Primate Orbitofrontal Cortex Research Articles

Outcome representations, counterfactual comparisons and the human orbitofrontal cortex: implications for neuroimaging studies of decision-making

Recent research suggests that the primate orbitofrontal cortex (OFC) is critical for representations of outcomes of actions and their subsequent impact on the control of behavior. In parallel, a recent theory of decision-making called decision affect theory (Mellers, Schwartz, and Ritov, Psychological Science, 1997) emphasizes the role of anticipated affective impact of outcomes in guiding choices, and the effects of comparisons with alternative outcomes (i.e., counterfactual effects). In the context of decision affect theory, we present results from two event-related functional MRI experiments consistent with two hypotheses regarding the role of the human OFC in guiding behavior through outcome representation: (1) counterfactual effects are manifested in the human OFC during expectation of outcomes, such that the anticipated affective impact of outcomes is modulated by the nature of the various possible alternative outcomes; (2) a regional specialization exists in the human prefrontal cortex, such that affective impact of potential negative outcomes of actions is represented mainly by the lateral areas of the OFC, while areas situated progressively more medial and dorsal on the ventral and medial PFC are specifically involved in representing the impact of positively valenced outcomes. We also discuss some of the implications that these hypotheses have for neuroimaging studies of reward processing and decision-making, and for studies of neuropsychiatric disorders in which these processes are thought to be disturbed.

Convergence of sensory systems in the orbitofrontal cortex in primates and brain design for emotion.

In primates, stimuli to sensory systems influence motivational and emotional behavior via neural relays to the orbitofrontal cortex. This article reviews studies on the effects of stimuli from multiple sensory modalities on the brain of humans and some other higher primates. The primate 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 odors is represented. A somatosensory input is revealed by neurons that respond to the viscosity of food in the mouth, to the texture (mouth feel) of fat in the mouth, and to the temperature of liquids placed into the mouth. The orbitofrontal cortex also receives information about the sight of objects from the temporal lobe cortical visual areas. Information about each of these modalities is represented separately by different neurons, but in addition, other neurons show convergence between different types of sensory input. This convergence occurs by associative learning between the visual or olfactory input and the taste. In that emotions can be defined as states elicited by reinforcers, the neurons that respond to primary reinforcers (such as taste and touch), as well as learn associations to visual and olfactory stimuli that become secondary reinforcers, provide a basis for understanding the functions of the orbitofrontal cortex in emotion. In complementary neuroimaging studies in humans, it is being found that areas of the orbitofrontal cortex are activated by pleasant touch, by painful touch, by taste, by smell, and by more abstract reinforcers such as winning or losing money. Damage to the orbitofrontal cortex in humans can impair the learning and reversal of stimulus-reinforcement associations and thus the correction of behavioral responses when these are no longer appropriate because previous reinforcement contingencies change. It is striking that humans and other catarrhines, being visual specialists like other anthropoids, interface the visual system to other sensory systems (e.g., taste and smell) in the orbitofrontal cortex.

Long- and short-range reward expectancy in the primate orbitofrontal cortex.

The orbitofrontal cortex (OFC) is important in motivation and emotion. We previously reported reward expectancy-related delay activities during a delayed reaction time task in primate OFC neurons. To further investigate the significance of the OFC in motivational operations, we examined pre-instruction, baseline activities of OFC neurons in relation to reward expectancy during the delayed reaction time task. In this task, an instruction cue indicated whether reward would be present or absent in the trial. Each set of four consecutive trials constituted one block within which three different kinds of rewards and one trial with no reward were given in a fixed order that differed from the monkey's reward preference. We identified two types of OFC neurons with reward expectancy-related pre-instruction activities: Step-type neurons showed stepwise changes (increase or decrease) in pre-instruction activity toward the trial with a particular outcome, which usually was the most or least attractive within a block; Pref-type neurons showed pre-instruction activity changes according to the monkey's preference for each trial's outcome. We propose that Step-type and Pref-type neurons are related to long-range and short-range reward expectancies of a particular outcome, respectively. The OFC is considered to play important roles in goal-directed behaviour by adjusting the motivational level toward a certain (current or future) outcome of a particular motivational significance based on the two kinds of reward expectancy processes. Impairments in goal-directed behaviour by OFC patients may be caused by a lack of long-range expectancy or by a deficit in compromising between short-range and long-range expectancies.

