Biomedical subjects

C D Frith

Publications and source records attributed to C D Frith.

At least 163 records · Page 9Linked to original sources

PubMed1994

Central nervous pathways mediating angina pectoris.

The central nervous pathways of angina pectoris have never been identified in vivo in man. We used positron emission tomography to examine the changes in regional cerebral blood flow associated with angina pectoris. Dynamic positron emission tomography with 15O-labelled water was used in 12 patients with angina and angiographically proven coronary artery disease to measure regional cerebral blood flow changes during angina induced by intravenous dobutamine. All subjects had typical retrosternal chest pain accompanied by ischaemic electrocardiographic changes during dobutamine infusion. Compared to the resting state, angina was associated with increased regional cerebral blood flow in the hypothalamus (percentage change in regional cerebral blood flow +6.5 and Z score 7.2) periaquaductal grey (+2.6 and 4.0), bilaterally in the thalamus (left: +2.7 and 4.3; right +3.7 and 4.7) and lateral prefrontal cortex (left +11.5 and 7.6; right +8.5 and 7.8) and left inferior anterocaudal cingulate cortex (+9.4 and 6.6). In contrast, it was reduced bilaterally in the mid-rostrocaudal cingulate cortex (left -3.7 and 6.3; right -4.7 and 4.6) and fusiform gyrus (left -3.2 and 4.0; right -3.3 and 3.7), right posterior cingulate (-3.9 and 5.8) and left parietal cortices (-4.8 and 6.3). Several minutes after stopping dobutamine infusion, when the patients no longer experienced angina and the electrocardiographic changes had resolved, thalamic, but not cortical activation could be seen. We propose that the central structures activated constitute the pathways for perception of anginal pain and that the thalamus may act as a gate to afferent pain signals, with cortical activation being necessary for the sensation of pain. This method of investigation may form a basis for research into anomalies of visceral pain perception such as silent myocardial ischaemia.

Adult↗

PubMed1994

Brain regions associated with acquisition and retrieval of verbal episodic memory.

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.

Brain↗

PubMed1994

Identification of the central vestibular projections in man: a positron emission tomography activation study.

The cerebral representation of space depends on the integration of many different sensory inputs. The vestibular system provides one such input and its dysfunction can cause profound spatial disorientation. Using positron emission tomography (PET), we measured regional cerebral perfusion with various vestibular stimulations to map central vestibular projections and to investigate the cerebral basis of spatial disorientation. We showed that the temporoparietal cortex, the insula, the putamen, and the anterior cingulate cortex are the cerebral projections of the vestibular system in man and that the spatial disorientation caused by unilateral vestibular stimulation is associated with their asymmetric activation.

Adult↗

PubMed1994

Central monitoring deficiency and schizophrenic symptoms.

Twenty-five schizophrenic patients currently experiencing Schneiderian symptoms performed a series of tasks in which drawings had to be made in the absence of immediate visual feedback. In comparison to 10 normal controls and to 30 patients not experiencing Schneiderian symptoms, the target group had great difficulty in keeping track of their performance and remembering what actions they had made. These results are consistent with the hypothesis that Schneiderian symptoms (such as delusions of alien control) are associated with impairments in the central monitoring of action.

Adolescent↗

PubMed1994

Imaging transient, randomly occurring neuropsychological events in single subjects with positron emission tomography: an event-related count rate correlational analysis.

Many neuropsychiatric symptom states are idiosyncratic, involuntary, randomly occurring, subjective, and transient. The brain states associated with these clinically important mental states cannot be imaged directly with existing positron emission tomography (PET) techniques. A new PET method that brings such mental/brain states under experimental control for analysis in single subjects is described. It utilizes a slow bolus H2 15O three-dimensional (3D) regional CBF imaging technique. The analysis focuses upon natural or experimentally induced variance in the temporal distribution of specific neuropsychological events over the course of a study session. For each scan, the amount of radioactivity entering the brain during these events is calculated to derive a score reflecting the contribution of the events to the image. A statistical analysis is then performed to identify those pixels in which the intensity covaries with the scan scores over the subject's scans. This permits the identification of the brain areas associated with the mental state of interest. The method is validated using an auditory sentence-monitoring task. The detection in single subjects of cerebral activations associated with recurrent events as brief as 2 s in duration is demonstrated. This method may be used as a means of imaging ephemeral neurologic or neuropsychiatric symptom states or as an alternative to a subtraction design for activation studies.

