Biomedical subjects

C D Frith

Publications and source records attributed to C D Frith.

At least 109 records · Page 6Linked to original sources

PubMed1997

Prefrontal dysfunction in depressed patients performing a complex planning task: a study using positron emission tomography.

INTRODUCTION: Patients with unipolar depression show impaired performance on the Tower of London planning task. Positron emission tomography, which has previously identified resting state blood flow abnormalities in depression, was used to investigate neural activity associated with performance of this task in depressed patients and normal controls. METHODS: Six patients with unipolar depression and six matched controls were scanned while performing easy and hard Tower of London problems in a one-touch computerized paradigm and while performing a perceptuomotor control task. RESULTS: The patients in this study showed an expected task-related performance deficit compared with normal subjects. In normal subjects, the task engaged a network of prefrontal cortex, anterior cingulate, posterior cortical areas and subcortical structures including the striatum, thalamus and cerebellum. Depressed patients failed to show significant activation in the cingulate and striatum; activation in the other prefrontal and posterior cortical regions was significantly attenuated relative to controls. Crucially, patients also failed to show the normal augmentation of activation in the caudate nucleus, anterior cingulate and right prefrontal cortex associated with increasing task difficulty. CONCLUSIONS: These findings provide evidence for cingulate, prefrontal and striatal dysfunction associated with impaired task performance in depression. The present results are consistent with a central role of cingulate dysfunction in depression as well as suggesting impaired frontostriatal function.

Adult↗

PubMed1997

Neural mechanisms involved in the processing of global and local aspects of hierarchically organized visual stimuli.

We investigated the functional anatomy involved in sustaining or switching visual attention between different perceptual levels, using functional imaging measures of neural activity. Two experiments were carried out using hierarchically organized letters (i.e. large letters made out of small letters). In a divided-attention task, subjects were required to switch attention between local and global levels. The number of successive stimuli for which subjects had to sustain attention to either the global or local level co-varied significantly with temporal-parietal activations bilaterally. Other activations were also observed in the right orbitofrontal cortex, the right dorsolateral prefrontal cortex, and the right middle temporal gyrus. The number of switches between levels co-varied significantly with activations in the left supplementary motor area and the left medial parietal cortex. In the directed-attention task, subjects were required to attend to either the global or local level of the stimuli throughout all trials; attention to the global aspect resulted in significant activation of the right lingual gyrus while attention to the local aspect significantly activated the left inferior occipital cortex. We suggest that left hemisphere activations with increasing numbers of switches between perceptual levels reflect increased demands on an executive attentional system, while sustained attention to either level activates a predominantly right hemispheric network involving temporal-parietal and dorsolateral prefrontal regions. Overall, the results provide evidence for relative hemispheric specialization for global and local processing in accordance with previous neuropsychological studies. In addition, the findings demonstrate that early visual processing mechanisms in the prestriate cortex are influenced by an attentional system in temporal-parietal areas.

Adult↗

PubMed1997

Space-based and object-based visual attention: shared and specific neural domains.

Visual attention can be primarily allocated to either where an object is in space (with little emphasis on the structure of the object itself) or to the structure of the object (with little emphasis on where in space the object is located). Using PET measures of regional cerebral blood flow (rCBF) to index neural activity, we investigated the shared and specific functional anatomy underlying both of these types of visual attention in a controlled non-cueing non-blocked paradigm that involved identical stimuli across the conditions of interest. The interaction of eye movements with these attentional systems was studied by introducing fixation or free vision as an additional factor. Relative to the control condition, object-based and space-based attention showed significant activations of the left and right medial superior parietal cortex and the left lateral inferior parietal cortex, the left prefrontal cortex and the cerebellar vermis. Significant differential activations were observed during object-based attention in the left striate and prestriate cortex. Space-based attention activated the right prefrontal cortex and the right inferior temporal-occipital cortex. Differential neural activity due to free vision or fixation was observed in occipital areas only. Significant interactions of free vision/fixation on activations due to object-based and space-based attention were observed in the right medial superior parietal cortex and left lateral inferior parietal cortex, respectively. The study provides direct evidence for the importance of the parietal cortex in the control of object-based and space-based visual attention. The results show that object-based and space-based attention share common neural mechanisms in the parietal lobes, in addition to task specific mechanisms in early visual processing areas of temporal and occipital cortices.

