Biomedical subjects

C D Frith

Publications and source records attributed to C D Frith.

At least 55 records · Page 3Linked to original sources

PubMed2000

A functional neuroanatomy of tics in Tourette syndrome.

BACKGROUND: Tics are involuntary, brief, stereotyped motor and vocal behaviors often associated with irresistible urges. They are a defining symptom of the classic neuropsychiatric disorder, Tourette syndrome (TS), and constitute an example of disordered human volition. The neural correlates of tics are not well understood and have not been imaged selectively. METHODS: Event-related [(15)O]H(2)O positron emission tomography techniques combined with time-synchronized audio and videotaping were used to determine the duration of, frequency of, and radiotracer input during tics in each of 72 scans from 6 patients with TS. This permitted a voxel-by-voxel correlational analysis within Statistical Parametric Mapping of patterns of neural activity associated with the tics. RESULTS: Brain regions in which activity was significantly correlated with tic occurrence in the group included medial and lateral premotor cortices, anterior cingulate cortex, dorsolateral-rostral prefrontal cortex, inferior parietal cortex, putamen, and caudate, as well as primary motor cortex, the Broca's area, superior temporal gyrus, insula, and claustrum. In an individual patient with prominent coprolalia, such vocal tics were associated with activity in prerolandic and postrolandic language regions, insula, caudate, thalamus, and cerebellum, while activity in sensorimotor cortex was noted with motor tics. CONCLUSIONS: Aberrant activity in the interrelated sensorimotor, language, executive, and paralimbic circuits identified in this study may account for the initiation and execution of diverse motor and vocal behaviors that characterize tics in TS, as well as for the urges that often accompany them. Arch Gen Psychiatry. 2000;57:741-748

Adult↗

PubMed2000

The role of the dorsolateral prefrontal cortex in random number generation: a study with positron emission tomography.

Random number generation (RNG) engages a number of executive processes. We used positron emission tomography (PET) to measure regional cerebral blood flow (rCBF) in six volunteers who performed RNG and a control counting (COUNT) task at six rates paced by a tone. This provided a systematic variation of difficulty of RNG. Relative to COUNT, RNG was associated with significant activation of the left dorsolateral prefrontal cortex (DLPFC), the anterior cingulate, the superior parietal cortex bilaterally, the right inferior frontal cortex, and the left and right cerebellar hemispheres. Faster rates of RNG were associated with a significant decrease in regional cerebral blood flow (rCBF) in the left and right DLPFC and the right superior parietal cortex. rCBF in the left DLPFC was significantly and negatively associated with count score 1, a measure of habitual counting during RNG. These results are discussed in relation to the network modulation model of RNG developed on the basis of our previous studies using transcranial magnetic stimulation and dual task paradigms. This suggests that during RNG, suppression of habitual counting is achieved through the modulatory (inhibitory) influence of the left DLPFC over a number associative network distributed in the superior temporal cortex. At faster rates of RNG the synchronization demands of paced RNG result in the breakdown of this modulatory influence, which is evident from decreased rCBF in the left DLPFC and increased habitual counting at faster rates.

Adult↗

PubMed2000

Reading the mind in cartoons and stories: an fMRI study of 'theory of mind' in verbal and nonverbal tasks.

Previous functional imaging studies have explored the brain regions activated by tasks requiring 'theory of mind'--the attribution of mental states. Tasks used have been primarily verbal, and it has been unclear to what extent different results have reflected different tasks, scanning techniques, or genuinely distinct regions of activation. Here we report results from a functional magnetic resonance imaging study (fMRI) involving two rather different tasks both designed to tap theory of mind. Brain activation during the theory of mind condition of a story task and a cartoon task showed considerable overlap, specifically in the medial prefrontal cortex (paracingulate cortex). These results are discussed in relation to the cognitive mechanisms underpinning our everyday ability to 'mind-read'.

Adult↗

PubMed2000

Recoding, storage, rehearsal and grouping in verbal short-term memory: an fMRI study.

