Biomedical subjects

Christopher D Frith

Publications and source records attributed to Christopher D Frith.

18 recordsLinked to original sources

PubMed2006

Differential involvement of regions of rostral prefrontal cortex (Brodmann area 10) in time- and event-based prospective memory.

Rostral prefrontal cortex (approximating Brodmann area 10) has been shown repeatedly to have a role in the maintenance and realization of delayed intentions that are triggered by event cues (i.e., event-based prospective memory). The cerebral organization of the processes associated with the use of time cues (time-based prospective memory) has however received less attention. In two positron emission tomography (PET) studies we therefore examined brain activity associated with time- and event-based prospective memory tasks. In the time-based condition of the first study, young healthy volunteers were asked to make a prospective response based on their self-estimation of the passage of time while engaged in an attention-demanding ongoing activity. In the time-based condition of the second study, participants had a clock available in the ongoing task display and did not need to estimate the time for the prospective response. In the event-based condition of both studies, participants were asked to make a prospective response when prospective cues were presented in ongoing trials. Both studies showed activation differences in rostral prefrontal cortex according to whether the task was time- or event-based. In study one, an area of left superior frontal gyrus was more active in the time-based condition. In study two, three rostral prefrontal regions were more active in the time-based condition: right superior frontal gyrus, anterior medial frontal lobe and anterior cingulate gyrus. A region in left superior frontal gyrus, different from the area found in the first study, was more active in the event-based condition. These results indicate involvement of multiple brain regions of rostral prefrontal cortex in time- and event-based prospective memory. The results are interpreted as reflecting the differing processing demands made by event- or time-based prospective memory tasks, and the differing demands of time-based tasks according to whether a clock is present as an aid.

Adult↗

PubMed2006

The substantia nigra pars compacta and temporal processing.

The basal ganglia and cerebellum are considered to play a role in timing, although their differential roles in timing remain unclear. It has been proposed that the timing of short milliseconds-range intervals involves the cerebellum, whereas longer seconds-range intervals engage the basal ganglia (Ivry, 1996). We tested this hypothesis using positron emission tomography to measure regional cerebral blood flow in eight right-handed males during estimation and reproduction of long and short intervals. Subjects performed three tasks: (1) reproduction of a short 500 ms interval, (2) reproduction of a long 2 s interval, and (3) a control simple reaction time (RT) task. We compared the two time reproduction tasks with the control RT task to investigate activity associated with temporal processing once additional cognitive, motor, or sensory processing was controlled. We found foci in the left substantia nigra and the left lateral premotor cortex to be significantly more activated in the time reproduction tasks than the control RT task. The left caudate nucleus and right cerebellum were more active in the short relative to the long interval, whereas greater activation of the right putamen and right cerebellum occurred in the long rather than the short interval. These results suggest that the basal ganglia and the cerebellum are engaged by reproduction of both long and short intervals but play different roles. The fundamental role of the substantia nigra in temporal processing is discussed in relation to previous animal lesion studies and evidence for the modulating influence of dopamine on temporal processing.

Acoustic Stimulation↗

PubMed2006

Differential functions of lateral and medial rostral prefrontal cortex (area 10) revealed by brain-behavior associations.

We analyzed the behavioral data from 104 neuroimaging studies using positron emission tomography or functional magnetic resonance imaging that reported activation peaks in rostral prefrontal cortex (PFC), approximating Brodmann's area 10. The distribution of absolute x coordinates of activation peaks (i.e., x coordinate regardless of hemisphere) differed significantly from a unimodal normal distribution, reflecting distinct clusters of activation in lateral and medial subregions. These 2 clusters were associated with different patterns of behavioral data. Lateral activations were associated with contrasts between experimental and control conditions where response times (RTs) were slower in the experimental condition. Medial activations were associated with contrasts where RTs were, if anything, faster in experimental than control conditions. These findings place important constraints on theories of rostral PFC functions.

Adult↗

PubMed2006

Performance-related activity in medial rostral prefrontal cortex (area 10) during low-demand tasks.

