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Biomedical subjects

R S Frackowiak

Publications and source records attributed to R S Frackowiak.

At least 19 recordsLinked to original sources
PubMed1992

Measuring the neuromodulatory effects of drugs in man with positron emission tomography.

Cognitive activation in conjunction with pharmacological challenge was used to demonstrate neuromodulation in man. Using positron emission tomography (PET), measurements of regional cerebral blood flow were made during the performance of memory tasks, before and after the administration of apomorphine (dopamine agonist), buspirone (5-HT1A partial agonist) or placebo. Drug effects on memory-induced increases in regional cerebral blood flow were assessed, on a voxel-by-voxel basis, using statistical parametric mapping. Increases of regional cerebral blood flow in response to the memory challenge were attenuated by apomorphine in the dorsolateral prefrontal cortex and augmented in the retrosplenial region of the posterior cingulate. Conversely, buspirone attenuated blood flow increases in the retrosplenial region. These interactions between drugs and a cognitive challenge can best be interpreted as neuromodulatory effects.

Adult↗
PubMed1992

Motor practice and neurophysiological adaptation in the cerebellum: a positron tomography study.

We have used positron tomography (PET) to demonstrate that some parts of the motor system exhibit physiological adaptation during the repeated performance of a simple motor task, but others do not. In contrast to the primary sensori-motor cortex, the cerebellum exhibits a decrease in physiological activation (increases in regional blood flow during performance) with practice. A new application of factorial experimental design to PET activation studies was used to make these measurements in four normal males. This design allowed adaptation to be examined by testing for an interaction between regional cerebral blood flow (rCBF) increases brought about by a motor task and the number of trials (time). These findings are interpreted as the neurophysiological correlates of synaptic changes in the cerebellum associated with motor learning in man.

Adaptation, Physiological↗
PubMed1992

Striatal D2 receptor status in patients with Parkinson's disease, striatonigral degeneration, and progressive supranuclear palsy, measured with 11C-raclopride and positron emission tomography.

Equilibrium striatal: cerebellar 11C-raclopride (RAC) uptake ratios reflect the density of striatal dopamine D2 binding sites. Using positron emission tomographic scanning we have measured striatal RAC uptake in 6 untreated patients with Parkinson's disease (PD), 5 chronically treated patients with PD and a fluctuating response to L-dopa, 10 patients with striatonigral degeneration (SND), and 9 patients with progressive supranuclear palsy (PSP). Regional cerebral blood flow was determined also, with C15O2. Mean striatal: cerebellar RAC uptake was not significantly different from normal in untreated patients with PD, though 2 of these 6 patients showed significantly increased putamen tracer binding. Mean caudate and putamen: cerebellar RAC uptake ratios of the group with PD and a fluctuating response to L-dopa were significantly reduced by 30% and 18%, respectively. The patients with SND had lesser, but significant, 10% and 11% decreases in mean caudate and putamen: cerebellar RAC uptake ratios, respectively, whereas patients with PSP showed 24% and 9% reductions in caudate and putamen: cerebellar RAC binding. Striatal and frontal blood flow were significantly reduced in patients with PSP, but not in patients with PD or SND. In conclusion, striatal D2 binding potential is normal or raised in untreated patients with PD, but reduced in patients with PD and a fluctuating response to L-dopa. Patients with SND and PSP show a decrease in striatal RAC binding, but to a lesser extent than patients with PD and a fluctuating response to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Functional reorganization of the brain in recovery from striatocapsular infarction in man.

We used positron emission tomography (PET) to study organizational changes in the functional anatomy of the brain in 10 patients following recovery from striatocapsular motor strokes. Comparisons of regional cerebral blood flow maps at rest between the patients and 10 normal subjects revealed significantly lower regional cerebral blood flow in the basal ganglia, thalamus, sensorimotor, insular, and dorsolateral prefrontal cortices, in the brainstem, and in the ipsilateral cerebellum in patients, contralateral to the side of the recovered hand. These deficits reflect the distribution of dysfunction caused by the ischemic lesion. Regional cerebral blood flow was significantly increased in the contralateral posterior cingulate and premotor cortices, and in the caudate nucleus ipsilateral to the recovered hand. During the performance of a motor task by the recovered hand, patients activated the contralateral cortical motor areas and ipsilateral cerebellum to the same extent as did normal subjects. However, activation was greater than in normal subjects in both insulae; in the inferior parietal (area 40), prefrontal and anterior cingulate cortices; in the ipsilateral premotor cortex and basal ganglia; and in the contralateral cerebellum. The pattern of cortical activation was also abnormal when the unaffected hand, contralateral to the hemiplegia, performed the task. We showed that bilateral activation of motor pathways and the recruitment of additional sensorimotor areas and of other specific cortical areas are associated with recovery from motor stroke due to striatocapsular infarction. Activation of anterior and posterior cingulate and prefrontal cortices suggests that selective attentional and intentional mechanisms may be important in the recovery process. Our findings suggest that there is considerable scope for functional plasticity in the adult human cerebral cortex.

