Edmund T. Rolls

Psychophysiological and Modulatory Interactions in Neuroimaging

In this paper we introduce the idea of explaining responses, in one cortical area, in terms of an interaction between the influence of another area and some experimental (sensory or task-related) parameter. We refer to these effects as psychophysiological interactions and relate them to interactions based solely on experimental factors (i.e., psychological interactions), in factorial designs, and interactions among neurophysiological measurements (i.e., physiological interactions). We have framed psychophysiological interactions in terms of functional integration by noting that the degree to which the activity in one area can be predicted, on the basis of activity in another, corresponds to the contribution of the second to the first, where this contribution can be related to effective connectivity. A psychophysiological interaction means that the contribution of one area to another changes significantly with the experimental or psychological context. Alternatively these interactions can be thought of as a contribution-dependent change in regional responses to an experimental or psychological factor. In other words the contribution can be thought of as modulating the responses elicited by a particular stimulus or psychological process. The potential importance of this approach lies in (i) conferring a degree of functional specificity on this aspect of effective connectivity and (ii) providing a model of modulation, where the contribution from a distal area can be considered to modulate responses to the psychological or stimulus-specific factor defining the interaction. Although distinct in neurobiological terms, these are equivalent perspectives on the same underlying interaction. We illustrate these points using a functional magnetic resonance imaging study of attention to visual motion and a position emission tomography study of visual priming. We focus on interactions among extrastriate, inferotemporal, and posterior parietal regions during visual processing, under different attentional and perceptual conditions.

The orbitofrontal cortex

The orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odours is represented. The orbitofrontal cortex also receives information about the sight of objects from the temporal lobe cortical visual areas, and is involved in learning and in reversing stimulus-reinforcement associations. The stimulus might be a visual or olfactory stimulus, and the primary (unlearned) reinforcer a taste or touch. Damage to the orbitofrontal cortex impairs the learning and reversal of stimulus-reinforcement associations, and thus the correction of behavioural responses when these are no longer appropriate because previous reinforcement contingencies change. The information which reaches the orbitofrontal cortex for these functions includes information about faces, and damage to the orbitofrontal cortex can impair face expression identification. This evidence thus shows that the orbitofrontal cortex is involved in decoding some primary reinforcers such as taste; in learning and reversing associations of visual and other stimuli to these primary reinforcers; and plays an executive function in controlling and correcting reward-related and punishment-related behaviour, and thus in emotion.

The orbitofrontal cortex: Neuronal activity in the behaving monkey

SummarySingle unit recording of neurons in the orbitofrontal cortex of the alert rhesus monkey was used to investigate responses to sensory stimulation. 32.4% of the neurons had visual responses that had typical latencies of 100–200 ms, and 9.4% responded to gustatory inputs. Most neurons were selective, in that they responded consistently to some stimuli such as foods or aversive objects, but not to others. In a number of cases the neurons responded selectively to particular foods or aversive stimuli. However, this high selectivity could not be explained by simple sensory features of the stimulus, since the responses of some neurons could be readily reversed if the meaning of the stimulus (i.e. whether it was food or aversive) was changed, even though its physical appearance remained identical. Further, some bimodal neurons received convergent visual and gustatory inputs, with matching selectivity for the same stimulus in both modalities, again suggesting that an explanation in terms of simple sensory features is inadequate.Neurons were also studied during the performance of tasks known to be disrupted by orbitofrontal lesions, including a go/no go visual discrimination task and its reversal. 8.6% of neurons had differential responses to the two discriminative stimuli in the task, one of which indicated that reward was available and the other saline. Reversing the meaning of the two stimuli showed that whereas some differential units were closely linked to the sensory features of the stimuli, and some to their behavioural significance, others were conditional, in that they would only respond if a particular stimulus was present, and if it was the one being currently rewarded. Other neurons had activity related to the outcome of the animals response, with some indicating that reinforcement had been received and others, that an error had been made and that a reversal was required.Thus, neurons in the orbitofrontal cortex possess highly coded information about which stimuli are present, as well as information about the consequences of the animals own responses. It is suggested that together they may constitute a neuronal mechanism for determining whether particular visual stimuli continue to be associated with reinforcement, as well as providing for the modification of the animals behavioural responses to such stimuli when those responses are no longer appropriate.

