Paul W. Burgess

Response suppression, initiation and strategy use following frontal lobe lesions.

Ninety-one patients with cerebral lesions were tested on a task involving two conditions. In the first condition (response initiation) subjects were read a sentence from which the last word was omitted and were required to give a word which completed the sentence reasonably. In the second condition (response suppression) subjects were asked to produce a word unrelated to the sentence. Patients with frontal lobe involvement showed longer response latencies in the first condition and produced more words which were related to the sentence in the second, in comparison to patients with lesions elsewhere. Moreover, in the second condition patients with frontal lobe lesions produced fewer words which showed the use of a strategy during response preparation. Performance on the initiation and suppression conditions was unrelated at the group or single case level. The relationship between response initiation, suppression and strategy use are discussed.

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 Brodmanns 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 ones 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.

Brain regions involved in prospective memory as determined by positron emission tomography.

Prospective memory (PM) refers to the functions that enables a person to carry out an intended act after a delay. Despite the ubiquity of this behaviour, little is known about the supporting brain structures and the roles that they play. In this study, eight healthy participants performed four different PM tasks, each under three conditions: a baseline, and two conditions involving an intention. In the first of the intention conditions, subjects were asked to make a novel response to a certain class of stimuli whilst performing an attention-demanding task. However, the expected stimuli never actually occurred. In the second intention condition subjects were expecting to see these stimuli as before, and they did occur on approximately 20% of trials. Relative to the baseline condition, increases in regional cerebral blood flow (rCBF) as estimated by oxygen-15 positron emission tomography technique across all four tasks were seen in the frontal pole (Brodmanns area 10) bilaterally, right lateral prefrontal and inferior parietal regions plus the precuneus when subjects were expecting a PM stimulus regardless of whether it actually occurred. Further activation was seen in the thalamus when the PM stimuli occurred and was acted upon, with a corresponding rCBF decrease in right lateral prefrontal cortex. It is argued that the first set of region play a role in the maintenance of an intention, with the second set involved additionally in its realisation.

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 Brodmanns 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.

Bizarre responses, rule detection and frontal lobe lesions.

Seventy-seven patients with different cerebral lesions were tested on a rule-detection task where the stimuli were designed in such a way as to minimize the activation of pre-existing schemata. Patients with lesions involving the frontal lobes were poorer at achieving set than patients with lesions elsewhere. In addition, the anteriorly-lesioned group showed a greater tendency to guess and were more likely to abandon a correct rule once it had been attained, but there were no differences between the groups in incidence of perseverative responses. Various plausible explanations of these results are examined, with the most favoured account suggesting that anterior patients show an exaggerated willingness to adopt bizarre hypotheses.

Ecological validity of a simplified version of the Multiple Errands Shopping Test.

Shallice and Burgess (1991) reported the utility of the Multiple Errands Test (MET) in discriminating executive deficits in three frontal lobe patients with preserved high IQ, who were otherwise unimpaired on tests of executive function. The aim of this study was to ascertain the value of a simplified version of the MET (MET-SV) for use with the range of people more routinely encountered in clinical practice. Main findings were as follows: 1) The test discriminated well between neurological patients and controls, and the group effects remained when the difference in current general cognitive functions (WAIS-R FSIQ) was taken into account. 2) The best predictors of performance in the healthy control group (n = 46) were age and the number of times participants asked for help (with more requests associated with poorer performance). 3) In the neurological group, two clear patterns of failure emerged, with performance either characterized by rule breaking or failure to achieve tasks. These two patterns were associated with different dysexecutive symptoms in everyday life. 4) The patients not only made more errors than controls, but also different ones. A scoring method that took this into account markedly increased test sensitivity. 5) Many patients passed traditional tests of executive frontal lobe function but still failed the MET-SV. This pattern was strongly associated with observed dysexecutive symptoms in everyday life. The results demonstrate the clinical utility of the test, and suggest that there are two common and independent sources of failure on multitasking tests in a general neurological population: memory dysfunction, and initiation problems.

Function and localization within rostral prefrontal cortex (area 10)

We propose that rostral prefrontal cortex (PFC; approximating area 10) supports a cognitive system that facilitates either stimulus-oriented (SO) or stimulus-independent (SI) attending. SO attending is the behaviour required to concentrate on current sensory input, whereas SI attending is the mental processing that accompanies self-generated or self-maintained thought. Regions of medial area 10 support processes related to the former, whilst areas of lateral area 10 support processes that enable the latter. Three lines of evidence for this ‘gateway hypothesis’ are presented. First, we demonstrate the predicted patterns of activation in area 10 during the performance of new tests designed to stress the hypothetical function. Second, we demonstrate area 10 activations during the performance of established functions (prospective memory, context memory), which should hypothetically involve the proposed attentional system. Third, we examine predictions about behaviour–activation patterns within rostral PFC that follow from the hypothesis. We show with meta-analysis of neuroimaging investigations that these predictions are supported across a wide variety of tasks, thus establishing a general principle for functional imaging studies of this large brain region. We then show that while the gateway hypothesis accommodates a large range of findings relating to the functional organization of area 10 along a medial–lateral dimension, there are further principles relating to other dimensions and functions. In particular, there is a functional dissociation between the anterior medial area 10, which supports processes required for SO attending, and the caudal medial area 10, which supports processes relating to mentalizing.

A Neural Mechanism Mediating the Impact of Episodic Prospection on Farsighted Decisions

Humans can vividly imagine possible future events. This faculty, episodic prospection, allows the simulation of distant outcomes and desires. Here, we provide evidence for the adaptive function of this capacity and elucidate its neuronal basis. Participants either imagined specific events of spending money (e.g., £35 in 180 days at a pub), or merely estimated what the money could purchase in the scenario. Imagining the future biased subsequent monetary decisions toward choices associated with a higher long-term pay-off. It thus effectively attenuated temporal discounting, i.e., the propensity to devalue rewards with a delay until delivery. Using functional magnetic resonance imaging, we implicate the medial rostral prefrontal cortex (mrPFC) in this effect. Blood oxygen level-dependent signal in this region predicted future-oriented choices on a trial-by-trial basis. Activation reflected the reward magnitude of imagined episodes, and greater reward sensitivity was related to less discounting. This effect was also associated with increased mrPFC–hippocampal coupling. The data suggest that mrPFC uses information conveyed by the hippocampus to represent the undiscounted utility of envisaged events. The immediate experience of the delayed reward value might then bias toward farsighted decisions.

CAN THE NEUROPSYCHOLOGICAL CASE-STUDY APPROACH BE APPLIED TO SCHIZOPHRENIA

Neuropsychological studies of schizophrenia typically apply a small number of tests to a large group of patients. This approach has at least two drawbacks. First, the heterogeneity of the condition will lead to group means which may not reflect the behaviour of any individual. Secondly, it is difficult to infer the nature of the underlying cognitive impairments from a small number of tests, since good performance on a particular test depends on many different cognitive processes. In these circumstances it is more appropriate to apply the methods of cognitive neuropsychology where a large number of tests are used on a single case. This approach has proved fruitful in the study of neurological patients. We have intensively studied 5 chronic schizophrenic patients. These patients varied greatly in terms of overall ability. However, all patients, whatever their overall ability, performed badly on tests sensitive to frontal lobe lesions. This result suggests impairment of the supervisory attentional system in these patients. In addition, one patient suffered from a visual agnosia.

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.