Adult↗
PubMed1992

Impaired mesial frontal and putamen activation in Parkinson's disease: a positron emission tomography study.

Selection of movement in normal subjects has been shown to involve the premotor, supplementary motor, anterior cingulate, posterior parietal, and dorsolateral prefrontal areas. In Parkinson's disease (PD), the primary pathological change is degeneration of the nigrostriatal dopaminergic projections, and this is associated with difficulty in initiating actions. We wished to investigate the effect of the nigral abnormality in PD on cortical activation during movement. Using C15O2 and positron emission tomography (PET), we studied regional cerebral blood flow in 6 patients with PD and 6 control subjects while they performed motor tasks. Subjects were scanned while at rest, while repeatedly moving a joystick forward, and while freely choosing which of four possible directions to move the joystick. Significant increases in regional cerebral blood flow were determined with covariance analysis. In normal subjects, compared to the rest condition, the free-choice task activated the left primary sensorimotor cortex, left premotor cortex, left putamen, right dorsolateral prefrontal cortex and supplementary motor area, anterior cingulate area, and parietal association areas bilaterally. In the patients with PD, for the free-choice task, compared with the rest condition, there was significant activation in the left sensorimotor and premotor cortices but there was impaired activation of the contralateral putamen, the anterior cingulate, supplementary motor area, and dorsolateral prefrontal cortex. Impaired activation of the medial frontal areas may account for the difficulties PD patients have in initiating movements.

Aged↗
PubMed1992

The identification of presymptomatic parkinsonism: clinical and [18F]dopa positron emission tomography studies in an Irish kindred.

An Irish kindred is described in which 5 of 10 siblings in the fourth or fifth decade of life developed an akinetic-rigid syndrome clinically indistinguishable from idiopathic Lewy body Parkinson's disease. Four of these patients were scanned by positron emission tomography (PET) with [18F]dopa after clinical diagnosis and in all, a profound impairment of tracer uptake into the striatum was recorded. The fifth patient was initially scanned at a time when he was asymptomatic and normal by clinical examination. His scan showed impaired tracer uptake, indicating a subclinical defect in the presynaptic nigrostriatal system. Within months of his scan, he too developed subtle symptoms and signs of parkinsonism although there was little further clinical progression or change in his PET scan over the following year. A clinically normal sibling was also scanned and found to have subclinical impairment of [18F]dopa uptake in the putamen. The 19-year-old daughter of an affected sibling had a mild postural tremor but no other symptoms or signs. The [18F]dopa uptake in her putamen fell at the borderline between normal and parkinsonian values. This study confirms that PET can identify preclinical parkinsonism in at-risk subjects. The finding of abnormalities in several clinically unaffected family members suggests that family studies based on clinical assessment alone may miss a significant number of subclinically affected individuals, leading to an underestimate of any genetic component to Parkinson's disease.

Adult↗
PubMed1992

Impaired activation of the supplementary motor area in Parkinson's disease is reversed when akinesia is treated with apomorphine.