Sensory Specific Satiety in Man

To investigate the specificity of satiety in man, subjects (n=32) rated the pleasantness of the taste of eight foods, were then given one of the foods to eat for lunch, and re-rated the pleasantness of the taste of the eight foods 2 and 20 min after the end of the meal. The pleasantness of the food eaten decreased more than that of the foods not eaten (p<0.001). In a second experiment it was shown that this relative specificity of satiety influenced subsequent food intake. Before a first course, subjects (n=24) rated their liking for the taste of eight foods, were then given one of the foods to eat for lunch, and 2 min after finishing eating re-rated their liking for the taste of the eight foods. Again liking decreased more for the food eaten than for foods not eaten. These changes in liking for the foods eaten and not eaten were highly correlated (p<0.001) with the amounts of those foods eaten in an unexpected second course. Thus in man satiety can be partly specific to foods eaten and this specificity may be an important determinant of the foods selected for consumption.

Face and voice expression identification in patients with emotional and behavioural changes following ventral frontal lobe damage

Impairments in the identification of facial and vocal emotional expression were demonstrated in a group of patients with ventral frontal lobe damage who had socially inappropriate behaviour. The expression identification impairments could occur independently of perceptual impairments in facial recognition, voice discrimination, or environmental sound recognition. The face and voice expression problems did not necessarily occur together in the same patients, providing an indication of separate processing. Poor performance on both expression tests was correlated with the degree of alteration of emotional experience reported by the patients. There was also a strong positive correlation between the degree of altered emotional experience and the severity of the behavioural problems (e.g. disinhibition) found in these patients. A comparison group of patients with brain damage outside the ventral frontal lobe region, without these behavioural problems, was unimpaired on the face expression identification test, was significantly less impaired at vocal expression identification and reported little subjective emotional change. The expression identification deficits in ventral frontal patients may contribute to the abnormal behaviour seen after frontal lesions, and have implications for rehabilitation.

The role of expression and identity in the face-selective responses of neurons in the temporal visual cortex of the monkey

Neurophysiological studies have shown that some neurons in the cortex in the superior temporal sulcus and the inferior temporal gyrus of macaque monkeys respond to faces. To determine if facial factors such as expression and identity are encoded independently by face-responsive neurons, 45 neurons were tested on a stimulus set depicting 3 monkeys with 3 expressions each. As tested on a two-way ANOVA, 15 neurons showed response differences to different identities independently of expression, and 9 neurons showed responses to different expressions independently of identity. Three neurons showed significant effects of both factors. Six of the neurons with responses related to expression responded primarily to calm faces, while 2 responded primarily to threat faces. Of a further set of 31 neurons tested on pairs of different expressions, 6 showed strong responses to open-mouth fear or threat expressions, while 2 showed stronger responses to calm faces than threat expressions. Neurons responsive to expression were found primarily in the cortex in the superior temporal sulcus, while neurons responsive to identity were found primarily in the inferior temporal gyrus. The difference in anatomical distribution was statistically significant. This supports the possibility that specific impairments of the recognition of the identity of a face and of its expression in man are due to damage to or disconnection of separate neuronal substrates.

