Human Orbitofrontal Cortex Research Articles

The Role of the Human Orbitofrontal Cortex in Taste and Flavor Processing

The human orbitofrontal cortex (OFC) plays an important role in representing taste, flavor, and food reward. The primary role of the OFC in taste is thought to be the encoding of affective value and the computation of perceived pleasantness. The OFC also encodes retronasal olfaction and oral somatosensation. During eating, distinct sensory inputs fuse into a unitary flavor percept, and there is evidence that this percept is encoded in the orbital cortex. Studies examining the effect of internal state on neural representation of food and drink further suggest that processing in the OFC is critical for representing the reward value of foods. Thus, it is likely that, in addition to serving as higher-order gustatory cortex, the OFC integrates multiple sensory inputs and computes reward value to guide feeding behavior.

What Can an Orbitofrontal Cortex‐Endowed Animal Do with Smells?

It is widely presumed that odor quality is a direct outcome of odorant molecular structure, but increasing evidence suggests that learning, experience, and context play important roles in human olfactory perception. Such data suggest that a given set of olfactory receptors activated by an odorant does not map directly onto a given odor percept. Rather, odor perception may rely on more synthetic, or integrative, mechanisms subserved by higher-order brain regions. Results presented here explore the specific role of human orbitofrontal cortex (OFC) in the formation and modulation of odor quality coding. Combining olfactory psychophysical techniques and functional imaging approaches, we have found that sensory-specific information about an odorant is not static or fixed within human olfactory OFC, but is highly malleable and can be rapidly updated by perceptual experience. Critically, the magnitude of OFC activation predicts subsequent behavioral improvement in olfactory perception. Our findings highlight the pivotal role of OFC in linking olfactory sensation, perception, and experience. It is worth considering that many of the current proposed functions attributed to the (distinctively mammalian) OFC are an extension of mechanisms that originally evolved to mediate response flexibility between chemosensory signals and appropriate behavioral actions.

Lights, Camembert, Action! The Role of Human Orbitofrontal Cortex in Encoding Stimuli, Rewards, and Choices

This review outlines some of the main conclusions about the contributions of the orbitofrontal cortex to reward learning and decision making arising from functional neuroimaging studies in humans. It will be argued that human orbitofrontal cortex is involved in a number of distinct functions: signaling the affective value of stimuli as they are perceived, encoding expectations of future reward, and updating these expectations, either by making use of prediction error signals generated in the midbrain, or by using knowledge of the rules or structure of the decision problem. It will also be suggested that this region contributes to the decision making process itself, by encoding signals that inform an individual about what action to take next. Evidence for functional specialization within orbitofrontal cortex in terms of valence will also be evaluated, and the possible contributions of the orbitofrontal cortex in representing the values of actions as well as that of stimuli will be discussed. Finally, some of the outstanding questions for future neuroimaging research of orbitofrontal cortex function will be highlighted.

Understanding the mechanisms of food intake and obesity

Rapid progress is being made in understanding the brain-processing and related psychology of the sensory propertiesof food, and how the satiety (fullness) signals producedduring and after eating regulate appetite. While brain mech-anisms control appetite, a number of sensory and environ-mental factors contribute to overstimulation of the sensorysystems, producing sensory reward signals that are strongerthan can always be controlled easily by satiety signals (1,2).This knowledge makes it seem very likely that, whilesatiety signals have not changed in the last 30 years,changes in the same period in the sensory side of the controlprocess mean that they are now being overridden, contrib-uting to the increasing incidence of obesity. One implica-tion of this work is that, if factors on the sensory side ofthe appetite control process could be regulated, it wouldopen avenues to address obesity prevention and control.From the neuroscience and psychology perspective, thereare, however, many other mechanisms that interact withthe brain and contribute to obesity.

Sensory processing in the brain related to the control of food intake

Complementary neurophysiological recordings in rhesus macaques (Macaca mulatta) and functional neuroimaging in human subjects show that the primary taste cortex in the rostral insula and adjoining frontal operculum provides separate and combined representations of the taste, temperature and texture (including viscosity and fat texture) of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex, these sensory inputs are for some neurons combined by learning with olfactory and visual inputs. Different neurons respond to different combinations, providing a rich representation of the sensory properties of food. In the orbitofrontal cortex feeding to satiety with one food decreases the responses of these neurons to that food, but not to other foods, showing that sensory-specific satiety is computed in the primate (including the human) orbitofrontal cortex. Consistently, activation of parts of the human orbitofrontal cortex correlates with subjective ratings of the pleasantness of the taste and smell of food. Cognitive factors, such as a word label presented with an odour, influence the pleasantness of the odour, and the activation produced by the odour in the orbitofrontal cortex. Food intake is thus controlled by building a multimodal representation of the sensory properties of food in the orbitofrontal cortex and gating this representation by satiety signals to produce a representation of the pleasantness or reward value of food that drives food intake. Factors that lead this system to become unbalanced and contribute to overeating and obesity are described.