Neuroimaging studies have frequently observed relatively high activity in medial rostral prefrontal cortex (PFC) during rest or baseline conditions. Some accounts have attributed this high activity to the occurrence of unconstrained stimulus-independent and task-unrelated thought processes during baseline conditions. Here, the authors investigated the alternative possibility that medial rostral PFC supports attention toward the external environment during low-demand conditions. Participants performed a baseline simple reaction time (RT) task, along with 3 other tasks that differed in the requirement to attend to external stimuli versus stimulus-independent thought. Medial rostral PFC activation was observed in the baseline task and in a condition requiring strong engagement with external stimuli, relative to 2 conditions with a greater requirement for stimulus-independent thought. An important finding was that activity in this region was associated with faster RTs in the baseline task, ruling out an explanation in terms of task-unrelated thought processes during this condition. Thus, at least under certain circumstances, medial rostral PFC appears to support attention toward the external environment, facilitating performance in situations that do not require extensive processing of experimental stimuli.

Adult↗

PubMed2006

Functional specialization within rostral prefrontal cortex (area 10): a meta-analysis.

One of the least well understood regions of the human brain is rostral prefrontal cortex, approximating Brodmann's area 10. Here, we investigate the possibility that there are functional subdivisions within this region by conducting a meta-analysis of 104 functional neuroimaging studies (using positron emission tomography/functional magnetic resonance imaging). Studies involving working memory and episodic memory retrieval were disproportionately associated with lateral activations, whereas studies involving mentalizing (i.e., attending to one's own emotions and mental states or those of other agents) were disproportionately associated with medial activations. Functional variation was also observed along a rostral-caudal axis, with studies involving mentalizing yielding relatively caudal activations and studies involving multiple-task coordination yielding relatively rostral activations. A classification algorithm was trained to predict the task, given the coordinates of each activation peak. Performance was well above chance levels (74% for the three most common tasks; 45% across all eight tasks investigated) and generalized to data not included in the training set. These results point to considerable functional segregation within rostral prefrontal cortex.

Algorithms↗

PubMed2005

The effect of adult-acquired hippocampal damage on memory retrieval: an fMRI study.

Bilateral hippocampal pathology typically results in significant memory problems. Despite apparently similar structural damage, patients with such lesions can differ in the pattern of impairment and preservation of memory functions. Previously, an fMRI study of a developmental amnesic patient whose anoxic hippocampal damage was incurred perinatally revealed his residual hippocampal tissue to be active during memory retrieval. This hippocampal activity was apparent during the retrieval of personal and general facts relative to a control task. In this study, we used a similar fMRI paradigm to investigate whether residual hippocampal activation was present also in patient VC with adult-acquired anoxic hippocampal pathology. VC's performance and reaction times on the experimental personal and general fact tasks were comparable to age-matched control subjects. However, in contrast to the elderly control sample and the previous developmental amnesic patient, his residual hippocampal tissue did not show activation changes during the experimental tasks. This finding indicates that patient VC's successful retrieval of personal and general facts was achieved without a significant hippocampal contribution. It further suggests that the hippocampal activation observed in the elderly controls and previous developmental amnesic patient was not necessary for successful task performance. The reason for this difference in hippocampal responsivity between VC and the developmental amnesic patient remains to be determined. We speculate that it may relate to the age at which hippocampal damage occurred reflecting plasticity within the developing brain, or to cognitive differences between VC, the developmental amnesic patient, and the control subjects.

Aged↗

PubMed2005

Blinking suppresses the neural response to unchanging retinal stimulation.

Blinks profoundly interrupt visual input but are rarely noticed, perhaps because of blink suppression, a visual-sensitivity loss that begins immediately prior to blink onset. Blink suppression is thought to result from an extra-retinal signal that is associated with the blink motor command and may act to attenuate the sensory consequences of the motor action. However, the neural mechanisms underlying this phenomenon remain unclear. They are challenging to study because any brain-activity changes resulting from an extra-retinal signal associated with the blink motor command are potentially masked by profound neural-activity changes caused by the retinal-illumination reduction that results from occlusion of the pupil by the eyelid. Here, we distinguished direct top-down effects of blink-associated motor signals on cortical activity from purely mechanical or optical effects of blinking on visual input by combining pupil-independent retinal stimulation with functional MRI (fMRI) in humans. Even though retinal illumination was kept constant during blinks, we found that blinking nevertheless suppressed activity in visual cortex and in areas of parietal and prefrontal cortex previously associated with awareness of environmental change. Our findings demonstrate active top-down modulation of visual processing during blinking, suggesting a possible mechanism by which blinks go unnoticed.

Adult↗

PubMed2005

Involvement of rostral prefrontal cortex in selection between stimulus-oriented and stimulus-independent thought.