Using positron emission tomography (PET) we previously showed that activation of the putamen, supplementary motor area, and cingulate cortex is impaired in patients with Parkinson's disease (PD) when they are off treatment and perform volitional motor tasks. Evidence suggests that these areas are involved in the generation of internally cued movements in normal subjects. We have now studied the effect of the dopamine agonist apomorphine on cerebral activation when used to treat the akinesia of PD. Regional cerebral blood flow was measured using C15O2 PET in PD patients at rest and when performing paced joystick movements with the right hand in one of four freely chosen directions. All patients used apomorphine regularly, and were studied before treatment, while still "off" but receiving a subcutaneous apomorphine infusion, and when switched "on" with apomorphine. Significant increases in regional cerebral blood flow were determined using statistical parametric mapping. Under resting conditions apomorphine had no effect on focal or global cerebral blood flow. Seven patients with PD performed the motor task adequately in the "off" and "on" states. This group of subjects demonstrated impaired activation of the supplementary motor area and contralateral putamen in the "off" state. Activation of the supplementary motor area significantly improved when the akinesia was reversed with apomorphine. We conclude that the concomitant improvement of supplementary motor area activation and motor function in apomorphine-treated patients with PD provides further evidence for the role of this structure in generating motor programs.

Adult↗
PubMed1992

Langerhans' cell histiocytosis and the nervous system.

We report two cases of Langerhans' cell histiocytosis with unusual central nervous system (CNS) involvement. The first patient had behavioural disturbances, memory loss and diabetes insipidus. His response to a range of treatments was poor. The second patient presented with seizures and headaches suggestive of raised intracranial pressure. Etoposide (VP16) chemotherapy led to a dramatic clinical and radiological improvement. The various CNS manifestations of Langerhans' cell histiocytosis and their management are discussed.

Adult↗
PubMed1992

Effect of the 5-HT1A partial agonist buspirone on regional cerebral blood flow in man.

Repeated measurements of regional cerebral blood flow (rCBF) were made in normal volunteers before, and after, the administration of the 5-HT1A partial agonist, buspirone, or placebo. The difference in rCBF, before and after drug, (buspirone versus placebo) was used to identify brain areas affected by buspirone. Buspirone-induced changes in rCBF were studied under two behavioural conditions (5 word-list learning and 15 word-list learning). Compared to placebo, buspirone increased blood flow in the cuneus during both behavioural states. However, decreases in blood flow, centred in the left dorso-lateral prefrontal cortex and posterior cingulate cortex, were only observed under one of the two behavioural conditions. It is concluded that buspirone-induced alterations in regional cerebral blood flow are better understood, not in relation to the known distribution of monoamine neurotransmitter systems (particularly ascending 5-HT projections), but rather in relation to putative neuronal circuits possibly many synapses "downstream" of buspirone's pharmacological site of action.

Adult↗
PubMed1992

The use of positron emission tomography in the clinical assessment of dementia.

A number of reasons can be cited for performing a test that identifies patients early in their course who have fatal and currently untreatable neurological disorders. At this stage of illness there is clinical ambiguity. The patient, family, and physician are typically faced with a battery of negative test results and an ambiguous clinical impression that can lead to periodic repetition of tests that involve cost, inconvenience, potential morbidity to the patient, and lack of definitive diagnosis. An accurate test would lead to the avoidance of these low-yield, repetitive, and costly evaluations. In addition, such studies can identify homogeneous groups of individuals with degenerative disorders leading to dementia who could be enrolled in experimental therapeutic programs. In these programs therapies could be monitored in an objective and noninvasive fashion using positron emission tomography (PET). The magnitude of the health problems resulting from the dementing illnesses is great in terms of medical practice, economics, and family hardship. The number of individuals with these disorders is predicted to increase dramatically in the future. The ability to provide an accurate diagnosis and more clear prognosis early in the disease course should diminish ambiguity for patients, families, and physicians. Ample evidence is cited in this article to show that PET has the ability to provide such information objectively and noninvasively.

Alzheimer Disease↗
PubMed1992

The anatomy of melancholia--focal abnormalities of cerebral blood flow in major depression.

Using positron emission tomography (PET) and 15Oxygen, regional cerebral blood flow (rCBF) was measured in 33 patients with primary depression, 10 of whom had an associated severe cognitive impairment, and 23 age-matched controls. PET scans from these groups were analysed on a pixel-by-pixel basis and significant differences between the groups were identified on Statistical Parametric Maps (SPMs). In the depressed group as a whole rCBF was decreased in the left anterior cingulate and the left dorsolateral prefrontal cortex (P less than 0.05 Bonferroni-corrected for multiple comparisons). Comparing patients with and without depression-related cognitive impairment, in the impaired group there were significant decreases in rCBF in the left medial frontal gyrus and increased rCBF in the cerebellar vermis (P less than 0.05 Bonferroni-corrected). Therefore an anatomical dissociation has been described between the rCBF profiles associated with depressed mood and depression-related cognitive impairment. The pre-frontal and limbic areas identified in this study constitute a distributed anatomical network that may be functionally abnormal in major depressive disorder.