Distribution of ICAM-1 immunoreactivity during aging in the human orbitofrontal cortex

Neurological and psychiatric alterations during aging are associated with increased cerebrovascular disturbances and inflammatory markers such as Intercellular Adhesion Molecule-1 (ICAM-1). We investigated whether the distribution of ICAM-1 immunoreactivity (ICAM-1-I) in histological sections from the left orbitofrontal cortex (ORB) was altered during normal aging. Postmortem tissue from the ORB of nine younger (27–54 years old) and 10 older (60–86) human subjects was collected. Cryostat sections were immunostained only with antibodies to ICAM-1 or together with an antibody to glial fibrillary acidic protein (GFAP). The total area fraction of ICAM-1-I, and the fraction of vascular and extravascular ICAM-1-I were quantified in the gray matter. Furthermore, we examined the association of extravascular ICAM-1-I to GFAP immunoreactive (GFAP-IR) astrocytes. In all subjects, brain blood vessels were similarly ICAM-1 immunoreactive, and in some subjects there was a variable number of extravascular patches of ICAM-1-I. The area fraction of ICAM-1-I was 120% higher ( p < .0001) in the old subjects than in the young subjects. This increase localized mostly to the extravascular ICAM-1-I in register with GFAP-IR astrocytes. A much smaller, also age-dependent increase occurred in vascular ICAM-1-I. Our results indicate a dramatic increase in extravascular ICAM-1-I associated to GFAP-IR astrocytes in the ORB in normal aging. This increase may contribute to an enhanced risk for brain inflammatory processes during aging, although a role of extravascular ICAM-1 as a barrier to further inflammation cannot be ruled out.

Brain mechanisms underlying flavour and appetite

Complementary neurophysiological recordings in macaques and functional neuroimaging in humans show that the primary taste cortex in the rostral insula and adjoining frontal operculum provides separate and combined representations of the taste, temperature and texture (including viscosity and fat texture) of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex, these sensory inputs are for some neurons combined by learning with olfactory and visual inputs. Different neurons respond to different combinations, providing a rich representation of the sensory properties of food. In the orbitofrontal cortex, feeding to satiety with one food decreases the responses of these neurons to that food, but not to other foods, showing that sensory-specific satiety is computed in the primate (including human) orbitofrontal cortex. Consistently, activation of parts of the human orbitofrontal cortex correlates with subjective ratings of the pleasantness of the taste and smell of food. Cognitive factors, such as a word label presented with an odour, influence the pleasantness of the odour and the activation produced by the odour in the orbitofrontal cortex. These findings provide a basis for understanding how what is in the mouth is represented by independent information channels in the brain; how the information from these channels is combined; and how and where the reward and subjective affective value of food is represented and is influenced by satiety signals. Activation of these representations in the orbitofrontal cortex may provide the goal for eating, and understanding them helps to provide a basis for understanding appetite and its disorders.

Brain mechanisms of emotion and decision-making

Emotions can be defined as states elicited by rewarding and punishing stimuli. The thesis is being developed that brains are designed around reward and punishment evaluation systems, because this is the way that genes can build a complex system that will produce appropriate but flexible decisions to increase their fitness.Direct neurophysiological and neuroimaging evidence is being obtained that primary (unlearned and gene-specified) reinforcers such as taste, pleasant touch, pain, oral texture including viscosity and fat texture, and oral temperature are decoded and represented in the orbitofrontal cortex of primates including humans. Similarly, previously neutral stimuli such as the sight of an object become associated with primary reinforcers by rapid and reversible stimulus–reinforcement learning implemented in the orbitofrontal cortex. Neuroimaging studies in humans show that reinforcers produced by taste, smell, touch, abstract monetary reward and social reinforcers are represented in the orbitofrontal cortex, and that the orbitofrontal cortex is also activated when an expected reward is not obtained. Neuroimaging studies are also showing strong effects of cognitive inputs on representations of rewards and punishers in the orbitofrontal cortex. The human orbitofrontal cortex is further implicated in decision-making by findings that visual discrimination reversal learning, and emotional behaviour and subjective emotional experience, are impaired in humans with discrete lesions of the orbitofrontal cortex, who may also be impulsive in their decision-making.