Functional magnetic resonance imaging (fMRI) of healthy volunteers is used to localise the processes involved in verbal short-term memory (VSTM) for sequences of visual stimuli. Specifically, the brain areas underlying (i) recoding, (ii) storage, (iii) rehearsal and (iv) temporal grouping are investigated. Successive subtraction of images obtained from five tasks revealed a network of left-lateralised areas, including posterior temporal regions, supramarginal gyri, Broca's area and dorsolateral premotor cortex. The results are discussed in relation to neuropsychological distinctions between recoding and rehearsal, previous neuroimaging studies of storage and rehearsal, and, in particular, a recent connectionist model of VSTM that makes explicit assumptions about the temporal organisation of rehearsal. The functional modules of this model are tentatively mapped onto the brain in light of the imaging results. Our findings are consistent with the representation of verbal item information in left posterior temporal areas and short-term storage of phonological information in left supramarginal gyrus. They also suggest that left dorsolateral premotor cortex is involved in the maintenance of temporal order, possibly as the location of a timing signal used in the rhythmic organisation of rehearsal, whereas Broca's area supports the articulatory processes required for phonological recoding of visual stimuli.

Adult↗

PubMed2000

Orienting attention in time: behavioural and neuroanatomical distinction between exogenous and endogenous shifts.

Temporal orienting of attention is the ability to focus resources at a particular moment in time in order to optimise behaviour, and is associated with activation of left parietal and premotor cortex [Coull, J. T., Nobre, A. C. Where and when to pay attention: the neural systems for directing attention to spatial locations and to time intervals as revealed by both PET and fMRI. Journal of Neuroscience, 1998, 18, 7426-7435]. In the present experiment, we explored the behavioural and anatomical correlates of temporal orienting to foveal visual stimuli, in order to eliminate any spatial attention confounds. We implemented a two-way factorial design in an event-related fMRI study to examine the factors of trial validity (predictability of target by cue), length of delay (cue-target interval), and their interaction. There were two distinct types of invalid trial: those where attention was automatically drawn to a premature target and those where attention was voluntarily shifted to a delayed time-point. Reaction times for valid trials were shorter than those for invalid trials, demonstrating appropriate allocation of attention to temporal cues. All trial-types activated a shared system, including frontoparietal areas bilaterally, showing that this network is consistently associated with attentional orienting and is not specific to spatial tasks. Distinct brain areas were sensitive to cue-target delays and to trial validity. Long cue-target intervals activated areas involved in motor preparation: supplementary motor cortex, basal ganglia and thalamus. Invalid trials, where temporal expectancies were breached, showed enhanced activation of left parietal and frontal areas, and engagement of orbitofrontal cortex bilaterally. Finally, trial validity interacted with length of delay. Appearance of targets prematurely selectively activated visual extrastriate cortex; while postponement of target appearance selectively activated right prefrontal cortex. These findings suggest that distinct brain areas are involved in redirecting attention based upon sensory events (bottom-up, exogenous shifts) and based upon cognitive expectations (top-down, endogenous shifts).

Adult↗

PubMed2000

Explaining the symptoms of schizophrenia: abnormalities in the awareness of action.

We propose that the primary cognitive deficit associated with delusions of control is a lack of awareness of certain aspects of motor control. This problem arises because of a failure in the mechanism by which the predicted consequences of an action are derived from a forward model based on the intended sequence of motor commands. This problem leads to a number of behavioural consequences, such as a lack of central error correction, many of which have been observed in patients with delusions of control and related symptoms. At the physiological level, delusions of control are associated with over-activity in parietal cortex. We suggest that this over-activity results from a failure to attenuate responses to sensations of limb movements even though these sensations can be anticipated on the basis of the movements intended. The lack of attenuation may arise from long range cortico-cortical disconnections which prevent inhibitory signals arising in the frontal areas which generate motor commands from reaching the appropriate sensory areas.

Awareness↗

PubMed2000

Auditory processing across the sleep-wake cycle: simultaneous EEG and fMRI monitoring in humans.

We combined fMRI and EEG recording to study the neurophysiological responses associated with auditory stimulation across the sleep-wake cycle. We found that presentation of auditory stimuli produces bilateral activation in auditory cortex, thalamus, and caudate during both wakefulness and nonrapid eye movement (NREM) sleep. However, the left parietal and, bilaterally, the prefrontal and cingulate cortices and the thalamus were less activated during NREM sleep compared to wakefulness. These areas may play a role in the further processing of sensory information required to achieve conscious perception during wakefulness. Finally, during NREM sleep, the left amygdala and the left prefrontal cortex were more activated by stimuli having special affective significance than by neutral stimuli. These data suggests that the sleeping brain can process auditory stimuli and detect meaningful events.