Orbitofrontal cortex: neuronal representation of oral temperature and capsaicin in addition to taste and texture

The primate orbitofrontal cortex is a site of convergence of information from primary taste, olfactory and somatosensory cortical areas. We describe the discovery of a population of single neurons in the macaque orbitofrontal cortex that responds to the temperature of a liquid in the mouth. The temperature stimuli consisted of water at 10 °C, 23 °C, 37 °C and 42 °C. Twenty-six of the 1149 neurons analyzed (2.3%) responded to oral temperature. The tuning profiles of the neurons to temperature showed that some of the neurons had graded responses to increasing temperature (27%), others responded to cold (10 °C) stimuli (27%), and others were tuned to temperature (46%). The neuronal responses were also measured to taste stimuli, viscosity stimuli (carboxymethyl-cellulose in the range 1–10,000 cP), and capsaicin (10 μM). Of 70 neurons with responses to any of these stimuli, 7.1% were unimodal temperature; 11.3% were temperature and taste-sensitive; 7.1% were temperature and viscosity-sensitive; and 11.3% were temperature, taste and viscosity sensitive. Capsaicin activated 15.7% of the population of responsive neurons tested. These results provide the first evidence of how the temperature of what is in the mouth is represented at the neuronal level in the orbitofrontal cortex and the first evidence for any primate cortical area that in some cases this information converges onto single neurons with inputs produced by other sensory properties of food, including taste and texture. The results provide a basis for understanding how particular combinations of oral temperature, taste, and texture can influence the palatability of foods.

Representations of the texture of food in the primate orbitofrontal cortex: neurons responding to viscosity, grittiness, and capsaicin.

The primate orbitofrontal cortex (OFC) is a site of convergence from taste, olfactory, and somatosensory cortical areas. We describe a population of single neurons in the macaque OFC that responds to the texture of food in the mouth. Use of oral viscosity stimuli consisting of carboxymethylcellulose (CMC) in the range 1-10,000 centipoise showed that the responses of one subset of these neurons were related to stimulus viscosity. Some of the neurons had increasing responses to increasing viscosity, some had decreasing responses, and some neurons were tuned to a range of viscosities. These neurons are a different population to oral fat-sensitive neurons, in that their responses to fats (e.g., safflower oil), to silicone oil [(Si(CH3)2O)n], and to mineral oil (hydrocarbon) depended on the viscosity of these oils. Thus there is a dissociation between texture channels used to sense viscosity and fat. Some of these viscosity-sensitive single neurons were unimodal (somatosensory; 25%) and some received convergent taste inputs (75%). A second subpopulation of neurons responded to gritty texture (produced by microspheres suspended in CMC). A third subpopulation of neurons responded to capsaicin. These results provide evidence about the information channels used to represent the texture and flavor of food in a part of the brain important in appetitive responses to food and are relevant to understanding the physiological and pathophysiological processes related to food intake, food selection, and the effects of variety of food texture in combination with taste and other inputs that affect food intake.

Neurons in the primate orbitofrontal cortex respond to fat texture independently of viscosity.

The primate orbitofrontal cortex (OFC) is a site of convergence from primary taste, olfactory, and somatosensory cortical areas. We describe the responses of a population of single neurons in the OFC that respond to orally applied fat (e.g., safflower oil) and to substances with a similar texture but different chemical composition, such as mineral oil (hydrocarbon) and silicone oil [(Si(CH3)2O)n]. These findings provide evidence that the neurons respond to the oral texture of fat, sensed by the somatosensory system. Use of an oral viscosity stimulus consisting of carboxymethyl-cellulose in the range 1-10,000 centipoise (cP) showed that the responses of these fat-sensitive neurons are not related to stimulus viscosity. Thus a textural component independent of viscosity and related to the slick or oily property is being used to activate these oral fat-sensitive neurons. Moreover, a separate population of neurons responds to viscosity (produced, e.g., by the carboxymethyl-cellulose series), but not to fat with the same viscosity. Thus there is a dissociation between texture channels used to sense fat viscosity and non-fat-produced viscosity. Further, free fatty acids such as linoleic acid do not activate these neurons, providing further evidence that the oral fat-sensing mechanism through which these OFC neurons are activated is not gustatory but textural. Most of this population of fat-sensitive neurons receive convergent taste inputs. These results provide evidence about how oral fat is sensed and are relevant to understanding the physiological and pathophysiological processes related to fat intake.