Representation of Pleasant and Aversive Taste in the Human Brain

In this study, the representation of taste in the orbitofrontal cortex was investigated to determine whether or not a pleasant and an aversive taste have distinct or overlapping representations in this region. The pleasant stimulus used was sweet taste (1 M glucose), and the unpleasant stimulus was salt taste (0.1 M NaCl). We used an ON/OFF block design in a 3T fMRI scanner with a tasteless solution delivered in the OFF period to control for somatosensory or swallowing-related effects. It was found that parts of the orbitofrontal cortex were activated (P < 0.005 corrected) by glucose (in 6/7 subjects) and by salt (in 6/7 subjects). In the group analysis, separate areas of the orbitofrontal cortex were found to be activated by pleasant and aversive tastes. The involvement of the amygdala in the representation of pleasant as well as aversive tastes was also investigated. The amygdala was activated (region of interest analysis, P < 0.025 corrected) by the pleasant taste of glucose (5/7 subjects) as well as by the aversive taste of salt (4/7 subjects). Activation by both stimuli was also found in the frontal opercular/insular (primary) taste cortex. We conclude that the orbitofrontal cortex is involved in processing tastes that have both positive and negative affective valence and that different areas of the orbitofrontal cortex may be activated by pleasant and unpleasant tastes. We also conclude that the amygdala is activated not only by an affectively unpleasant taste, but also by a taste that is affectively pleasant, thus providing evidence that the amygdala is involved in effects produced by positively affective as well as by negatively affective stimuli.

Variety in a meal enhances food intake in man

We find that in man satiety can be partly specific to foods eaten [12]. The possibility that this specificity of satiety leads to overeating if a wide variety of foods is readily available is tested here. The intakes of subjects offered a variety of foods in succession during a meal were compared to intakes when the same food was offered throughout. Subjects (n=36) ate a third more when offered sandwiches with four different fillings than when just one filling was offered (p<0.001). In another study subjects (n=24) ate significantly more when three flavors of yogurt (hazelnut, blackcurrant, orange) which were distinctive in taste, texture and color were offered than when offered just one of the flavors (p<0.01), even if the flavor was the favorite (p<0.01). However, when subjects (n=24) were offered three flavors of yogurt (strawberry, raspberry, cherry) which differed only in taste there was no enhancement of intake when the variety was offered. Having a variety of foods presented in succession during a meal enhances intake, and the more different the foods are the greater the enhancement is likely to be.

The orbitofrontal cortex and beyond: from affect to decision-making.

The orbitofrontal cortex represents the reward or affective value of primary reinforcers including taste, touch, texture, and face expression. It learns to associate other stimuli with these to produce representations of the expected reward value for visual, auditory, and abstract stimuli including monetary reward value. The orbitofrontal cortex thus plays a key role in emotion, by representing the goals for action. The learning process is stimulus-reinforcer association learning. Negative reward prediction error neurons are related to this affective learning. Activations in the orbitofrontal cortex correlate with the subjective emotional experience of affective stimuli, and damage to the orbitofrontal cortex impairs emotion-related learning, emotional behaviour, and subjective affective state. With an origin from beyond the orbitofrontal cortex, top-down attention to affect modulates orbitofrontal cortex representations, and attention to intensity modulates representations in earlier cortical areas of the physical properties of stimuli. Top-down word-level cognitive inputs can bias affective representations in the orbitofrontal cortex, providing a mechanism for cognition to influence emotion. Whereas the orbitofrontal cortex provides a representation of reward or affective value on a continuous scale, areas beyond the orbitofrontal cortex such as the medial prefrontal cortex area 10 are involved in binary decision-making when a choice must be made. For this decision-making, the orbitofrontal cortex provides a representation of each specific reward in a common currency.

Sensory-specific satiety-related olfactory activation of the human orbitofrontal cortex.

When a food is eaten to satiety, its reward value decreases. This decrease is usually greater for the food eaten to satiety than for other foods, an effect termed sensory-specific satiety. In an fMRI investigation it was shown that for a region of the orbitofrontal cortex the activation produced by the odour of the food eaten to satiety decreased, whereas there was no similar decrease for the odour of a food not eaten in the meal. This effect was shown both by a voxel-wise SPM contrast (p <0.05 corrected) and an ANOVA performed on the mean percentage change in BOLD signal in the identified clusters of voxels (p <0.006). These results show that activation of a region of the human orbitofrontal cortex is related to olfactory sensory-specific satiety.