Acoustic Stimulation↗

PubMed2000

The perception of self-produced sensory stimuli in patients with auditory hallucinations and passivity experiences: evidence for a breakdown in self-monitoring.

BACKGROUND: To test the hypothesis that certain psychotic symptomatology is due to a defect in self-monitoring, we investigated the ability of groups of psychiatric patients to differentiate perceptually between self-produced and externally produced tactile stimuli. METHODS: Responses to tactile stimulation were assessed in three groups of subjects: schizophrenic patients; patients with bipolar affective disorder or depression; and normal control subjects. Within the psychiatric groups subjects were divided on the basis of the presence or absence of auditory hallucinations and/or passivity experiences. The subjects were asked to rate the perception of a tactile sensation on the palm of their left hand. The tactile stimulation was either self-produced by movement of the subject's right hand or externally produced by the experimenter. RESULTS: Normal control subjects and those psychiatric patients with neither auditory hallucinations nor passivity phenomena experienced self-produced stimuli as less intense, tickly and pleasant than identical, externally produced tactile stimuli. In contrast, psychiatric patients with these symptoms did not show a decrease in their perceptual ratings for tactile stimuli produced by themselves as compared with those produced by the experimenter. This failure to show a difference in perception between self-produced and externally produced stimuli appears to relate to the presence of auditory hallucinations and/or passivity experiences rather than to the diagnosis of schizophrenia. CONCLUSIONS: We propose that auditory hallucinations and passivity experiences are associated with an abnormality in the self-monitoring mechanism that normally allows us to distinguish self-produced from externally produced sensations.

Adult↗

PubMed2000

A cultural effect on brain function.

We present behavioral and anatomical evidence for a multi-component reading system in which different components are differentially weighted depending on culture-specific demands of orthography. Italian orthography is consistent, enabling reliable conversion of graphemes to phonemes to yield correct pronunciation of the word. English orthography is inconsistent, complicating mapping of letters to word sounds. In behavioral studies, Italian students showed faster word and non-word reading than English students. In two PET studies, Italians showed greater activation in left superior temporal regions associated with phoneme processing. In contrast, English readers showed greater activations, particularly for non-words, in left posterior inferior temporal gyrus and anterior inferior frontal gyrus, areas associated with word retrieval during both reading and naming tasks.

Adult↗

PubMed2000

The neural correlates of 'deaf-hearing' in man: conscious sensory awareness enabled by attentional modulation.

Attentional modulation of normal sensory processing has a two-fold impact on human brain activity: activation of a network of localized brain regions is associated with paying attention, and activation of specific sensory regions is enhanced relative to passive stimulation. The mechanisms underlying attentional modulation of perception in patients with lesions of sensory cortices are less well understood. Here we report a unique patient suffering from extensive bilateral destruction of the auditory cortices (including the primary auditory fields) who demonstrated conscious perception of the onset and offset of sounds only when selectively attending to the auditory modality. This is the first description of such an attentively modulated 'deaf-hearing' phenomenon and its neural correlates, using H(2)(15)O-PET. Increases in cerebral blood flow associated with conscious awareness of sound that was achieved by listening attentively (compared with identical auditory stimulation presented when the patient was inattentive) were found bilaterally in the lateral (pre)frontal cortices, the spared middle temporal cortices and the cerebellar hemispheres. We conclude that conscious awareness of sounds may be achieved in the absence of the primary auditory cortex, and that selective, 'top-down' attention, associated with prefrontal systems, exerts a crucial modulatory effect on auditory perception within the remaining auditory system.

Acoustic Stimulation↗

PubMed2000

Dissociable functions in the medial and lateral orbitofrontal cortex: evidence from human neuroimaging studies.