Adult↗
PubMed1992

The left medial temporal region and schizophrenia. A PET study.

Regional cerebral blood flow (rCBF) was measured in 30 schizophrenic patients with severe, persistent and stable symptoms using positron emission tomography (PET). Directed and non-directed correlational analysis of the relationship between psychopathology and rCBF was used to identify brain structures implicated in three behavioural subsyndromes of schizophrenia. Psychopathology and neurophysiology (rCBF) exhibited high correlations in the left medial temporal region, mesencephalic, thalamic and left striatal structures. The highest correlation was in the left parahippocampal region. A canonical analysis of the same data highlighted the left parahippocampal region and left striatum (globus pallidus) as sites which linked the behavioural subsyndromes in terms of shared rCBF correlates. Increasing severity of psychopathology was associated with increased rCBF in these regions. Disinhibition of left medial temporal lobe activity mediated by fronto-limbic connections is a possible explanation for these findings; however, the prefrontal component appears to be critically dependent on the behavioural subsyndrome.

Adult↗
PubMed1992

Motor recovery after acute ischaemic stroke: a metabolic study.

The metabolic changes occurring after ischaemic stroke were measured to investigate the functional anatomy of clinical motor recovery. Positron emission tomography (PET) and the steady-state 15O technique was used to compare resting relative metabolic distributions at the onset of functional deficit with those following recovery. Ten patients were studied with repeat scans. Motor recovery was associated in some patients with an increase of relative oxygen metabolism in anatomical structures normally involved in motor function in the affected hemisphere, particularly in the cortical motor areas. In those patients without such metabolic changes in the cortex of the diseased hemisphere, relative increases in cortical metabolism in the contralateral hemisphere were associated with better motor recovery than in patients with no relative cortical metabolic increase in either hemisphere. There was no correlation between the degree of improvement in motor function and the severity of motor deficit at onset, the size and site of the lesion and the metabolic changes in the infarcted zone. No particular pattern of global metabolic changes was observed after recovery. Thus different relative patterns of metabolic recovery were seen in patients with different lesions and evidence was found for the participation of contralateral structures in the recovery process in some patients.

Acute Disease↗
PubMed1992

Regional cerebral blood flow abnormalities in depressed patients with cognitive impairment.

Depression with cognitive impairment, so called depressive pseudodementia, is commonly mistaken for a neurodegenerative dementia. Using positron emission tomography (PET) derived measures of regional cerebral blood flow (rCBF) a cohort of 33 patients with major depression was studied. Ten patients displayed significant and reversible cognitive impairment. The patterns of rCBF of these patients were compared with a cohort of equally depressed non-cognitively impaired depressed patients. In the depressed cognitively impaired patients a profile of rCBF abnormalities was identified consisting of decreases in the left anterior medial prefrontal cortex and increases in the cerebellar vermis. These changes were additional to those seen in depression alone and are distinct from those described in neurodegenerative dementia. The cognitive impairment seen in a proportion of depressed patients would seem to be associated with dysfunction of neural systems distinct from those implicated in depression alone or the neurodegenerative dementias.

Bipolar Disorder↗
PubMed1992

Cerebral blood flow and mental processes in schizophrenia.

The patterns of cerebral blood flow associated with three syndromes of schizophrenic symptoms are compared with the loci of cerebral activation in normal subjects during the performance of mental processes implicated in the three syndromes. The psychomotor poverty syndrome, which has been shown to involve a diminished ability to generate words, is associated with decreased perfusion of the dorsolateral prefrontal cortex at a locus which is activated in normal subjects during the internal generation of words. The disorganization syndrome, which has been shown to involve impaired suppression of inappropriate responses (eg in the Stroop test), is associated with increased perfusion of the right anterior cingulate gyrus at a location activated in normal subjects performing the Stroop test. The reality distortion syndrome, which evidence suggests arises from disordered internal monitoring of activity, is associated with increased perfusion in the medial temporal lobe at a locus activated in normal subjects during the internal monitoring of eye movements.

Adult↗