Reward-related reversal learning after surgical excisions in orbito-frontal or dorsolateral prefrontal cortex in humans.

Neurophysiological studies in primates and neuroimaging studies in humans suggest that the orbito-frontal cortex is involved in representing the reward value of stimuli and in the rapid learning and relearning of associations between visual stimuli and rewarding or punishing outcomes. In the present study, we tested patients with circumscribed surgical lesions in different regions of the frontal lobe on a new visual discrimination reversal test, which, in an fMRI study (O'Doherty, Kringelbach, Rolls, Hornak, & Andrews, 2001), produced bilateral orbito-frontal cortex activation in normal subjects. In this task, touching one of two simultaneously presented patterns produced reward or loss of imaginary money delivered on a probabilistic basis to minimize the usefulness of verbal strategies. A number of types of feedback were present on the screen. The main result was that the group of patients with bilateral orbito-frontal cortex lesions were severely impaired at the reversal task, in that they accumulated less money. These patients often failed to switch their choice of stimulus after a large loss and often did switch their choice although they had just received a reward. The investigation showed that bilateral lesions were required for this deficit, since patients with unilateral orbito-frontal cortex (or medial prefrontal cortex) lesions were not impaired in the probabilistic reversal task. The task ruled out a simple motor disinhibition as an explanation of the deficit in the bilateral orbito-frontal cortex patients, in that the patients were required to choose one of two stimuli on each trial. A comparison group of patients with dorsolateral prefrontal cortex lesions was in some cases able to do the task, and in other cases, was impaired. Posttest debriefing showed that all the dorsolateral prefrontal patients who were impaired at the task had failed to pay attention to the crucial feedback provided on the screen after each trial about the amount won or lost on each trial. In contrast, all dorsolateral patients who paid attention to this crucial feedback performed normally on the reversal task. Further, it was confirmed that the bilateral orbito-frontal cortex patients had also paid attention to this crucial feedback, but in contrast had still performed poorly at the task. The results thus show that the orbital prefrontal cortex is required bilaterally for monitoring changes in the reward value of stimuli and using this to guide behavior in the task; whereas the dorsolateral prefrontal cortex, if it produces deficits in the task, does so for reasons related to executive functions, such as the control of attention. Thus, the ability to determine which information is relevant when making a choice of pattern can be disrupted by a dorsolateral lesion on either side, whereas the ability to use this information to guide behavior is not disrupted by a unilateral lesion in either the left or the right orbito-frontal cortex, but is severely impaired by a bilateral lesion in this region. Because both abilities are important in many of the tasks and decisions that arise in the course of daily life, the present results are relevant to understanding the difficulties faced by patients after surgical excisions in different frontal brain regions.

Changes in emotion after circumscribed surgical lesions of the orbitofrontal and cingulate cortices.

To analyse the functions of different parts of the prefrontal cortex in emotion, patients with different prefrontal surgical excisions were compared on four measures of emotion: voice and face emotional expression identification, social behaviour, and the subjective experience of emotion. Some patients with bilateral lesions of the orbitofrontal cortex (OFC) had deficits in voice and face expression identification, and the group had impairments in social behaviour and significant changes in their subjective emotional state. Some patients with unilateral damage restricted to the OFC also had deficits in voice expression identification, and the group did not have significant changes in social behaviour or in their subjective emotional state. Patients with unilateral lesions of the antero-ventral part of the anterior cingulate cortex (ACC) and/or medial Brodmann area (BA) 9 were, in some cases, impaired on voice and face expression identification, had some change in social behaviour, and had significant changes in their subjective emotional state. Patients with unilateral lesions of the OFC and of the ACC and/or medial BA 9 were, in some cases, impaired on voice and face expression identification, had some changes in social behaviour, and had significant changes in their subjective emotional state. Patients with dorsolateral prefrontal cortex lesions or with medial lesions outside ACC and medial BA 9 areas (dorsolateral/other medial group) were unimpaired on any of these measures of emotion. In all cases in which voice expression identification was impaired, there were no deficits in control tests of the discrimination of unfamiliar voices and the recognition of environmental sounds. Thus bilateral or unilateral lesions circumscribed surgically within the OFC can impair emotional voice and/or face expression identification, but significant changes in social behaviour and in subjective emotional state are related to bilateral lesions. Importantly, unilateral lesions of the ACC (including some of medial BA 9) can produce voice and/or face expression identification deficits, and marked changes in subjective emotional state. These findings with surgically circumscribed lesions show that within the prefrontal cortex, both the OFC and the ACC/medial BA 9 region are involved in a number of aspects of emotion in humans including emotion identification, social behaviour and subjective emotional state, and that the dorsolateral prefrontal areas are not involved in emotion in these ways.

"Theory of mind" impairments and their relationship to executive functioning following frontal lobe excisions.

It has been suggested that mental states play an important role in determining behaviour and that mental state attributions ("theory of mind") underlie the ability to understand and predict other peoples' behaviour. Theory of mind was investigated in 31 patients with unilateral frontal lobe lesions (15 right-sided and 16 left-sided) by comparing their performance with that of 31 matched control subjects. The ability to infer first- and second-order beliefs was tested by requiring subjects to listen to stories in which a protagonist acted upon a false belief. Both patient groups exhibited significantly impaired performance on the two theory of mind measures. Both frontal lobe groups also exhibited a range of deficits in tests of executive functions, but analyses revealed that these seemed to be independent of theory of mind impairments. These findings are discussed in terms of the hypothesis of a specialized, adaptive brain system underlying theory of mind reasoning ability, and are related to observed difficulties in social functioning among patients with frontal lobe damage.

Dynamic imaging of contrast enhancement in brain tumors.

Gadolinium-DTPA has been shown to be a good probe for demonstrating defects in the blood-brain barrier, but it has a rapid rate of elimination so that peak circulating levels are short-lived. In this study ultrafast echo-planar imaging has been used in combination with a bolus injection of gadolinium-DTPA to evaluate perfusion within brain tumors and to assess the degree of disruption of the blood-brain barrier. The temporal profile of enhancement may allow discrimination between different tumor types.

Visual evoked potentials in the assessment of patients with non-functioning chromophobe adenomas.

The results of visual evoked potential (VEP) examination in 34 patients with histologically confirmed chromophobe adenoma are described and discussed in relation to the clinical, radiological and surgical findings. The VEP is shown to be a reliable method of assessing the function of the intracranial visual pathways which is often more sensitive than conventional methods of examination.

Acute pseudo-obstruction of the colon.

Nineteen patients presenting with pseudo-obstruction of the colon are described. Thirteen were female and the mean age was 65.7 years (48-82). Five cases appeared idiopathic but the remainder were associated with either intercurrent disease, surgery or trauma. Six patients underwent laparotomy, 3 for gross caecal distension and 1 subsequently died with bronchopneumonia. Thirteen patients were treated conservatively with flatus tube decompression or colonoscopy, but 3 died, 1 from a perforated caecum, 1 from a recurrent subarachnoid haemorrhage and 1 from bronchopneumonia. The high mortality of caecal perforation in this condition is stressed, and gross radiological caecal distension with overlying tenderness is an indication for urgent decompression.