Showing papers by "Raymond J. Dolan published in 1994"

Brain regions associated with acquisition and retrieval of verbal episodic memory

Abstract: It is widely held that conscious recall of past experiences involves a specific system--episodic memory. Patients with amnesia have gross impairments of episodic memory while other kinds of memory remain intact, suggesting that a separable brain system underlies episodic memory. We have used positron emission tomography (PET) to identify components of this system in normal volunteers. A dual-task interference paradigm was used to isolate brain areas associated with acquisition, and a cueing paradigm to isolate the areas concerned with retrieval from verbal episodic memory. Acquisition was associated with activity in the left prefrontal cortex and the retrosplenial area, whereas retrieval was associated with activity in right prefrontal cortex and the precuneus. Our results provide clear evidence that episodic memory involves a network of specific prefrontal and posterior structures which can be fractionated into different component processes.

Functional anatomy of obsessive-compulsive phenomena.

Abstract: Regional cerebral blood flow was measured with H2 15O positron emission tomography in four patients with obsessive-compulsive disorder. Patients were scanned on 12 occasions in the same session, with each scan paired with brief exposure to one of a hierarchy of contaminants that elicited increasingly intense urges to ritualise. The relationship between symptom intensity and regional cerebral blood flow (rCBF; an index of neural activity) was subsequently examined in the group and in individual patients. The group showed significant positive correlations between symptom intensity and blood flow in the right inferior frontal gyrus, caudate nucleus, putamen, globus pallidus and thalamus, and the left hippocampus and posterior cingulate gyrus. Negative correlations were evident in the right superior prefrontal cortex, and the temporoparietal junction, particularly on the right side. The pattern in single subjects was broadly similar, although individual differences in neural response were also observed. A graded relationship between symptom intensity and regional brain activity can thus be identified in obsessive-compulsive disorder. It is hypothesised that the increases in rCBF in the orbitofrontal cortex, neostriatum, global pallidus and thalamus were related to urges to perform compulsive movements, while those in the hippocampus and posterior cingulate cortex corresponded to the anxiety that accompanied them.

A graded task approach to the functional mapping of brain areas implicated in auditory-verbal memory

Abstract: Positron emission tomography measurements of regional cerebral blood flow (rCBF) were performed in normal volunteers during a graded auditory-verbal memory task. Subjects were required to remember and then immediately, and freely, recall a series of auditorily presented word lists varying from two to 13 words in length. Significant regional correlations between rCBF and memory load (word list length) were identified using statistical parametric mapping. Increasing memory load correlated with increasing rCBF in the cerebellar vermis and hemispheres, thalamus bilaterally, the superior and middle frontal gyri bilaterally, anterior insular regions bilaterally, anterior cingulate, precuneus and left and right lateral premotor areas. Increasing memory load also correlated with decreasing rCBF in the left and right superior temporal/insular regions, medial frontal gyrus, Brodmann's area 37 bilaterally, cuneus, inferior parietal lobule bilaterally and the mid-portion of the cingulate cortex. The pattern of rCBF change closely resembled that identified in a previously reported study using a cognitive subtraction paradigm and provides further evidence for a widespread neural system subserving auditory-verbal memory. The patterns of rCBF response suggest that the areas identified are associated with limited capacity processes for encoding and retrieval.

Depression in Parkinson's disease. A positron emission study.

Abstract: BACKGROUND This study investigated biological correlates of depression in patients with idiopathic Parkinson's disease (PD). We tested the hypothesis that in patients with PD and depression, there was regional dysfunction involving brain areas previously implicated in functional imaging studies of patients with primary depression. METHOD Using positron emission tomographic measurements of regional cerebral blood flow (rCBF), patterns of resting rCBF were measured in ten patients with PD and major depression, and ten patients with PD alone. The results were compared with findings from ten patients with primary depression and ten normal controls, scanned using identical methods as part of an earlier study. Groups were matched for age, sex and symptom severity. RESULTS Bilateral decreases in rCBF were observed in anteromedial regions of the medial frontal cortex and the cingulate cortex (Brodmann's areas (BA) 9 and 32) in the depressed PD group, compared with those with PD alone and compared with normal controls. This regional disturbance overlapped that observed in patients with primary depression. CONCLUSIONS The findings indicate that the medial prefrontal cortex is a common area of neural dysfunction in the manifestation of both primary depression and depression in PD.