Adult↗

PubMed1994

The role of the right hemisphere in the interpretation of figurative aspects of language. A positron emission tomography activation study.

We investigated cerebral activity in six normal volunteers using PET to explore the hypothesis that the right hemisphere has a specific role in the interpretation of figurative aspects of language such as metaphors. We also mapped the anatomical structures involved in sentence comprehension. During regional cerebral blood flow measurement subjects were asked to perform three different linguistic tasks: (i) metaphorical comprehension; (ii) literal comprehension of sentences; and (iii) a lexical-decision task. We found that comprehension of sentences compared with the lexical-decision task, induced extensive activation in several regions of the left hemisphere, including the prefrontal and basal frontal cortex, the middle and inferior temporal gyri and temporal pole, the parietal cortex and the precuneus. Comprehension of metaphors was associated with similar activations in the left hemisphere, but in addition, a number of sites were activated in the right hemisphere: the prefrontal cortex, the middle temporal gyrus, the precuneus and the posterior cingulate. We conclude that the interpretation of language involves widespread distributed systems bilaterally with the right hemisphere having a special role in the appreciation of metaphors.

Adult↗

PubMed1994

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

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.

Adult↗

PubMed1994

Clinical correlates of postmortem brain changes in schizophrenia: decreased brain weight and length correlate with indices of early impairment.

From a postmortem study of the brains of 56 patients with schizophrenia and 56 controls, 38 cases whose clinical state had been objectively documented in life were examined to determine whether relations existed between features of the illness and postmortem findings. Decreased brain weight was significantly related (p < 0.05) to poor premorbid global function and to poor academic record, and decreased brain length was related to poorer premorbid global function (p < 0.05) and more severe negative symptoms. These relations are consistent with the view that morphological changes in the brain occur early in the course of the disease--that is, they are in some sense "developmental." An excess of "focal damage" in the patient group relative to controls was unrelated to the presence of morphological change or to features of illness, but was more common in female schizophrenic patients and was also correlated with evidence of cerebrovascular disease. This may possibly be due to a discrepancy between the groups in mode and cause of death.

Brain↗

PubMed1994

Functional anatomy of obsessive-compulsive phenomena.

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.

Adult↗

PubMed1994

Prediction of outcome following a first episode of schizophrenia. A follow-up study of Northwick Park first episode study subjects.

BACKGROUND: Although previous studies have attempted to identify predictors of outcome in schizophrenia, few have prospectively studied first episode patients for an adequate follow-up period. METHOD: The psychopathological predictors of outcome were investigated in a subgroup of 51 subjects, originally included in the Northwick Park study of first episode schizophrenia who were followed up 7.3 years (s.d. 1.1, range 5.3-10.3) after first admission in the Harrow study. Forty-four subjects (24 men, 20 women) were traced. Outcome measures were time to first readmission, occupational level and total duration of hospital admission at five years after first admission. RESULTS: A survival analysis of time to first relapse revealed that the presence of subjective feelings of depression (CATEGO syndrome SD) during the first admission was associated with early relapse while the presence of depressive delusions (CATEGO syndrome DD) and higher educational attainment protected against early relapse. Total duration of hospitalisation at five years after first onset was positively associated with the presence of CATEGO syndromes SD and OD (biological features of depression) and negatively associated with female sex. Poor occupational outcome was not significantly associated with any psychopathological predictors. CONCLUSIONS: Our findings challenge the conventional view that symptoms of depression are associated with better outcome in schizophrenia.

Adolescent↗

PubMed1994

Epilepsy, psychosis, and schizophrenia: clinical and neuropathologic correlations.

