.

Research with animals suggests that structures within the amygdaloid nuclear complex (ANC) are critical for acquiring associations between rewarding events and neutral stimuli, a form of conditioning often manifested in a subsequent preference for those (conditioned) stimuli. In this study, we investigated the relationship between the ANC and preference learning in humans. Three abstract monochrome patterns were presented to each subject over 180 trials in the context of a counting task requiring working memory. One pattern was paired with food reward on 90% of the trials in which it was presented and with no food reward on the other 10% of trials. The other patterns were similarly reinforced, but at ratios of 50:50% and 10:90% with reward and nonreward, respectively. Subsequently, a group of 21 normal participants preferred the pattern paired most often with reward to that paired least often with reward, and they did not explicitly relate their preferences to the conditioning procedure, but instead attributed them to the characteristics of the patterns themselves. Unlike the normal controls, a group of patients with unilateral surgical lesions that included the ANC (15 left, 18 right) did not show conditioned preferences, but performed normally on a measure of working memory. In contrast, 13 patients with unilateral damage confined to frontal cortex exhibited normal conditioned preferences but were impaired on the working memory task. This double dissociation provides clear evidence that, in humans as in other animals, reward-related learning (conditioned reward) critically depends on a circuit involving inferotemporal cortex and the ANC.

Adolescent↗
PubMed2000

Methylphenidate enhances working memory by modulating discrete frontal and parietal lobe regions in the human brain.

The indirect catecholamine agonist methylphenidate (Ritalin) is the drug treatment of choice in attention deficit/hyperactivity disorder (AD/HD), one of the most common behavioral disorders of childhood (DSM-IV), although symptoms may persist into adulthood. Methylphenidate can enhance cognitive performance in adults and children diagnosed with AD/HD (Kempton et al., 1999; Riordan et al., 1999) and also in normal human volunteers on tasks sensitive to frontal lobe damage, including aspects of spatial working memory (SWM) performance (Elliott et al., 1997). The present study investigated changes in regional cerebral blood flow (rCBF) induced by methylphenidate during performance of a self-ordered SWM task to define the neuroanatomical loci of the beneficial effect of the drug. The results show that the methylphenidate-induced improvements in working memory performance occur with task-related reductions in rCBF in the dorsolateral prefrontal cortex and posterior parietal cortex. The beneficial effects of methylphenidate on working memory were greatest in the subjects with lower baseline working memory capacity. This is to our knowledge the first demonstration of a localization of a drug-induced improvement in SWM performance in humans and has relevance for understanding the treatment of AD/HD.

Adrenergic Uptake Inhibitors↗
PubMed2000

Activity in ventrolateral and mid-dorsolateral prefrontal cortex during nonspatial visual working memory processing: evidence from functional magnetic resonance imaging.

Whole-brain functional magnetic resonance imaging was used to study five healthy human subjects while they performed two nonspatial visual working memory tasks and one control task. In the first memory task, the subjects were required to view a sequence of three pattern stimuli, randomly selected from a familiar set of four stimuli, and then identify which one of three simultaneously presented stimuli was the one that had not been presented in the previous array. In the other task, the subjects were required to observe an identical sequence of three randomly selected pattern stimuli and then to respond by selecting those same stimuli in the order presented. In comparison to a baseline control task, increases in signal intensity were observed, bilaterally, in the mid-dorsolateral frontal cortex and in the right ventrolateral frontal cortex in both memory tasks. When the two tasks were compared directly, however, the first memory task, which had the higher monitoring requirement, yielded significantly greater signal intensity changes in area 9/46 of the right mid-dorsolateral frontal cortex. These results provide further evidence for the precise functional contribution made by the mid-dorsolateral frontal cortex in visual working memory tasks and concur closely with findings in nonhuman primates.

Adult↗
PubMed2000

The role of the lateral frontal cortex in mnemonic processing: the contribution of functional neuroimaging.