The representation of umami taste in the human and macaque cortex

To investigate the neural encoding of glutamate (umami) taste in the primate, recordings were made from taste responsive neurons in the cortical taste areas in macaques. Most of the neurons were in the orbitofrontal cortex (secondary) taste area. First, it was shown that there is a representation of the taste of glutamate which is separate from the representation of the other prototypical tastants sweet (glucose), salt (NaCl), bitter (quinine) and sour (HCl). Second, it was shown that single neurons that had their best responses to sodium glutamate also had good responses to glutamic acid. Third, it was shown that the responses of these neurons to the nucleotide umami tastant inosine 5′-monophosphate were more correlated with their responses to monosodium glutamate than to any prototypical tastant. Fourth, concentration-response curves showed that concentrations of monosodium glutamate as low as 0.001 M were just above threshold for some of these neurons. Fifth, some neurons in the orbitofrontal region, which responded to monosodium glutamate and other food tastes, decreased their responses after feeding with monosodium glutamate to behavioural satiety, revealing a mechanism of satiety. In some cases this reduction was sensory-specific. Sixth, it was shown in psychophysical experiments in humans that the flavor of umami is strongest with a combination of corresponding taste and olfactory stimuli (e.g. monosodium glutamate and garlic odor). The hypothesis is proposed that part of the way in which glutamate works as a flavor enhancer is by acting in combination with corresponding food odors. The appropriate associations between the odor and the glutamate taste may be learned at least in part by olfactory to taste association learning in the primate orbitofrontal cortex. Seventh, in neuroimaging experiments with functional magnetic resonance imaging (fMRI) in humans, it was shown that in humans umami taste produced by monosodium glutamate or by inosine monophosphate produced activation in a region of the anterior insula which is the putative human primary taste cortex and in a part of the orbitofrontal cortex which is the putative human secondary taste cortex.

The rules of formation of the olfactory representations found in the orbitofrontal cortex olfactory areas in primates.

Approximately 35% of neurons in the orbitofrontal cortex taste and olfactory areas with olfactory responses provide a representation of odour that depends on the taste with which the odour has been associated previously. This representation is produced by a slowly acting learning mechanism that learns associations between odour and taste. Other neurons in the orbitofrontal cortex respond to both the odour and to the mouth feel of fat. The representation of odour thus moves for at least some neurons in the orbitofrontal cortex beyond the domain of physico-chemical properties of the odours to a domain where the ingestion-related significance of the odour determines the representation provided. Olfactory neurons in the primate orbitofrontal cortex decrease their responses to a food eaten to satiety, but remain responsive to other foods, thus contributing to a mechanism for olfactory sensory-specific satiety. It has been shown in neuroimaging studies that the human orbitofrontal cortex provides a representation of the pleasantness of odour, in that the activation produced by the odour of a food eaten to satiety decreases relative to another food-related odour not eaten in the meal. In the same general area there is a representation of the pleasantness of the smell, taste and texture of a whole food, in that activation in this area decreases to a food eaten to satiety, but not to a food that has not been eaten in the meal.

Reward-related neuronal activity during go-nogo task performance in primate orbitofrontal cortex.