We used functional magnetic resonance imaging to investigate brain activity while healthy subjects performed three different tasks, each of which alternated between: (i) phases relying on stimulus-oriented thought (i.e. cognitive processes provoked by incoming sensory information); and (ii) phases relying on stimulus-independent thought (i.e. cognitive processes that were not related to any information in the immediate sensory environment). Within each task, the two phases were matched as closely as possible. In all three tasks, lateral rostral prefrontal cortex was transiently activated by a switch between stimulus-oriented and stimulus-independent thought (regardless of the direction of the switch). Medial rostral prefrontal cortex consistently exhibited sustained activity for stimulus-oriented vs. stimulus-independent thought. These results suggest the involvement of rostral prefrontal cortex in selection between stimulus-oriented and stimulus-independent cognitive processes.

Adult↗

PubMed2004

The brain network associated with acquiring semantic knowledge.

There is ongoing debate about how semantic information is acquired, whether this occurs independently of episodic memory, and what role, if any, brain areas such as hippocampus are required to play. We used auditory stimuli and functional MRI (fMRI) to assess brain activations associated with the incidental acquisition of new and true facts about the world of the sort we are exposed to day to day. A control task was included where subjects heard sentences that described novel scenarios involving unfamiliar people, but these did not convey general knowledge. The incidental encoding task was identical for two stimulus types; both shared the same episodic experience (lying in the brain scanner) and conveyed complex information. Despite this, and considering only those stimuli successfully encoded, compared to a baseline task, a more extensive network of brain regions was found to be associated with exposure to new facts including the hippocampus. Direct comparison between the two stimulus types revealed greater activity in dorsal, ventrolateral and dorsomedial prefrontal cortex, medial dorsal nucleus of the thalamus, and temporal cortex for fact stimuli. The findings suggest that successful encoding is not invariably associated with activation of one particular brain network. Rather, activation patterns may depend on the type of materials being acquired, and the different processes they engender when subjects encode. Qualitatively, from postscan debriefing sessions, it emerged that the factual information was found to be potentially more useful. We suggest that current or prospective utility of incoming information may be one factor that influences the processes engaged during encoding and the concomitant neuronal responses.

Adult↗

PubMed2004

Dissociable neural pathways for the perception and recognition of expressive and instrumental gestures.

Previous functional imaging studies have sought to characterize the neural correlates of gesture representation. However, little is yet known about the representation of different categories of gesture. Here we contrasted the perception of hand gestures that express inner feeling states, e.g. I am angry, I do not care, with the perception of instrumental gestures intended to change the behavior of others by communicating commands, e.g. come here, look over there. We hypothesised that recognition of expressive gestures would activate a network of brain regions associated with mentalising ('theory of mind') whereas instrumental gestures would activate different neural pathways. Twelve normal volunteers underwent fMRI while they watched a series of short videos (3 s duration) of actors performing expressive and instrumental gestures. The volunteers had either to recognise the gesture or to monitor the positions of the hands. As predicted, different neural networks were activated by the observation of instrumental or expressive gestures. The perception of expressive gestures elicited activity in the anterior paracingulate cortex, the amygdala and the temporal poles bilaterally and the right superior temporal sulcus. These regions have all previously been activated during the performance of mentalising tasks. In contrast, instrumental gestures elicited activity in a left-lateralised system previously associated with language and motor imitation.

Adult↗

PubMed2003

Lateral asymmetry in the hippocampal response to the remoteness of autobiographical memories.

The time scale of hippocampal involvement in retrieving memories, particularly those more remote, is still a matter of debate. Some propose that the hippocampus is not involved in the retrieval of remote memories, whereas others assert that it is necessary for memory retrieval in perpetuity. Functional magnetic resonance imaging was used to examine the effect of remoteness on the neural basis of memory. We used a parametric event-related random-effects design in a large group of subjects to overcome some of the limitations of previous neuroimaging studies. We found that the hippocampi were significantly active during the retrieval of autobiographical memories. Notably, the two hippocampi diverged in their responses to remoteness. The right hippocampus showed a temporal gradient, decreasing in activity the more remote the autobiographical memories. No such effect was apparent in the left hippocampus, suggesting its invariant involvement in remembering autobiographical events throughout the lifespan. The dorsal amygdalas showed a temporal gradient similar to the right hippocampus, but emotional valence and intensity were not directly associated with changes in activity. The current results indicate that consideration of lateral asymmetry may help to broaden the scope of theoretical interpretations concerning hippocampal involvement in remote memory.