Recent imaging studies show that the orbitofrontal cortex (OFC) is activated during a wide variety of paradigms, including guessing tasks, simple delayed matching tasks and sentence completion. We suggest that, as with other regions of the prefrontal cortex, activity in the OFC is most likely to be observed when there is insufficient information available to determine the appropriate course of action. In these circumstances the OFC, rather than other prefrontal regions, is more likely to be activated when the problem of what to do next is best solved by taking into account the likely reward value of stimuli and responses, rather than their identity or location. We suggest that selection of stimuli on the basis of their familiarity and responses on the basis of a feeling of 'rightness' are also examples of selection on the basis of reward value. Within the OFC, the lateral regions are more likely to be involved when the action selected requires the suppression of previously rewarded responses.

Animals↗

PubMed2000

Functional anatomy of verbal fluency in people with schizophrenia and those at genetic risk. Focal dysfunction and distributed disconnectivity reappraised.

BACKGROUND: PET studies of verbal fluency in schizophrenia report a failure of 'deactivation' of left superior temporal gyrus (STG) in the presence of activation of left dorsolateral prefrontal cortex (DLPFC), which deficit has been attributed to underlying 'functional disconnectivity'. AIM: To test whether these findings provide trait-markers for schizophrenia. METHOD: We used H2(15)O PET to examine verbal fluency in 10 obligate carriers of the predisposition to schizophrenia, 10 stable patients and 10 normal controls. RESULTS: We found no evidence of a failure of left STG deactivation in carriers or patients. Instead, patients failed to deactivate the precuneus relative to other groups. We found no differences in functional connectivity between left DLPFC and left STG but patients exhibited significant disconnectivity between left DLPFC and anterior cingulate cortex. CONCLUSIONS: Failure of left STG 'deactivation' and left fronto-temporal disconnectivity are not consistent findings in schizophrenia; neither are they trait-markers for genetic risk. Prefrontal functional disconnectivity here may characterise the schizophrenic phenotype.

Heterozygote↗

PubMed1999

Inattentional blindness versus inattentional amnesia for fixated but ignored words.

People often are unable to report the content of ignored information, but it is unknown whether this reflects a complete failure to perceive it (inattentional blindness) or merely that it is rapidly forgotten (inattentional amnesia). Here functional imaging is used to address this issue by measuring brain activity for unattended words. When attention is fully engaged with other material, the brain no longer differentiates between meaningful words and random letters, even when they are looked at directly. These results demonstrate true inattentional blindness for words and show that visual recognition wholly depends on attention even for highly familiar and meaningful stimuli at the center of gaze.

Adult↗

PubMed1999

Interacting minds--a biological basis.

The ability to "mentalize," that is to understand and manipulate other people's behavior in terms of their mental states, is a major ingredient in successful social interactions. A rudimentary form of this ability may be seen in great apes, but in humans it is developed to a high level. Specific impairments of mentalizing in both developmental and acquired disorders suggest that this ability depends on a dedicated and circumscribed brain system. Functional imaging studies implicate medial prefrontal cortex and posterior superior temporal sulcus (STS) as components of this system. Clues to the specific function of these components in mentalizing come from single cell recording studies: STS is concerned with representing the actions of others through the detection of biological motion; medial prefrontal regions are concerned with explicit representation of states of the self. These observations suggest that the ability to mentalize has evolved from a system for representing actions.

Animals↗

PubMed1999

Abnormal cingulate modulation of fronto-temporal connectivity in schizophrenia.

Functional neuroimaging provides a novel means of exploring neurophysiological function in schizophrenia. However, most of the studies that have been carried out report their findings in terms of regionally localized abnormalities. In this paper we propose an alternative method of data analysis that emphasizes global integration rather than isolated regional changes in response to psychological tasks. In doing so, we suggest that brain abnormalities in schizophrenia are best characterized as a disturbance in the integration of activity across a number of brain regions. Using a hypothesis-led analysis, we show that the condition is associated with a disruption of the normal anterior cingulate modulation of prefronto-temporal integration. This analytical technique, we suggest, provides a conceptually powerful approach to the imaging of abnormal brain function in psychopathological conditions.

Female↗

PubMed1999

The cerebellum contributes to somatosensory cortical activity during self-produced tactile stimulation.