The orbitofrontal cortex appears to be involved in the control of voluntary, goal-directed behavior by motivational outcomes. This study investigated how orbitofrontal neurons process information about rewards in a task that depends on intact orbitofrontal functions. In a delayed go-nogo task, animals executed or withheld a reaching movement and obtained liquid or a conditioned sound as reinforcement. An initial instruction picture indicated the behavioral reaction to be performed (movement vs. nonmovement) and the reinforcer to be obtained (liquid vs. sound) after a subsequent trigger stimulus. We found task-related activations in 188 of 505 neurons in rostral orbitofrontal area 13, entire area 11, and lateral area 14. The principal task-related activations consisted of responses to instructions, activations preceding reinforcers, or responses to reinforcers. Most activations reflected the reinforcing event rather than other task components. Instruction responses occurred either in liquid- or sound-reinforced trials but rarely distinguished between movement and nonmovement reactions. These instruction responses reflected the predicted motivational outcome rather than the behavioral reaction necessary for obtaining that outcome. Activations preceding the reinforcer began slowly and terminated immediately after the reinforcer, even when the reinforcer occurred earlier or later than usually. These activations preceded usually the liquid reward but rarely the conditioned auditory reinforcer. The activations also preceded expected drops of liquid delivered outside the task, suggesting a primary appetitive rather than a task-reinforcing relationship that apparently was related to the expectation of reward. Responses after the reinforcer occurred in liquid- but rarely in sound-reinforced trials. Reward-preceding activations and reward responses were unrelated temporally to licking movements. Several neurons showed reward responses outside the task but instruction responses during the task, indicating a response transfer from primary reward to the reward-predicting instruction, possibly reflecting the temporal unpredictability of reward. In conclusion, orbitofrontal neurons report stimuli associated with reinforcers are concerned with the expectation of reward and detect reward delivery at trial end. These activities may contribute to the processing of reward information for the motivational control of goal-directed behavior.

Modifications of reward expectation-related neuronal activity during learning in primate orbitofrontal cortex.

This study investigated how neuronal activity in orbitofrontal cortex related to the expectation of reward changed while monkeys repeatedly learned to associate new instruction pictures with known behavioral reactions and reinforcers. In a delayed go-nogo task with several trial types, an initial picture instructed the animal to execute or withhold a reaching movement and to expect a liquid reward or a conditioned auditory reinforcer. When novel instruction pictures were presented, animals learned according to a trial-and-error strategy. After experience with a large number of novel pictures, learning occurred in a few trials, and correct performance usually exceeded 70% in the first 60-90 trials. About 150 task-related neurons in orbitofrontal cortex were studied in both familiar and learning conditions and showed two major forms of changes during learning. Quantitative changes of responses to the initial instruction were seen as appearance of new responses, increase of existing responses, or decrease or complete disappearance of responses. The changes usually outlasted initial learning trials and persisted during subsequent consolidation. They often modified the trial selectivities of activations. Increases might reflect the increased attention during learning and induce neuronal changes underlying the behavioral adaptations. Decreases might be related to the unreliable reward-predicting value of frequently changing learning instructions. The second form of changes reflected the adaptation of reward expectations during learning. In initial learning trials, animals reacted as if they expected liquid reward in every trial type, although only two of the three trial types were rewarded with liquid. In close correspondence, neuronal activations related to the expectation of reward occurred initially in every trial type. The behavioral indices for reward expectation and their neuronal correlates adapted in parallel during the course of learning and became restricted to rewarded trials. In conclusion, these data support the notion that neurons in orbitofrontal cortex code reward information in a flexible and adaptive manner during behavioral changes after novel stimuli.

The Representation of Umami Taste in the Taste Cortex

To investigate the neural encoding of glutamate (umami) taste in the primate, recordings were made from taste-responsive neurons in the cortical taste areas in macaques. Most of the neurons were in the orbitofrontal cortex (secondary) taste area. First, it was shown that there is a representation of the taste of glutamate that is separate from the representation of the other prototypical tastants, sweet (glucose), salt (NaCl), bitter (quinine) and sour (HCl). Second, it was shown that single neurons that had their best responses to sodium glutamate also had good responses to glutamic acid. Third, it was shown that the responses of these neurons to the nucleotide umami tastant inosine 5'-monophosphate were more correlated with their responses to monosodium glutamate than to any prototypical tastant. Fourth, concentration-response curves showed that concentrations of monosodium glutamate as low as 0.001 mol/L were just above threshold for some of these neurons. Fifth, some neurons in the orbitofrontal region which responded to monosodium glutamate and other food tastes, decreased their responses after feeding with monosodium glutamate to behavioral satiety, revealing a mechanism of satiety. In some cases, this reduction was sensory-specific. Sixth, it was shown in psychophysical experiments in humans that the flavor of umami is strongest with a combination of corresponding taste and olfactory stimuli (e.g., monosodium glutamate and garlic odor). The hypothesis is proposed that part of the way in which glutamate works as a flavor enhancer is by acting in combination with corresponding food odors. The appropriate associations between the odor and the glutamate taste may be learned at least in part by olfactory to taste association learning in the primate orbitofrontal cortex.