Neuropsychological dysfunction in depression : the relationship to regional cerebral blood flow

Abstract: The relationship between neuropsychological test performance and regional cerebral blood flow (rCBF) was examined in 29 patients meeting Research Diagnostic Criteria (RDC) for major depression. Following a comprehensive neuropsychological assessment two subsets of tests, comprising tests that discriminated between patients and controls or between patients with varying degrees of global cognitive impairment, were selected. These subtests were entered into a principal components analysis (PCA) which generated a two-factor solution, accounting for 50% of the overall variance in test scores. Individual patient loadings on each of these factors were subsequently correlated with regional cerebral blood flow (rCBF), as measured by positron emission tomography (PET). Both factors demonstrated significant correlations with rCBF in the medial prefrontal cortex and frontal polar cortex while for each factor there were also unique patterns of correlations with posterior brain regions. The findings provide additional evidence that neuropsychological deficits in depression are associated with abnormalities in regional brain function and in particular with the function of the medial prefrontal cortex.

Cognitive function in depression: its relationship to the presence and severity of intellectual decline

Abstract: Cognitive dysfunction is an integral feature of depression, in some cases of sufficient severity to warrant a diagnosis of dementia. There has been little systematic investigation of whether cognitive dysfunction is an inevitable consequence of depression, or is specific to a subgroup of depressed patients. Related to this is the distribution of cognitive dysfunction, whether there is a continuum of impairment or a distinct demented subgroup. Finally, there is the question of which aspects of cognitive function are most sensitive to the intellectual decline seen in depression. A study is described which addresses these issues. The distribution of global cognition was found to be normally distributed in the sample of 29 patients assessed. Based on this distribution and the scores of a control sample, the patients were classified as unimpaired, borderline or impaired. Two sets of independent comparisons were carried out. First, the unimpaired depressed patients were compared to matched non-depressed controls. Significant deficits were found on a range of neuropsychological measures covering aspects of language function, memory, both recall and recognition, attention and behavioural regulation. These same patients were also compared with two groups of matched depressed patients, with varying degrees of global cognitive impairment. In general, the cognitive measures showed a gradient of dysfunction across the three patient groups. Significant differences between the depressed groups were shown on measures of immediate recall, attention and behavioural regulation. The possible significance of attentional factors for the observed memory dysfunction is discussed.

Exploring the functional role of monoaminergic neurotransmission. A method for exploring neurotransmitter dysfunction in psychiatric disorders.

Abstract: Theories of monoaminergic neurotransmitter dys regulation continue to provide the principal framework for the investigation of the pathophysiology of depression and schizophrenia (Losonczy et al, 1987; Willner et al, 1992). The availability of techniques enabling quantitative pharmacological measurements, such as receptor number, to be made in vivo has heightened expectations for an understanding of the mechanisms underlying these conditions. Dopamin ergic receptor systems have been a particular target for in-vivo studies. However, the conflicting results from research based upon these approaches have been a source of disappointment (Wong et al, 1986; Farde et a!, 1990). As little is known concerning the functional role of dopamine in higher brain function in humans, findings based upon quantitative pharmacological measurements are in themselves unlikely to provide a sufficient theoretical basis for a mechanistic understanding of psychiatric disease. A fundamental knowledge of normal brain function is almost certainly a prerequisite for the elaboration of theories of psychiatric disease. Higher brain functions are expressed primarily at a systems level that depend upon an interaction of large populations of neurons organised into complex, often anatomically distributed, systems (Edelman & Mountcastle, 1977). Dynamic interactions between these systems are subject to modifications by a multitude of factors that include neurotransmitter inputs (Edelman, 1987). Therefore a theory of psychiatric illness based upon a putative neuro transmitter dysfunction must address the regulation of neural processes subserving normal psychological functioning. Furthermore, it should explain how neurotransmitter dysregulation leads to the emergence of the psychological symptoms and pathophysiological dysfunctions that characterise psychiatric syndromes. Few, if any, current neurotransmitter theories of psychiatric illness meet these criteria. Undoubtedly, the limiting factor in relation to the monoaminergic-based theories is the paucity of neuroscientific information regarding their regulatory role on cortical function. Findings based upon work in non-human primates have now begun to establish the role of neurotransmitter systems in the regulation of the neural systems subserving specific psychological states (Goldman-Rakic, 1988). An important goal in research on humans is to establish similar links. Novel applications of functional imaging techniques can provide the necessary links by specifying the neuroanatoinical locus of interactions between neural systems subserving specific psychological processes and neurotransmitter inputs (Friston et a!, 199lb). The theoretical basis of such research, with a particular emphasis on dopamine neurotransmission, and an account of preliminary findings from studies in humans, using positron emission tomography (PET), are the basis of this paper.