Acoustic Stimulation↗

PubMed2003

Aging affects the engagement of the hippocampus during autobiographical memory retrieval.

Surprisingly little is known about the neural correlates of remembering real life events in the context of normal aging. We therefore asked young and older adults to retrieve real life autobiographical event memories accrued over decades, while their brains were scanned using functional MRI. There were many commonalities between the groups in the wider network of brain areas active during retrieval. Nevertheless, one key difference emerged; while left hippocampal activation was apparent in the young, bilateral hippocampal activation was evident in older adults and direct comparison between the groups confirmed significantly greater right hippocampal activation in older adults. Notably, this difference was specific to autobiographical event memory retrieval, as the groups were comparable in the areas active during semantic memory retrieval. The present findings show that even when stimuli, tasks and performance appear indistinguishable between young and older adults, neural changes occur in aging with specificity in both the memory type and the brain regions affected. In particular, the results reveal that age-related effects are detectable in the hippocampus. This highlights the need to consider how the dynamic course of normal aging interacts with pathological processes that might also affect the hippocampus. Understanding this relationship may aid prognosis, as well as providing insights into plasticity in the anatomy of memory.

Adult↗

PubMed2003

Development and neurophysiology of mentalizing.

The mentalizing (theory of mind) system of the brain is probably in operation from ca. 18 months of age, allowing implicit attribution of intentions and other mental states. Between the ages of 4 and 6 years explicit mentalizing becomes possible, and from this age children are able to explain the misleading reasons that have given rise to a false belief. Neuroimaging studies of mentalizing have so far only been carried out in adults. They reveal a system with three components consistently activated during both implicit and explicit mentalizing tasks: medial prefrontal cortex (MPFC), temporal poles and posterior superior temporal sulcus (STS). The functions of these components can be elucidated, to some extent, from their role in other tasks used in neuroimaging studies. Thus, the MPFC region is probably the basis of the decoupling mechanism that distinguishes mental state representations from physical state representations; the STS region is probably the basis of the detection of agency, and the temporal poles might be involved in access to social knowledge in the form of scripts. The activation of these components in concert appears to be critical to mentalizing.

Child, Preschool↗

PubMed2003

The role of the rostral frontal cortex (area 10) in prospective memory: a lateral versus medial dissociation.

Using the H(2)(15)O PET method, we investigated whether previous findings of regional cerebral blood flow (rCBF) changes in the polar and superior rostral aspects of the frontal lobes (principally Brodmann's area (BA) 10) during prospective memory (PM) paradigms (i.e. those involving carrying out an intended action after a delay) can be attributed merely to the greater difficulty of such tasks over the baseline conditions typically employed. Three different tasks were administered under four conditions: baseline simple RT; attention-demanding ongoing task only; ongoing task plus a delayed intention (unpracticed); ongoing task plus delayed intention (practiced). Under prospective memory conditions, we found significant rCBF decreases in the superior medial aspects of the rostral prefrontal cortex (BA 10) relative to the baseline or ongoing task only conditions. However more lateral aspects of area 10 (plus the medio-dorsal thalamus) showed the opposite pattern, with rCBF increases in the prospective memory conditions relative to the other conditions. These patterns were broadly replicated over all three tasks. Since both the medial and lateral rostral regions showed: (a) instances where rCBF was lower during a more effortful condition (as estimated by increased RTs and error rates) than in a less effortful one; and (b) there was no correlation between rCBF and RT durations or number of errors in these regions, a simple task difficulty explanation of the rCBF changes in the rostral aspects of the frontal lobes during prospective memory tasks is rejected. Instead, the favoured explanation concentrates upon the particular processing demands made by these situations irrespective of the precise stimuli used or the exact nature of the intention. Moreover, the results suggest different roles for medial and lateral rostral prefrontal cortex, with the former involved in suppressing internally-generated thought, and the latter in maintaining it.

Adult↗

PubMed2003

Distinct neural substrates for visual search amongst spatial versus temporal distractors.