Evidence is now converging which suggests that, at the area level, working-memory processes within the dorsolateral and ventrolateral frontal cortices are organised according to the type of processing required, rather than according to the nature (i.e. domain) of the information being processed, as has been widely assumed. In a recent study using functional magnetic-resonance imaging (fMRI), performance of visual spatial and visual non-spatial working-memory tasks was shown to involve identical regions of the lateral prefrontal cortex when all factors unrelated to the type of stimulus material were appropriately controlled. These results concur fully with recent reviews of the imaging literature, which demonstrate that spatial, visuospatial and verbal working-memory studies have produced distributed patterns of overlapping activation foci within these lateral frontal regions. Moreover, two recent positron-emission tomography studies have demonstrated that either, or both, the ventrolateral and dorsolateral frontal regions can be activated in spatial working-memory tasks, depending on the precise executive processes that are called upon by the task being performed. Similarly, when the executive requirements of a simple verbal working-memory task (e.g. forwards versus backwards digit span) are manipulated, differential activation within these two frontal cortical areas is observed. The results provide further evidence that the mid-dorsolateral and mid-ventrolateral frontal cortical areas make distinct "executive" contributions to memory and correspond with a fractionation of working-memory processes in psychological terms.

Frontal Lobe↗
PubMed2000

Asymmetric frontal activation during episodic memory: the effects of stimulus type on encoding and retrieval.

Recent functional neuroimaging studies have suggested that the left prefrontal cortex is preferentially involved in the encoding of episodic memory whilst the right prefrontal cortex is preferentially involved in the retrieval of episodic memory, irrespective of the type (e.g. modality) of information being remembered. In the present PET activation study, a 2 x 2 design was employed to investigate the relationship between encoding and retrieval of verbal and non-verbal material in episodic memory. Accordingly, seven healthy volunteers were scanned whilst encoding and then recalling stimuli which either emphasised visual or verbal processes. When encoding and retrieval tasks were compared directly, significantly greater prefrontal activation was observed in the encoding conditions, regardless of modality, although these changes were bilaterally distributed. In contrast when the verbal and visual memory tasks were compared directly, the former was associated with rCBF changes that were predominantly located in the left lateral frontal cortex whilst the latter was associated with rCBF changes that were predominantly located in the right lateral frontal cortex. These results suggest that encoding and retrieval may actually involve similar regions of the lateral prefrontal cortex when all factors relating to the type of stimulus material (i.e. modality), are appropriately controlled.

Adult↗
PubMed2000

Common regions of the human frontal lobe recruited by diverse cognitive demands.

Though many neuroscientific methods have been brought to bear in the search for functional specializations within prefrontal cortex, little consensus has emerged. To assess the contribution of functional neuroimaging, this article reviews patterns of frontal-lobe activation associated with a broad range of different cognitive demands, including aspects of perception, response selection, executive control, working memory, episodic memory and problem solving. The results show a striking regularity: for many demands, there is a similar recruitment of mid-dorsolateral, mid-ventrolateral and dorsal anterior cingulate cortex. Much of the remainder of frontal cortex, including most of the medial and orbital surfaces, is largely insensitive to these demands. Undoubtedly, these results provide strong evidence for regional specialization of function within prefrontal cortex. This specialization, however, takes an unexpected form: a specific frontal-lobe network that is consistently recruited for solution of diverse cognitive problems.

Animals↗
PubMed2000

Maintaining and shifting attention within left or right hemifield.

Positron emission tomography (PET) was used to examine two questions: (i) which structures of the intact human brain change their activity with the direction of attention to left or right visual field; and (ii) how does activity in these structures, and in parietal cortex in particular, depend on the frequency of attentional shifts? Subjects were required to discriminate the orientation of peripheral gratings. The two main experimental variables were the attended hemifield (left or right) and the proportion of trials requiring a shift within that hemifield (20% or 80%). A detection control condition was also included. Behaviourally, subjects were less accurate and significantly slower when a trial required a shift than when it did not. Ventral and lateral occipital areas showed significantly higher blood flow levels contralateral to the direction of attention. Replicating previous work, there was also a significant main effect of the direction of attention in left lateral prefrontal cortex: blood flow levels were higher during leftward attention in comparison both to baseline and to rightward attention. This left frontal effect reached significance in single subjects in whom several activation sites could be distinguished within left middle and inferior frontal gyrus. Right and left parietal cortex were activated during both left- and right-field attention conditions, with a tendency for higher activity levels when attention was directed contralaterally. Contrary to the experimental hypothesis, however, parietal regions were not activated differentially by high versus low numbers of attentional shifts. The current experiment confirms that left frontal convexity is sensitive to manipulations of the direction of visuospatial attention. The results do not indicate a specific role of parietal cortex in attentional shifting.