Adult↗

PubMed1997

Functional localization of the system for visuospatial attention using positron emission tomography.

PET was used to image the neural system underlying visuospatial attention. Analysis of data at both the group and individual-subject level provided anatomical resolution superior to that described to date. Six right-handed male subjects were selected from a pilot behavioural study in which behavioural responses and eye movements were recorded. The attention tasks involved covert shifts of attention, where peripheral cues indicated the location of subsequent target stimuli to be discriminated. One attention condition emphasized reflexive aspects of spatial orientation, while the other required controlled shifts of attention. PET activations agreed closely with the cortical regions recently proposed to form the core of a neural network for spatial attention. The two attention tasks evoked largely overlapping patterns of neural activation, supporting the existence of a general neural system for visuospatial attention with regional functional specialization. Specifically, neocortical activations were observed in the right anterior cingulate gyrus (Brodmann area 24), in the intraparietal sulcus of right posterior parietal cortex, and in the mesial and lateral premotor cortices (Brodmann area 6).

Attention↗

PubMed1997

Functional brain imaging and the neuropathology of schizophrenia.

We know much more about the anatomy of the frontal lobes than we do about their functions or how these functions go wrong in schizophrenia. Key areas for brain imaging research that will increase our understanding of frontal function concern (1) long-range functional connectivity and the mechanisms by which one brain region modulates activity in another and (2) the mechanisms underlying specific signs and symptoms associated with schizophrenia.

Brain↗

PubMed1997

The neural correlates of the noradrenergic modulation of human attention, arousal and learning.

The prefrontal cortex has been suggested as a site of action for the noradrenergic modulation of cognition. In healthy volunteers attentional deficits can be induced by the alpha 2 adrenoceptor agonist clonidine, without impairment of more explicit tests of frontal lobe function. It is therefore possible that the effects of noradrenaline cannot be localized to a specific brain area such as the prefrontal cortex, but instead involve structures in a more widespread attentional network. A 1.5 micrograms/kg dose of clonidine or placebo was administered to 13 healthy male volunteers performing the rapid visual information processing task, which places demands on both sustained attention and working memory. Twelve positron emission tomography measurements of regional cerebral blood flow (rCBF) were collected during performance of this task and also during a rest state. A second experiment in 12 healthy volunteers examined the effects of a 1.3 micrograms/kg dose of clonidine on the rCBF changes associated with performance of a paired associates learning task compared with passive listening to word pairs. Comparison of each of the experimental tasks with its respective control replicated previous findings. A significant drug x task interaction, common to the two studies, was found in the right thalamus. Inspection of the adjusted rCBF values showed that the effect was due to attenuation of thalamic rCBF during the control states rather than to any effects of clonidine during performance of the cognitive tasks, although the effect was stronger in the rapid visual information processing study than in the paired associates learning study. The significant effect of clonidine during the control as opposed to the "cognitive' activation state is consistent with previous findings in animals and humans demonstrating greater effects of clonidine during states of relatively low arousal. The results suggest neuroanatomical dissociation of the noradrenergic modulation of arousal (via the thalamus) and attention.

Adrenergic Fibers↗

PubMed1997

Anatomy of motor learning. I. Frontal cortex and attention to action.

We used positron emission tomography to study new learning and automatic performance in normal volunteers. Subjects learned sequences of eight finger movements by trial and error. In a previous experiment we showed that the prefrontal cortex was activated during new learning but not during during automatic performance. The aim of the present experiment was to see what areas could be reactivated if the subjects performed the prelearned sequence but were required to pay attention to what they were doing. Scans were carried out under four conditions. In the first the subjects performed a prelearned sequence of eight key presses; this sequence was learned before scanning and was practiced until it had become overlearned, so that the subjects were able to perform it automatically. In the second condition the subjects learned a new sequence during scanning. In a third condition the subjects performed the prelearned sequence, but they were required to attend to what they were doing; they were instructed to think about the next movement. The fourth condition was a baseline condition. As in the earlier study, the dorsal prefrontal cortex and anterior cingulate area 32 were activated during new learning, but not during automatic performance. The left dorsal prefrontal cortex and the right anterior cingulate cortex were reactivated when subjects paid attention to the performance of the prelearned sequence compared with automatic performance of the same task. It is suggested that the critical feature was that the subjects were required to attend to the preparation of their responses. However, the dorsal prefrontal cortex and the anterior cingulate cortex were activated more when the subjects learned a new sequence than they were when subjects simply paid attention to a prelearned sequence. New learning differs from the attention condition in that the subjects generated moves, monitored the outcomes, and remembered the responses that had been successful. All these are nonroutine operations to which the subjects must attend. Further analysis is needed to specify which are the nonroutine operations that require the involvement of the dorsal prefrontal and anterior cingulate cortex.