We used fMRI to examine neural responses when subjects experienced a tactile stimulus that was either self-produced or externally produced. The somatosensory cortex showed increased levels of activity when the stimulus was externally produced. In the cerebellum there was less activity associated with a movement that generated a tactile stimulus than with a movement that did not. This difference suggests that the cerebellum is involved in predicting the specific sensory consequences of movements and providing the signal that is used to attenuate the sensory response to self-generated stimulation. In this paper, we use regression analyses to test this hypothesis explicitly. Specifically, we predicted that activity in the cerebellum contributes to the decrease in somatosensory cortex activity during self-produced tactile stimulation. Evidence in favor of this hypothesis was obtained by demonstrating that activity in the thalamus and primary and secondary somatosensory cortices significantly regressed on activity in the cerebellum when tactile stimuli were self-produced but not when they were externally produced. This supports the proposal that the cerebellum is involved in predicting the sensory consequences of movements. In the present study, this prediction is accurate when tactile stimuli are self-produced relative to when they are externally produced, and is therefore used to attenuate the somatosensory response to the former type of tactile stimulation but not the latter.

Adult↗

PubMed1999

Noradrenergically mediated plasticity in a human attentional neuronal network.

Noradrenaline is implicated in the modulation of attention and arousal, but the neuroanatomical basis of this effect in humans is unknown. A previous functional neuroimaging study failed to find clear effects of clonidine (alpha2 adrenoceptor agonist) on activity of brain regions implicated in attention. Therefore, we now investigate whether clonidine affects the functional integration of a neuroanatomical attentional network, by modulating connectivity between brain regions rather than activity within discrete regions. Following infusion of either clonidine or placebo, positron emission tomography measurements of brain activity were collected in 13 normal subjects while they were either resting or performing an attentional task. Effective connectivity analysis showed that during rest, clonidine decreased the functional strength of connections both from frontal cortex to thalamus and in pathways to and from visual cortex. Conversely, during the attentional task, functional integration generally increased, with changes being centered on parietal cortex (increased connectivity from locus coeruleus to parietal cortex and from parietal cortex to thalamus and frontal cortex). A drug-induced increase in the modulatory effects of frontal cortex on projections from locus coeruleus to parietal cortex was also observed. Collectively, these results highlight cognitively dissociable effects of clonidine on interactions among functionally integrated brain regions and implicate the noradrenergic system in mediating the functional integration of attentional brain systems. The context-sensitive nature of the changes are consistent with observations that noradrenergic drugs have differential effects on brain processes depending on subjects' underlying arousal levels. More generally, the results illustrate the dynamic plasticity of cognitive brain systems following neurochemical challenge.

Adolescent↗

PubMed1999

Dissociating neuromodulatory effects of diazepam on episodic memory encoding and executive function.

RATIONALE: Diazepam and other benzodiazepines impair episodic memory encoding. Deficits in tests of executive function are also reported. In this study, we ask whether the latter effects are secondary to mnemonic impairment, or reflect specific and distinct effects of benzodiazepines on executive function. OBJECTIVES: Using positron emission tomography in healthy human volunteers, we examined similarities in the neuroanatomical correlates of the effect of diazepam on performance of executive compared to episodic memory tasks. Close similarities are proposed to reflect commonalities in the functional effects of the drug. Conversely, any evidence of task-specific regional changes in activity is proposed to reflect distinct functional effects of DZP on the two tasks. METHODS: Twelve volunteers received placebo or 10 mg diazepam in a between-subjects design. During scanning, subjects performed one of four experimental conditions, corresponding to a 2x2 factorial design, with memory encoding and executive function (on-line ordering of stimuli) as the two factors. Drug- or task-induced changes in brain activation indexed the neuroanatomical correlates of each condition. RESULTS: Averaged across all conditions, and compared to placebo, diazepam decreased activity bilaterally in prefrontal and temporal cortices. Within this network of deactivation, left dorsal prefrontal cortex activity was attenuated by diazepam during memory encoding, while left frontal opercular activity was attenuated during ordering. CONCLUSION: This neuroanatomical dissociation reflects distinct functional effects of diazepam on encoding versus ordering tasks. Therefore, the effects of diazepam on ordering tasks are not simply secondary to diazepam effects on episodic memory, but reflect real and distinct effects of the drug on executive function.

Adult↗