Adult↗
PubMed1999

Choosing between small, likely rewards and large, unlikely rewards activates inferior and orbital prefrontal cortex.

Patients sustaining lesions of the orbital prefrontal cortex (PFC) exhibit marked impairments in the performance of laboratory-based gambling, or risk-taking, tasks, suggesting that this part of the human PFC contributes to decision-making cognition. However, to date, little is known about the particular regions of the orbital cortex that participate in this function. In the present study, eight healthy volunteers were scanned, using H(2)(15)0 PET technology, while performing a novel computerized risk-taking task. The task involved predicting which of two mutually exclusive outcomes would occur, but critically, the larger reward (and penalty) was associated with choice of the least likely outcome, whereas the smallest reward (and penalty) was associated with choice of the most likely outcome. Resolving these "conflicting" decisions was associated with three distinct foci of regional cerebral blood flow increase within the right inferior and orbital PFC: laterally, in the anterior part of the middle frontal gyrus [Brodmann area 10 (BA 10)], medially, in the orbital gyrus (BA 11), and posteriorly, in the anterior portion of the inferior frontal gyrus (BA 47). By contrast, increases in the degree of conflict inherent in these decisions was associated with only limited changes in activity within orbital PFC and the anterior cingulate cortex. These results suggest that decision making recruits neural activity from multiple regions of the inferior PFC that receive information from a diverse set of cortical and limbic inputs, and that the contribution of the orbitofrontal regions may involve processing changes in reward-related information.

Adult↗
PubMed1999

Comparison of set-shifting ability in patients with chronic schizophrenia and frontal lobe damage.

Neuropsychological studies of patients with schizophrenia have consistently identified deficits on tests sensitive to frontal lobe function. One paradigm that has been widely used is that of attentional set-shifting using the Wisconsin Card Sorting Test (WCST). In the present study, patients with chronic schizophrenia and with frontal lobe lesions were assessed on a computerised set-shifting task that provides a componential analysis of the WCST by distinguishing between intra-dimensional and extra-dimensional set-shifting. Out of 51 patients with schizophrenia, those with high IQ (n =24) were compared with patients with lesions in prefrontal cortex (n = 22) and with normal control subjects (n= 18). These three groups were well matched for age, sex and National Adult Reading Test (NART) IQ. The schizophrenic group showed a significantly higher rate of attrition at the intra-dimensional shift stage of learning compared with the other two groups. At the extra-dimensional shift stage, both the schizophrenic and frontal lesioned groups showed greater attrition than controls. Further, patients with schizophrenia who were able to learn the intradimensional reversal stage required more trials and made significantly more errors at that stage than the other two groups. In comparison with high IQ patients with schizophrenia, those with low IQ performed at a lower level but showed a qualitatively similar pattern of performance, providing further evidence that the set-shifting deficits were not simply explained by any global intellectual decline. Patients with schizophrenia who dropped out at the extradimensional shift stage had higher negative symptom scores compared with patients dropping out at previous learning stages, while patients failing at the intra-dimensional shift stage had lower scores for bradyphrenia (slowness of thought). The results suggest that patients with chronic schizophrenia fail to 'learn set' and are impaired at both set-shifting and concept formation. The relevance of these findings to understanding the nature of prefrontal cortical deficits in chronic schizophrenia is discussed. The implication of these findings to the rehabilitation of these patients is considered.