Face-selective and auditory neurons in the primate orbitofrontal cortex

Neurons with responses selective for faces are described in the macaque orbitofrontal cortex. The neurons typically respond 2-13 times more to the best face than to the best non-face stimulus, and have response latencies which are typically in the range of 130-220 ms. Some of these face-selective neurons respond to identity, and others to facial expression. Some of the neurons do not have different responses to different views of a face, which is a useful property of neurons responding to face identity. Other neurons have view-dependent responses, and some respond to moving but not still heads. The neurons with face expression, face movement, or face view-dependent responses would all be useful as part of a system decoding and representing signals important in social interactions. The representation of face identity is also important in social interactions, for it provides some of the information needed in order to make different responses to different individuals. In addition, some orbitofrontal cortex neurons were shown to be tuned to auditory stimuli, including for some neurons, the sound of vocalizations. The findings are relevant to understanding the functions of the primate including human orbitofrontal cortex in normal behaviour, and to understanding the effects of damage to this region in humans.

The human orbitofrontal cortex: linking reward to hedonic experience

Hedonic experience is arguably at the heart of what makes us human. In recent neuroimaging studies of the cortical networks that mediate hedonic experience in the human brain, the orbitofrontal cortex has emerged as the strongest candidate for linking food and other types of reward to hedonic experience. The orbitofrontal cortex is among the least understood regions of the human brain, but has been proposed to be involved in sensory integration, in representing the affective value of reinforcers, and in decision making and expectation. Here, the functional neuroanatomy of the human orbitofrontal cortex is described and a new integrated model of its functions proposed, including a possible role in the mediation of hedonic experience.

Physical and physiological consequences of passive intra-oral shimming

Imaging the human orbitofrontal cortex (OFC) with fMRI is problematic due to the proximity of this region to the air-filled sinuses, which causes susceptibility artifacts. Placing a strongly diamagnetic material into the mouth (‘mouthshim’) of a human volunteer can significantly reduce the artifacts in this region. Using the same combined olfactory and visual fMRI paradigm, we compared brain activation and static B 0 field maps of participants being scanned both with and without the ‘mouthshim’. Results demonstrate that the device improves the B 0 field homogeneity within OFC, resulting in significantly stronger BOLD activation in this region. However, the device also caused both increased head motion and reduced activation in insular cortices due to more frequent swallowing and tactile stimulation of the tongue. The ‘mouthshim’ should only, therefore, be used where sensitivity in OFC regions is paramount.

Taste, olfactory, and food texture processing in the brain, and the control of food intake

Complementary neurophysiological recordings in macaques and functional neuroimaging in humans show that the primary taste cortex in the rostral insula and adjoining frontal operculum provides separate and combined representations of the taste, temperature, and texture (including viscosity and fat texture) of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex, these sensory inputs are for some neurons combined by learning with olfactory and visual inputs. Different neurons respond to different combinations, providing a rich representation of the sensory properties of food. In the orbitofrontal cortex, feeding to satiety with one food decreases the responses of these neurons to that food, but not to other foods, showing that sensory-specific satiety is computed in the primate (including human) orbitofrontal cortex. Consistently, activation of parts of the human orbitofrontal cortex correlates with subjective ratings of the pleasantness of the taste and smell of food. Cognitive factors, such as a word label presented with an odour, influence the pleasantness of the odour, and the activation produced by the odour in the orbitofrontal cortex. These findings provide a basis for understanding how what is in the mouth is represented by independent information channels in the brain; how the information from these channels is combined; and how and where the reward and subjective affective value of food is represented and is influenced by satiety signals. Activation of these representations in the orbitofrontal cortex may provide the goal for eating, and understanding them helps to provide a basis for understanding appetite and its disorders.

Learning to Like: A Role for Human Orbitofrontal Cortex in Conditioned Reward

A great deal of human behavior and motivation is based on the intrinsic emotional significance of rewarding or aversive events, as well as on the associations formed between such emotional events and concurrent environmental stimuli. Recent functional neuroimaging studies have implicated the ventral striatum, orbitofrontal cortex (OFC), and amygdala in the representation of reward values and/or in the anticipation of rewarding events. Here, we use functional magnetic resonance imaging to compare brain activation during the presentation of reward with that during presentation of (conditioned) stimuli that have been paired previously with reward. Specifically, we aimed to investigate conditioned reward in the absence of explicit reward anticipation. Twenty-two healthy volunteers were scanned while monochrome visual patterns were incidentally associated with reward or negative feedback in the context of a simple card game. In the subsequent session, visual patterns, including the conditioned stimuli, were presented without reward or negative feedback, and the affective valence of these stimuli was assessed behaviorally. The presentation of reward compared with negative feedback activated the ventral striatum and OFC. Activation in the same OFC region was observed when, in the subsequent session, subjects passively viewed the stimuli that had been paired with reward, without the administration of reward and with subjects being essentially unaware of the conditioning manipulation. These findings suggest that the OFC in humans plays an important role in the representation of both rewarding stimuli and conditioned stimuli that have acquired reward value.