Reward processing in primate orbitofrontal cortex and basal ganglia.

This article reviews and interprets neuronal activities related to the expectation and delivery of reward in the primate orbitofrontal cortex, in comparison with slowly discharging neurons in the striatum (caudate, putamen and ventral striatum, including nucleus accumbens) and midbrain dopamine neurons. Orbitofrontal neurons showed three principal forms of reward-related activity during the performance of delayed response tasks, namely responses to reward-predicting instructions, activations during the expectation period immediately preceding reward and responses following reward. These activations discriminated between different rewards, often on the basis of the animals' preferences. Neurons in the striatum were also activated in relation to the expectation and detection of reward but in addition showed activities related to the preparation, initiation and execution of movements which reflected the expected reward. Dopamine neurons responded to rewards and reward-predicting stimuli, and coded an error in the prediction of reward. Thus, the investigated cortical and basal ganglia structures showed multiple, heterogeneous, partly simultaneous activations which were related to specific aspects of rewards. These activations may represent the neuronal substrates of rewards during learning and established behavioral performance. The processing of reward expectations suggests an access to central representations of rewards which may be used for the neuronal control of goaldirected behavior.

The orbitofrontal cortex and reward.

The primate 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 odors is represented. The orbitofrontal cortex also receives information about the sight of objects and faces from the temporal lobe cortical visual areas, and neurons in it learn and reverse the visual stimulus to which they respond when the association of the visual stimulus with a primary reinforcing stimulus (such as a taste reward) is reversed. However, the orbitofrontal cortex is involved in representing negative reinforcers (punishers) too, such as aversive taste, and in rapid stimulus-reinforcement association learning for both positive and negative primary reinforcers. In complementary neuroimaging studies in humans it is being found that areas of the orbitofrontal cortex (and connected subgenual cingulate cortex) are activated by pleasant touch, by painful touch, by rewarding and aversive taste, and by odor. Damage to the orbitofrontal cortex in humans can impair the learning and reversal of stimulus- reinforcement associations, and thus the correction of behavioral responses when these are no longer appropriate because previous reinforcement contingencies change. This evidence thus shows that the orbitofrontal cortex is involved in decoding and representing some primary reinforcers such as taste and touch; in learning and reversing associations of visual and other stimuli to these primary reinforcers; and in controlling and correcting reward-related and punishment-related behavior, and thus in emotion.

Memory systems in the brain.

The operation of different brain systems involved in different types of memory is described. One is a system in the primate orbitofrontal cortex and amygdala involved in representing rewards and punishers, and in learning stimulus-reinforcer associations. This system is involved in emotion and motivation. A second system in the temporal cortical visual areas is involved in learning invariant representations of objects. A third system in the hippocampus is implicated in episodic memory and in spatial function. Fourth, brain systems in the frontal and temporal cortices involved in short term memory are described. The approach taken provides insight into the neuronal operations that take place in each of these brain systems, and has the aim of leading to quantitative biologically plausible neuronal network models of how each of these memory systems actually operates.

Responses to the Sensory Properties of Fat of Neurons in the Primate Orbitofrontal Cortex

The primate orbitofrontal cortex is a site of convergence of information from primary taste, olfactory, and somatosensory cortical areas. We describe the responses of a population of single neurons in the orbitofrontal cortex that responds to fat in the mouth. The neurons respond, when fatty foods are being eaten, to pure fat such as glyceryl trioleate and also to substances with a similar texture but different chemical composition such as paraffin oil (hydrocarbon) and silicone oil [Si(CH3)2O)n]. This is evidence that the neurons respond to the oral texture of fat, sensed by the somatosensory system. Some of the population of neurons respond unimodally to the texture of fat. Other single neurons show convergence of taste inputs, and others of olfactory inputs, onto single neurons that respond to fat. For example, neurons were found that responded to the mouth feel of fat and the taste of monosodium glutamate (both found in milk), or to the mouth feel of fat and to odor. Feeding to satiety reduces the responses of these neurons to the fatty food eaten, but the neurons still respond to some other foods that have not been fed to satiety. Thus sensory-specific satiety for fat is represented in the responses of single neurons in the primate orbitofrontal cortex. Fat is an important constituent of food that affects its palatability and nutritional effects. The findings described provide evidence that the reward value (or pleasantness) of the mouth feel of fat is represented in the primate orbitofrontal cortex and that the representation is relevant to appetite.