Adult↗
PubMed1999

A cognitive activation study of memory for spatial relationships.

Twelve neurologically normal right-handed subjects were asked to remember the locations of eight representational drawings, presented one at a time, together with two landmarks (white squares), on a computer screen. Subjects were then scanned using positron emission tomography (PET) while performing forced-choice recognition of object location in four conditions, using either the original landmarks or two of the other objects as cues. In two conditions, the absolute location of the objects was unchanged from the time of encoding (fixed-array conditions), whereas in the other two, the location of the objects was shifted, although the spatial relationship among the objects and landmarks was maintained (shifted-array conditions). Subjects were also scanned in a control condition that made the same perceptual and motor demands as the recognition tasks but that had no mnemonic component. Compared to the control condition, all of the recognition tasks activated both the dorsal and ventral visual pathways bilaterally, but with notable asymmetries. In particular, activation in the right, but not left, inferior temporal gyrus (area 37) was observed when both shifted-array conditions were compared to their respective cue-matched fixed-array conditions. The recognition conditions with landmark cues were associated with focal increases in regional cerebral blood flow (rCBF) in the region of the right parahippocampal gyrus. The results support previous reports of involvement of the right mesial temporal region in object-location memory tasks, and suggest that right inferotemporal cortex is involved in extracting the invariant relational features of a visual scene.

Adult↗
PubMed1999

Redefining the functional organization of working memory processes within human lateral prefrontal cortex.

It is widely held that the frontal cortex plays a critical part in certain aspects of spatial and non-spatial working memory. One unresolved issue is whether there are functionally distinct subdivisions of the lateral frontal cortex that subserve different aspects of working memory. The present study used positron emission tomography (PET) to demonstrate that working memory processes within the human mid-dorsolateral and mid-ventrolateral frontal regions are organized according to the type of processing required rather than according to the nature (i.e. spatial or non-spatial), of the information being processed, as has been widely assumed. Two spatial working memory tasks were used which varied in the extent to which they required different executive processes. During a 'spatial span' task that required the subject to hold a sequence of five previously remembered locations in working memory a significant change in blood-flow was observed in the right mid-ventrolateral frontal cortex, but not in the anatomically and cytoarchitectonically distinct mid-dorsolateral frontal-lobe region. By contrast, during a '2-back' task that required the subject to continually update and manipulate an ongoing sequence of locations within working memory, significant blood flow increases were observed in both mid-ventrolateral and mid-dorsolateral frontal regions. When the two working memory tasks were compared directly, the one that emphasized manipulation of information within working memory yielded significantly greater activity in the right mid-dorsolateral frontal cortex only. This dissociation provides unambiguous evidence that the mid-dorsolateral and mid-ventrolateral frontal cortical areas make distinct functional contributions to spatial working memory and corresponds with a fractionation of working memory processes in psychological terms.

Adult↗
PubMed1999

Mapping the network for planning: a correlational PET activation study with the Tower of London task.

We used the Tower of London task (TOL) and H(2)(15)O-PET to map the network of brain structures involved in planning. Six healthy right-handed subjects had 12 measurements of relative regional cerebral blood flow (rrCBF) during six conditions, each performed twice. There was one rest condition, and five sets of TOL problems at different complexity levels, performed on a touch-sensitive computer monitor with the right arm. Complexity was defined as the number of moves required to solve each problem. Activation was analysed in two ways: a category analysis comparing levels of rrCBF during rest and task was done to identify all structures involved in performance of the TOL; and a correlation analysis was carried out to delineate a subset of structures where the levels of rrCBF correlated with task complexity. Activated brain areas in which rrCBF increases did not correlate with complexity could be grouped into: (i) regions belonging to the dorsal stream of visual input processing, namely visual cortical areas 17, 18 and 19, and posterior parietal cortical areas 7 and 40; and (ii) regions involved in the execution and sequencing of arm movements (right cerebellum, left primary motor cortex and supplementary motor area). Brain regions where levels of rrCBF correlated with task complexity included lateral premotor cortex (area 6), rostral anterior cingulate cortex (areas 32 and 24), dorsolateral prefrontal cortex (areas 9 and 46) bilaterally, and right dorsal caudate nucleus. We propose that dorsolateral prefrontal, lateral premotor, anterior cingulate and caudate areas form a network for the planning of movement that interacts with brain areas primarily involved in visual processing and movement execution.