Adult↗

PubMed1997

Anatomy of motor learning. II. Subcortical structures and learning by trial and error.

We used positron emission tomography to study motor learning by trial and error. Subjects learned sequences of eight finger movements. Tones generated by a computer told the subjects whether any particular move was correct or incorrect. A control condition was used in which the subjects generated moves, but there was no feedback to indicate success or failure, and so on learning occurred. In this condition (free selection) the subjects were required to make a finger movement on each trial and to vary the movements randomly over trials. The subjects had a free choice of which finger to move on any one trial. On this task there was no systematic change in responses over trials and no change in the response times. Two other conditions were included. In one the subjects repetitively moved the same finger on all trials and in a baseline condition the subjects heard the pacing tones and auditory feedback but made no movements. Comparing new learning with the free selection task, there was a small activation in the right prefrontal cortex. This may reflect the fact that in new learning, but not free selection, the subject rehearse past moves and adapt their responses accordingly. The caudate nucleus was strongly activated during new learning. It is suggested that this activity may be related either to mental rehearsal or to reinforcement of the movements as a consequence of the outcomes. The putamen was activated anteriorly on the free selection task and more posteriorly when the subjects repetitively made the same movement. It is suggested that the differences in the location of the peak activation in the striatum may represent the operation of different corticostriatal loops. The cerebellar nuclei (bilaterally) and vermis were more active in the new learning condition than during the performance of the free selection task. There was no difference in the activation of the cerebellum when the free selection task was compared with repetitive performance of the same movement. We tentatively suggest that the basal ganglia may be involved in the specification of movement on the basis of memory of either the movements or the outcomes, but that the cerebellum may be more directly involved in changes in the parameters of movement execution.

Acoustic Stimulation↗

PubMed1996

Learning to find your way: a role for the human hippocampal formation.

The importance of the hippocampal formation of the brain for allocentric spatial mapping of the environment has been suggested by animal lesion and electrophysiological work. Here we describe a positron emission tomography (PET) study designed to investigate the regional cerebral blood flow changes associated with topographical memory formation in humans, i.e. the formation of representations of large-scale environments necessary for way-finding. Topographical learning of an urban environment from viewing of film footage depicting navigation was associated with activation of the right parahippocampal gyrus and hippocampus, with activation also of the left parahippocampal gyrus. In addition, there was activity in the pretuneus. In contrast, the encoding of non-navigation episodic memory in a similar realworld context was not associated with activity in the hippocampal formation. Our results shed light on the neural basis of the human representation of large-scale space pinpointing a particular role for the human hippocampal formation in learning to find one's way.

Adult↗

PubMed1996

Local and distributed effects of apomorphine on fronto-temporal function in acute unmedicated schizophrenia.

We used positron emission tomography (PET) to measure brain activity in healthy control subjects and unmedicated patients with schizophrenia. Subjects were scanned in the context of a combined psychological and pharmacological challenge, and we examined the effects of apomorphine, a drug acting on dopamine receptors, on brain systems engaged by a paced verbal fluency task. This factorial design enabled comparison of control subjects and schizophrenics in terms of the activations engendered by the cognitive task and the pharmacological challenge and the interaction of the two. We report a failure of cognitive task-related activation in anterior cingulate cortex and of task-related deactivation in the left superior temporal gyrus in the schizophrenic subjects. Compared with controls, the impaired cingulate activation was significantly reversed by apomorphine. Additionally, there was a trend for the abnormal fronto-temporal pattern of activation in schizophrenic subjects to be normalized by the drug. Overall, in schizophrenic subjects the effect of apomorphine, which we interpret in terms of a net dopaminergic antagonism, was to modify the brain activity, making the pattern more akin to that seen in control subjects. The results indicate both a regionally specific abnormality of brain function in schizophrenia and an abnormal pattern of fronto-temporal interactions.

Acute Disease↗

PubMed1996

A differential neural response in the human amygdala to fearful and happy facial expressions.