The neurophysiology of taste and olfaction in primates, and umami flavor.

To investigate the neural encoding of glutamate (umami) taste in the primate, recordings were made from taste responsive neurons in the cortical taste areas in macaques. Most of the neurons were in the orbitofrontal cortex (secondary) taste area. First, it was shown that there is a representation of the taste of glutamate which is separate from the representation of the other prototypical tastants sweet (glucose), salt (NaCl), bitter (quinine) and sour (HCl). Second, it was shown that single neurons that had their best responses to sodium glutamate also had good responses to glutamic acid. Third, it was shown that the responses of these neurons to the nucleotide umami tastant inosine 5'-monophosphate were more correlated with their responses to monosodium glutamate than to any prototypical tastant. Fourth, concentration response curves showed that concentrations of monosodium glutamate as low as 0.001 M were just above threshold for some of these neurons. Fifth, some neurons in the orbitofrontal region, which responded to monosodium glutamate and other food tastes, decreased their responses after feeding with monosodium glutamate to behavioral satiety, revealing a mechanism of satiety. In some cases this reduction was sensory-specific. Sixth, it was shown in psychophysical experiments in humans that the flavor of umami is strongest with a combination of corresponding taste and olfactory stimuli (e.g., monosodium glutamate and garlic odor). The hypothesis is proposed that part of the way in which glutamate works as a flavor enhancer is by acting in combination with corresponding food odors. The appropriate associations between the odor and the glutamate taste may be learned at least in part by olfactory to taste association learning in the primate orbitofrontal cortex.

Representation of olfactory information in the primate orbitofrontal cortex.

1. To analyze the information represented about individual odor stimuli in the responses of single olfactory neurons in the primate orbitofrontal area, neuronal responses were measured to a set of seven to nine odorants in macaques performing an olfactory discrimination task. The population of neurons analyzed had responses that were significantly differential to the odorants. 2. Information theoretic analyses were applied to the responses of the neurons, and information measures were calculated from the firing rate of the responses and from the principal components of the responses. The information reflected by the firing rate of the response accounted for the majority of the information present (86%) when compared with the information derived from the first three principal components of the spike train. This indicated that temporal encoding had a very minor role in the encoding of olfactory information by single orbitofrontal olfactory cells. 3. The average information about which odorant was presented, averaged across the 38 neurons, was 0.09 bits, a figure that is low when compared with the information values previously published for the responses of temporal lobe face-selective neurons. 4. Application of information theoretic analyses to the responses of these neurons showed how much information about which stimulus was delivered was present in the responses of individual neurons. It was found that for the majority of the neurons significant amounts of information were reflected about one or two of the odorants presented. 5. For each neuron, the information reflected in the responses of that neuron about the reinforcement value and the information about the identity of the odorants were calculated. It is shown that many neurons carry information about which of the odorants was presented; in addition, some neurons reflect information only about the taste association of the stimuli and not about odorant identity. 6. Measurements of the sparseness of the representation indicated that a broadly distributed representation of the identity of odorants was present in this population of neurons.

Hunger and satiety modify the responses of olfactory and visual neurons in the primate orbitofrontal cortex

1. The primate orbitofrontal cortex is the site of convergence of information from primary taste and primary olfactory cortical regions. In addition, it receives projections from temporal lobe visual areas concerned with the representation of objects such as foods. Previous work has shown that the responses of gustatory neurons in the secondary taste area within the orbitofrontal cortex are modulated by hunger and satiety, in that they stop responding to the taste of a food on which an animal has been fed to behavioral satiation, yet may continue to respond to the taste of other foods. 2. This study demonstrates a similar modulation of the responses of olfactory and visual orbitofrontal cortex neurons after feeding to satiety. Seven of nine olfactory neurons that were responsive to the odors of foods, such as blackcurrant juice, were found to decrease their responses to the odor of the satiating food in a selective and statistically significant manner. 3. It also was found for eight of nine neurons that had selective responses to the sight of food, that they demonstrated a sensory-specific reduction in their visual responses to foods after satiation. 4. The responses of orbitofrontal cortex neurons selective for foods in more than one modality also were analyzed before and after feeding to satiation. Satiety often affected the responses of these multimodal neurons across all modalities, but a sensory-specific effect was not always demonstrable for both modalities. 5. These findings show that the olfactory and visual representations of food, as well as the taste representation of food, in the primate orbitofrontal cortex are modulated by hunger. Usually a component related to sensory-specific satiety can be demonstrated. The findings link at least part of the processing of olfactory and visual information in this brain region to the control of feeding-related behavior.