This study examines the relationship between epilepsy and psychosis. It compares clinical, EEG, and neuropathologic data from a group of subjects who had both epilepsy and psychosis with similar information from another group of patients who had epilepsy but no evidence of psychotic illness. We examined, blind to clinical diagnosis, gross and microscopic material from whole-brain specimens from 10 patients diagnosed with epilepsy plus schizophrenia-like psychosis, nine subjects diagnosed with epilepsy plus "epileptic psychosis," and 36 individuals with epilepsy (21 from an epileptic colony and 15 from the community at large) who had no history of psychosis (n = 10 + 9 + 21 + 15 = 55). We abstracted case histories without knowledge of pathologic findings. Epileptic colony patients had an earlier age at onset of seizures, while epileptic colony and epileptic psychosis patients had more frequent seizures. Epileptic individuals in the community died at a younger age than did epileptic patients in long-stay hospital care. Psychotic epileptic patients had larger cerebral ventricles, excess periventricular gliosis, and more focal cerebral damage compared with epileptic patients who had no psychotic illness. Epileptic patients with schizophrenia-like psychosis were distinguished from all other groups by a significant excess of pinpoint perivascular white-matter softenings. We found that mesial temporal sclerosis and temporal lobe epilepsy occurred with equal frequency in the psychotic and nonpsychotic groups; generalized seizures occurred more frequently in the psychotic epileptics and the epileptic colony epileptics than in the community epileptic controls.

Aged↗

PubMed1993

Activation of the human hippocampal formation during auditory-verbal long-term memory function.

Clinical data from brain-damaged patients implicates the human hippocampal formation in memory function. We tested the hypothesis that long-term memory function is associated with activation of the hippocampal formation in humans by measuring regional cerebral blood flow changes whilst subjects performed memory tasks. Bilateral hippocampal regional cerebral blood flow was significantly correlated with a measure of the engagement of long-term auditory-verbal memory. No such association was observed for the degree of engagement of auditory-verbal subspan memory. These data provide, for the first time, direct in vivo evidence for the involvement of the hippocampal formation in long-term memory in the intact human brain.

Adult↗

PubMed1993

Principal component analysis learning algorithms: a neurobiological analysis.

The biological relevance of principal component analysis (PCA) learning algorithms is addressed by: (i) describing a plausible biological mechanism which accounts for the changes in synaptic efficacy implicit in Oja's 'Subspace' algorithm (Int. J. neural Syst. 1, 61 (1989)); and (ii) establishing a potential role for PCA-like mechanisms in the development of functional segregation. PCA learning algorithms comprise an associative Hebbian term and a decay term which interact to find the principal patterns of correlations in the inputs shared by a group of units. We propose that the presynaptic component of this decay could be regulated by retrograde signals that are translocated from the terminal arbors of presynaptic neurons to their cell bodies. This proposal is based on reported studies of structural plasticity in the nervous system. By using simulations we demonstrate that PCA-like mechanisms can eliminate afferent connections whose signals are unrelated to the prevalent pattern of afferent activity. This elimination may be instrumental in refining extrinsic cortico-cortical connections that underlie functional segregation.

Algorithms↗

PubMed1993

The neural correlates of the verbal component of working memory.

By repeating words 'in our head', verbal material (such as telephone numbers) can be kept in working memory almost indefinitely. This 'articulatory loop' includes a subvocal rehearsal system and a phonological store. Little is known about neural correlates of this model of verbal short-term memory. We therefore measured regional cerebral blood flow, an index of neuronal activity, in volunteers performing a task engaging both components of the articulatory loop (short-term memory for letters) and a task which engages only the subvocal rehearsal system (rhyming judgement for letters). Stimuli were presented visually and the subjects did not speak. We report here that comparisons of distribution of cerebral blood flow in these conditions localized the phonological store to the left supramarginal gyrus whereas the subvocal rehearsal system was associated with Broca's area. This is, to our knowledge, the first demonstration of the normal anatomy of the components of the 'articulatory loop'.

Brain Mapping↗

PubMed1993

Investigations of the functional anatomy of attention using the Stroop test.