The amygdala is thought to play a crucial role in emotional and social behaviour. Animal studies implicate the amygdala in both fear conditioning and face perception. In humans, lesions of the amygdala can lead to selective deficits in the recognition of fearful facial expressions and impaired fear conditioning, and direct electrical stimulation evokes fearful emotional responses. Here we report direct in vivo evidence of a differential neural response in the human amygdala to facial expressions of fear and happiness. Positron-emission tomography (PET) measures of neural activity were acquired while subjects viewed photographs of fearful or happy faces, varying systematically in emotional intensity. The neuronal response in the left amygdala was significantly greater to fearful as opposed to happy expressions. Furthermore, this response showed a significant interaction with the intensity of emotion (increasing with increasing fearfulness, decreasing with increasing happiness). The findings provide direct evidence that the human amygdala is engaged in processing the emotional salience of faces, with a specificity of response to fearful facial expressions.

Adult↗

PubMed1996

Brain activity during stimulus independent thought.

The neural correlates of stimulus-independent thoughts (SITs) were investigated in two studies of normal volunteers, using positron emission tomography (PET) and H2(15)O to measure regional cerebral blood flow. Subjects rated how frequently SITs occurred while they were concurrently performing different sets of cognitive tasks. In both studies, the main positive correlations between SITs and blood flow were in the medial prefrontal region. These correlations were not attributable to between-task differences in cognitive demand, or to effects of practice on these demands. An association between medial prefrontal activity and SITs is consistent with data linking this region to self-initiated thought, and its activation during tasks which entail thinking which is decoupled from stimuli in the immediate environment.

Adult↗

PubMed1996

Where in the brain does visual attention select the forest and the trees?

The perceptual world is organized hierarchically: the forest consists of trees, which in turn have leaves. Visual attention can emphasize the overall picture (global form) or the focal details of a scene (local components). Neuropsychological studies have indicated that the left hemisphere is biased towards local and the right towards global processing. The underlying attentional and perceptual mechanisms are maximally impaired by unilateral lesions to the temporal and parietal cortex. We measured brain activity of normal subjects during two experiments using 'hierarchically' organized figures. In a directed attention task, early visual processing (prestriate) areas were activated: attention to the global aspect of the figures activated the right lingual gyrus whereas locally directed attention activated the left inferior occipital cortex. In a subsequent divided attention task, the number of target switches from local to global (and vice versa) covaried with temporal-parietal activation. The findings provide direct evidence for hemispheric specialization in global and local perception; furthermore, they indicate that temporal-parietal areas exert attentional control over the neural transformations occurring in prestriate cortex.

Attention↗

PubMed1996

Silent ischemia as a central problem: regional brain activation compared in silent and painful myocardial ischemia.

OBJECTIVE: To test whether the silence of painless myocardial ischemia is caused by abnormal handling by the central nervous system of afferent messages from the heart. DESIGN: Nonrandomized study. SETTING: A tertiary referral center (postgraduate medical school). PATIENTS: 2 matched groups of nondiabetic patients with coronary artery disease. Group A consisted of nine patients with reproducible stress-induced angina; group B consisted of nine patients with reproducible stress-induced myocardial ischemia but no angina. INTERVENTIONS: Intravenous placebo infusion and low-dose (5 and 10 micrograms/ kg per minute) and high-dose (20 to 35 micrograms/kg per minute) dobutamine infusions. MEASUREMENTS: Positron emission tomography was used to measure regional cerebral blood flow changes as an index of neuronal activation during painful and silent myocardial ischemia induced by intravenous dobutamine. RESULTS: Regional cerebral blood flow changes during myocardial ischemia were compared with those during baseline conditions and during placebo infusion. During myocardial ischemia, regional cerebral blood flow increased bilaterally in the thalami and prefrontal, basal frontal, and ventral cingulate corticles in patients in group A. Both thalami were activated in group B, but cortical activation was limited to the right frontal region. A formal comparison of groups A and B showed significant differences (P < 0.01) in activation of the basal frontal cortex, ventral cingulate cortex, and left temporal pole. In both groups, thalamic regional cerebral blood flow remained increased after the symptoms and signs of ischemia had ceased. CONCLUSIONS: Bilateral activation of the thalamus can be shown in both angina and silent ischemia; thus, peripheral nerve dysfunction cannot completely explain silent ischemia. Frontal cortical activation appears to be necessary for the sensation of pain. Abnormal central processing of afferent pain messages from the heart may play a determining role in silent myocardial ischemia.