Whether the contribution of the superior parietal cortex (BA7) to attention-demanding tasks is strictly spatial in nature remains unresolved. We used functional magnetic resonance imaging to explore the behavioural and neuroanatomical correlates of non-spatial search for a conjunction of features within a stream of temporally-distracting stimuli. In addition, we compared these data to those from a conventional visuo-spatial search task, performed by the same subjects, in order to determine the specificity of right BA7 activation. Mode of stimulus-distribution (spatial versus temporal) and search type (target defined by a single feature or a conjunction of features) were manipulated in a 2 x 2 factorial design. Behaviourally, the temporal conjunction task was shown to index temporal selective attention. Accuracy of detecting a second target varied with the temporal proximity of two successive targets when subjects searched for a conjunction of features, but not a single feature. The temporal conjunction task activated a network of areas including right superior parietal cortex and bilateral regions of intraparietal sulcus, frontal operculum and putamen. The two latter regions were selectively activated by the attentional demands of the temporal conjunction task when compared directly to the attentional demands of the spatial conjunction task, implicating these regions specifically in selective attention among temporally-distracting stimuli. By comparison, only a very medial region of right BA7 was selectively activated by the spatial conjunction task. The more lateral region of BA7 previously reported by other groups was engaged to a similar degree by both spatial and temporal versions of the conjunction search task.

Adolescent↗

PubMed2003

Autobiographical memory and theory of mind: evidence of a relationship in schizophrenia.

BACKGROUND: It has been proposed that inferences about the mental states of others are drawn after a referral to autobiographical memory. This study explored the relationship between autobiographical memory retrieval and performance on tests of theory of mind in people with schizophrenia. METHOD: Fifty-nine people with a DSM-IV diagnosis of schizophrenia and 44 healthy participants matched for age, sex and estimated IQ were given the Autobiographical Memory Interview (AMI), two measures of theory of mind (ToM) and a logical memory test. RESULTS: There was clear evidence that the people with schizophrenia were under-performing on all tasks. Within the schizophrenia sample, robust relationships existed between the total scores achieved on the AMI and the ToM tasks. Furthermore, there was evidence that the participants with schizophrenia had a tendency to recollect odd or negative events when prompted by the standard questions of the AMI. CONCLUSIONS: The results of this study indicate that when people with schizophrenia attempt to think about the beliefs and intentions of others they use analogical reasoning. Whether this approach is also adopted by other clinical and normal adult groups is a question for future research.

Adult↗

PubMed2002

Reduced frontotemporal functional connectivity in schizophrenia associated with auditory hallucinations.

BACKGROUND: We used functional magnetic resonance imaging (fMRI) to investigate the frontotemporal disconnection hypothesis of schizophrenia. METHODS: Eight DSM-IV schizophrenia patients and 10 control subjects were studied with fMRI while they thought of the missing last word in 128 visually presented sentences. The fMRI data were analyzed comparing the effect of sentence completion (vs. rest) using a random effects analysis. RESULTS: There were no significant group differences in regional brain responses. Correlation coefficients between left temporal cortex (x = -54, y = -42, z = 3) and left dorsolateral prefrontal cortex (x = -39, y = 12, z = 24) were significantly lower in the schizophrenic group and were negatively correlated with the severity of auditory hallucinations. CONCLUSIONS: Previous demonstrations of hypofrontality in schizophrenia may reflect particular task requirements. Frontotemporal functional connectivity is reduced in schizophrenia and may be associated with auditory hallucinations.

Adult↗

PubMed2002

Imaging the intentional stance in a competitive game.

The "intentional stance" is the disposition to treat an entity as a rational agent, possessing particular beliefs, desires, and intentions, in order to interpret and predict it's behavior. The intentional stance is a component of a broader social cognitive function, mentalizing. Here we report a study that investigates the neural substrates of "on-line" mentalizing, using PET, by asking volunteers to second-guess an opponent. In order to identify brain activity specifically associated with adoption of an intentional stance, we used a paradigm that allowed tight control of other cognitive demands. Volunteers played a computerised version of the children's game "stone, paper, scissors." In the mentalizing condition volunteers believed they were playing against the experimenter. In the comparison condition, volunteers believed they were playing against a computer. In fact, during the actual scanning, the "opponent" produced a random sequence in both conditions. The only difference was the attitude, or stance, adopted by the volunteer. Only one region was more active when volunteers adopted the intentional stance. This was in anterior paracingulate cortex (bilaterally). This region has been activated in a number of previous studies involving mentalizing. However, this is the first study suggesting a specific link between activity in this brain region and the adoption of an intentional stance.

Adult↗