In two separate experiments positron emission tomography (PET) was used to measure changes in regional cerebral blood flow while normal subjects performed the Stroop colour word interference test, a test of selective attention. In the first experiment performance of the Stroop task was associated with activation of right orbito-frontal and bilateral parietal structures, an unexpected result in view of previously reported findings. In addition, there were highly significant time related focal changes in rCBF. A second experiment was therefore carried out which altered the experimental parameters to replicate an earlier study. In this second experiment focal activation of the right anterior cingulate and right frontal polar cortex occurred during the Stroop task. As in the first experiment significant time effects were again apparent. To determine the functionally related brain systems during the performance of the Stroop task a correlation analysis was carried out in relation to blood flow changes induced by experimental manipulation in the right anterior cingulate. This analysis indicated the engagement of a widespread network of anterior brain regions and reciprocal inhibition of posterior brain regions during the performance of the task. The results provide evidence for the involvement of anterior right hemisphere and medial frontal structures in attentional tasks but also indicate that time effects can confound task specific activations. Furthermore subtle experimental treatment parameters, such as stimulus presentation rate, influence the degree and distribution of observed activations.

Adult↗

PubMed1993

The effect of the dopamine agonist, apomorphine, on regional cerebral blood flow in normal volunteers.

Apomorphine, a non-selective dopamine agonist, has been used as a pharmacological probe for investigating central dopaminergic neurotransmission in psychiatric illness. In this study repeated measurements of regional cerebral blood flow (rCBF) were made in normal volunteers before, and after, the administration of apomorphine (5 or 10 micrograms/kg), or placebo. The difference in rCBF, before and after drug (apomorphine versus placebo), was used to identify brain areas affected by apomorphine. Compared to placebo, both doses of apomorphine increased blood flow in the anterior cingulate cortex. Apomorphine 10 micrograms/kg also increased prefrontal rCBF (right > left). No decreases in rCBF were noted following either dose of apomorphine. Apomorphine-induced increases of anterior cingulate blood flow might serve as an in vivo index of central dopamine function. Such an approach would complement established neuroendocrine challenge paradigms for investigating central dopamine neurotransmission in psychiatric illness.

Adult↗

PubMed1993

Functional connectivity: the principal-component analysis of large (PET) data sets.

The distributed brain systems associated with performance of a verbal fluency task were identified in a nondirected correlational analysis of neurophysiological data obtained with positron tomography. This analysis used a recursive principal-component analysis developed specifically for large data sets. This analysis is interpreted in terms of functional connectivity, defined as the temporal correlation of a neurophysiological index measured in different brain areas. The results suggest that the variance in neurophysiological measurements, introduced experimentally, was accounted for by two independent principal components. The first, and considerably larger, highlighted an intentional brain system seen in previous studies of verbal fluency. The second identified a distributed brain system including the anterior cingulate and Wernicke's area that reflected monotonic time effects. We propose that this system has an attentional bias.

Algorithms↗

PubMed1993

Detection of thirty-second cognitive activations in single subjects with positron emission tomography: a new low-dose H2(15)O regional cerebral blood flow three-dimensional imaging technique.

Positron emission tomography regional CBF (rCBF) studies of cognitive processes have traditionally required 30-60 mCi of H2(15)O per scan and intersubject averaging to achieve statistical significance. However, intersubject anatomical, functional, and disease variability can make such an approach problematic. A new method that produces significant results in single subjects is presented. It is based upon high-sensitivity three-dimensional imaging and a "slow" bolus administration of < 15 mCi of H2(15)O per scan. The method is validated in four normal volunteers using control and auditory-language activation tasks with four scans per condition and statistical parametric mapping analysis. It is demonstrated that the rCBF distribution associated with the cognitive state is detected during the arrival of radiotracer in the brain. This occurs over 30 s and constitutes a critical temporal window during which stimulation should be performed. A 90-s acquisition time is found to produce results of greater significance than a 60-s acquisition time. The implications of the results and the functional neuroanatomical findings are discussed. This method is suitable for the study of individual functional neuroanatomy in many neuropsychological, pharmacologic, and symptom states in normal subjects and in patients with psychiatric and neurologic disorders.

Adult↗