Afferent Pathways↗

PubMed1996

A multivariate analysis of evoked responses in EEG and MEG data.

This paper presents a multivariate analysis of evoked responses and their spatiotemporal dynamics as measured with electro- or magnetoencephalography. This analysis uses standard techniques (ManCova) to make possible statistical inference about differential responses, after the data have been transformed using singular value decomposition. The generality of this approach is limited only by the assumptions implicit in the general linear model and can range from simple analyses like Hotelling's T2 test (in comparing evoked responses among different conditions) to complex analyses of a multivariate regression type (e.g., characterizing the response components associated with a behavioral or psychophysical parameter). To illustrate the technique we have characterized time-dependent changes (both within and between trials) in magnetic fields, evoked by self-paced movements. Our illustrative analysis showed that movement-evoked components were less prone to adaptation than premovement components, suggesting that functionally distinct (preparatory and early executive) biomagnetic signals show differential adaptation.

Analysis of Variance↗

PubMed1996

Is multivariate analysis of PET data more revealing than the univariate approach? Evidence from a study of episodic memory retrieval.

In a functional imaging study of cued paired associate retrieval, in which the strength of association between pair members was systematically varied, we predicted increased right frontal activity as a function of weakening semantic linkage. An initial univariate analysis found the opposite effect, with greater right frontal activity during recall of strongly linked paired associates. This unexpected result led us to perform a multivariate analysis of covariance (MANCOVA), an approach which proved more informative. This analysis showed that the most significant source of task-related variance was accounted for by a nonlinear relationship not predicted by the prior hypothesis and not revealed by the standard univariate approach. This application of the MANCOVA supports the assertion that multivariate analysis can provide an important adjunct to univariate approaches like statistical parametric mapping (SPM). New perspectives engendered by the MANCOVA still allow for statistical inference but are not constrained by explicit hypotheses about specific task-dependent effects.

Adult↗

PubMed1996

Neural activation during covert processing of positive emotional facial expressions.

Lesion studies indicate distinct neural systems for recognition of facial identity and emotion. Split-brain experiments also suggest that emotional evaluation of a stimulus can occur without conscious identification. The present study tested a hypothesis of a differential neural response, independent of explicit conscious mediation, to emotional compared to nonemotional faces. The experimental paradigm involved holding in mind an image of a face across a 45-s delay while regional cerebral blood flow was measured using positron emission tomography. Prior to the delay, a single face was presented with an explicit instruction to match it to one of two faces, photographed at different angles from the target face, presented at the end of the delay. Repeated blood flow measures were obtained while subjects held happy or neutral faces in mind or during a neutral control fixation condition without initial face presentation. The representation of emotional faces over a delay period, compared to either the nonemotional or the fixation condition, was associated with significant activation in the left ventral prefrontal cortex, the left anterior cingulate cortex, and the right fusiform gyrus. The findings support our hypothesis of a differential neural response to facial emotion, independent of conscious mediation, in regions implicated in the processing of faces and of emotions.

Adult↗

PubMed1996

The role of the thalamus in "top down" modulation of attention to sound.

By correlating rCBF with rate of presentation of tones we used PET to identify brain regions where auditory signals elicited a transient neural response. In one condition volunteers were asked to attend to the tones and ignore visual signals, while in the second condition they were asked to attend to the visual signals and ignore the tones. Activity in primary auditory cortex and adjacent areas was strongly correlated with rate of tone presentation, but this relationship was not affected by the direction of attention. In only one area, the right midthalamus, was the response to tones modulated by attention. In this area responses to tones occurred when attention was directed to sound, but not when attention was directed to visual stimuli. There is considerable evidence that the EEG evoked response to tones (N100/Nd response) is strongly modulated by attention and arises in auditory cortex. The ERP is the sum of activity from many sources. The amplitude of this response reflects not only the amount of activity in these sources, but also the degree of synchrony between them. The difference between these typical ERP results and our result from PET could be resolved if we assume that, in our paradigm, attention did not increase the amount of neural activity in auditory cortex, but rather the degree of synchrony between many sources. The signal in the thalamus, which we observed only when volunteers were attending to the tones, might provide the basis for this synchrony.

Adult↗