Olfactory neuronal responses in the primate orbitofrontal cortex: analysis in an olfactory discrimination task

1. The primate orbitofrontal cortex receives inputs from the primary olfactory (pyriform) cortex and also from the primary taste cortex. To investigate how olfactory information is encoded in the orbitofrontal cortex, the responses of single neurons in the orbitofrontal cortex and surrounding areas were recorded during the performance of an olfactory discrimination task. In the task, the delivery of one of eight different odors indicated that the monkey could lick to obtain a taste of sucrose. If one of two other odors was delivered from the olfactometer, the monkey had to refrain from licking, otherwise he received a taste of saline. 2. Of the 1,580 neurons recorded in the orbitofrontal cortex, 3.1% (48) had olfactory responses and 34 (2.2%) responded differently to the different odors in the task. The neurons responded with a typical latency of 180 ms from the onset of odorant delivery. 3. Of the olfactory neurons with differential responses in the task, 35% responded solely on the basis of the taste reward association of the odorants. Such neurons responded either to all the rewarded stimuli, and none of the saline-associated stimuli, or vice versa. 4. The remaining 65% of these neurons showed differential selectivity for the stimuli based on the odor quality and not on the taste reward association of the odor. 5. The findings show that the olfactory representation within the orbitofrontal cortex reflects for some neurons (65%) which odor is present independently of its association with taste reward, and that for other neurons (35%), the olfactory response reflects (and encodes) the taste association of the odor. The additional finding that some of the odor-responsive neurons were also responsive to taste stimuli supports the hypothesis that odor-taste association learning at the level of single neurons in the orbitofrontal cortex enables such cells to show olfactory responses that reflect the taste association of the odor.

Human orbitofrontal cortex: cytoarchitecture and quantitative immunohistochemical parcellation.

The primate orbitofrontal cortex is a component of the paralimbic cortical "belt" and consists of several distinct areas. It is involved in high order association functions that include the integration of emotion, behavior, and various sensory processes. To define the cyto- and chemo-architectonic organization of the human orbitofrontal cortex, we have used antibodies to the nonphosphorylated neurofilament triplet protein and to the calcium-binding proteins parvalbumin and calretinin. Immunohistochemistry revealed labeling patterns corresponding to the cytoarchitecture defined by Nissl preparations. Neurofilament protein-immunoreactive pyramidal neurons were located only in layers V-VI in the agranular posterior orbitofrontal cortex, whereas they were distributed in both layers III and V-VI in the anteromedial and anterolateral granular regions. The intermediate dysgranular portion of the orbitofrontal cortex represented a transition zone with a progressive decrease in layer III labeled pyramidal cell numbers posteriorly. The distribution of parvalbumin- and calretinin-immunoreactive interneurons was more homogeneous, although the posteromedial region and the cortex of the inferior rostral sulcus had slightly lower parvalbumin-positive neuron counts than the other orbitofrontal areas. Parvalbumin immunoreactivity in the neuropil exhibited a high degree of regional specialization in that it was consistently less intense in the cortex of the intermediate and posterior part of the gyrus rectus, whereas the other orbitofrontal areas had a very dense neuropil staining in layers III to V. Also, there was a dense plexus of parvalbumin-immunoreactive fibers restricted to layer I in the posterolateral orbitofrontal cortex, and patches of neuropil staining in layer III of the inferior rostral sulcus. These region-specific neuropil staining patterns may correspond to the distribution of parvalbumin-immunoreactive thalamocortical projections to distinct domains of the orbitofrontal cortex. This regional parcellation of the human orbitofrontal cortex as defined by specific neuronal markers, may represent an anatomical substrate for the localization of the various functions attributed to this poorly understood cortical region.