Aged↗
PubMed1998

Memory: dissociating multiple memory processes.

Memory depends upon a network of interconnected and functionally related cortical and subcortical areas including, at the very least, the prefrontal cortex and the medial temporal lobe structures. Evidence is now emerging to relate these neuroanatomical regions to specific aspects of mnemonic processing.

Animals↗
PubMed1998

Functional organization of spatial and nonspatial working memory processing within the human lateral frontal cortex.

The present study used functional magnetic resonance imaging to demonstrate that performance of visual spatial and visual nonspatial working memory tasks involve the same regions of the lateral prefrontal cortex when all factors unrelated to the type of stimulus material are appropriately controlled. These results provide evidence that spatial and nonspatial working memory may not be mediated, respectively, by mid-dorsolateral and mid-ventrolateral regions of the frontal lobe, as widely assumed, and support the alternative notion that specific regions of the lateral prefrontal cortex make identical executive functional contributions to both spatial and nonspatial working memory.

Brain Mapping↗
PubMed1998

A study of performance on tests from the CANTAB battery sensitive to frontal lobe dysfunction in a large sample of normal volunteers: implications for theories of executive functioning and cognitive aging. Cambridge Neuropsychological Test Automated Battery.

Several tests from the CANTAB neuropsychological test battery previously shown to be sensitive to frontal lobe dysfunction were administered to a large group of normal volunteers (N = 341) ranging in age from 21 to 79 years. The main tests included a computerized form of the Tower of London test of planning, a self-ordered spatial working memory task, and a test of attentional set formation and shifting. A computerized form of the Corsi spatial span task was also given. Age-related graded declines in performance were seen, sometimes in a discontinuous manner, especially for the attentional set shifting task (at the extradimensional shift stage). Patterns of deficits reminiscent of frontal lobe or basal ganglia damage were observed in the oldest age group (74-79). However, overall the data were only partially consistent with the hypothesis that frontal lobe functions are the most sensitive to effects of aging. Factor analyses showed that performance in the executive tests was not simply related to a measure of fluid intelligence, and their performance had a factor loading structure distinct from that for the CANTAB tests of visual memory and learning previously administered to the same sample. Finally, only limited support was found for the hypothesis that cognitive aging depends on slowed information processing.

Adult↗
PubMed1998

Abnormal basal ganglia outflow in Parkinson's disease identified with PET. Implications for higher cortical functions.

In this study we examined the effects of striatal dopamine depletion on cortical and subcortical blood flow changes during two tasks known to involve frontostriatal circuitry. Regional cerebral blood flow was measured in six patients with moderate Parkinson's disease and in six age-matched control subjects while they performed easy and difficult versions of a modified Tower of London planning task and a mnemonic variant of this task that required short-term retention and reproduction of problem solutions, as well as a control condition that involved identical visual stimuli and motor responses. Relative to control conditions, the planning task was associated with an increase in cerebral blood flow centred on the internal segment of the right globus pallidus in the age-matched control subjects, and a decrease in the same region in the patients with Parkinson's disease. A similar inverse relationship between the task-specific blood flow change observed in the control group and that observed in the Parkinson's disease patients was not found in any other subcortical or cortical area examined, including regions of the dorsolateral frontal cortex known to be involved in this task. When blood flow in the spatial working memory task was examined, a similarly specific dissociation between the two groups of subjects was observed at similar coordinates in the right pallidum. We conclude that striatal dopamine depletion disrupts the normal pattern of basal ganglia outflow in Parkinson's disease and consequently, affects the expression of frontal-lobe functions by interrupting normal transmission of information through frontostriatal circuitry.

Basal Ganglia↗