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.

High frequency activities in the human orbitofrontal cortex in sleep–wake cycle

We recorded human orbitofrontal electrocorticogram during wakefulness and sleep in epileptic patients using subdural electrodes. During wakefulness and rapid eye movement (REM) sleep, we observed beta activity in the raw orbitofrontal signals. Power spectral analysis demonstrated beta enhancement during wakefulness and REM sleep when compared to slow wave sleep (SWS). During the phasic REM periods, the beta power was significantly lower than during the tonic REM periods. Gamma enhancement manifested itself in four out of six subjects during the phasic periods. This study is the first that has focused on electrical activity in the human orbitofrontal cortex. Although the role of the orbitofrontal cortex during sleep still remains unclear, high frequency activities give us important suggestions in elucidating the human sleep mechanism.

Taste and Related Systems in Primates Including Humans

The cortical processing of taste and related sensory inputs is being investigated at the neuronal level in macaques to help understand the operation of these cortical areas in humans. The primary taste cortex of macaques in the rostral insula and adjoining frontal operculum contains neurons tuned to different tastes including umami (Scott et al., 1986; Yaxley et al., 1990; Baylis and Rolls, 1991; Rolls et al., 1996b, 1998). Neurons in the macaque primary taste cortex respond to the identity and intensity of taste, in that their responses are not affected when taste reward is decreased to zero by feeding to satiety (Rolls et al., 1988). Other neurons in the primary taste cortex respond to somatosensory inputs by representing the viscosity of what is in the mouth, oral fat texture, the temperature of what is in the mouth, capsaicin (Verhagen et al., 2004), and tannic acid (astringency) (Critchley and Rolls, 1996a). Not only are these qualities represented independently by different neurons, but other neurons respond to combinations of these inputs (Verhagen et al., 2004). The macaque primary taste cortex does not represent the smell or sight of food (Verhagen et al., 2004). The macaque orbitofrontal cortex contains the secondary taste and olfactory cortices, in that different parts of it receive from the primary taste cortex (Baylis et al., 1995), and the primary olfactory cortical areas. Neurons in the secondary taste cortex not only represent taste, but other neurons respond to somatosensory inputs by representing the viscosity of what is in the mouth (Rolls et al., 2003b), oral fat texture (Rolls et al., 1999; Verhagen et al., 2003), the temperature of what is in the mouth (Kadohisa et al., 2004), capsaicin (Kadohisa et al., 2004) and tannic acid (astringency) (Critchley and Rolls, 1996a). Other neurons respond to combinations of these inputs. The orbitofrontal cortex also contains neurons that respond to olfactory stimuli and to the sight of food, and for many neurons these olfactory and taste representations are learned by olfactory to taste or visual to taste associative learning (Rolls and Baylis, 1994; Rolls et al., 1996a; Critchley and Rolls, 1996b). Orbitofrontal cortex neurons represent the reward value of what is in the mouth, in that the neuronal responses to the taste, smell, and sight of food decrease to zero as the monkey is fed to satiety (Rolls et al., 1989; Critchley and Rolls, 1996c). Further, orbitofrontal cortex neurons represent sensory-specific reductions in their responses to the particular foods that have been eaten to satiety, and thus implement sensory-specific satiety (Rolls et al., 1999; Critchley and Rolls, 1996c; Rolls, 1999, 2004). In human functional neuroimaging studies, it has been shown that activation of the orbitofrontal cortex (OFC) and adjoining anterior cingulate cortex (ACC) by odours (O’Doherty et al., 2000) and by liquid food (Kringelbach et al., 2003) is hunger-dependent, and indeed the pleasantness of the food is correlated with the degree of activation found. In both studies, it was shown that the modulation is sensory-specific, so that sensory-specific satiety is implemented in the human OFC. The viscosity of food is represented in the human taste and non-taste insula, and in the orbitofrontal cortex (De Araujo and Rolls, 2004). Fat in the mouth is detected by its texture, and this is represented in the anterior cingulate and orbitofrontal cortex (De Araujo and Rolls, 2004). The pleasantness of odours is represented in the orbitofrontal cortex (Rolls et al., 2003a), and flavour representations are formed by combining taste and olfactory inputs in the orbitofrontal cortex (De Araujo et al., 2003b). This primate neurophysiological and human functional neuroimaging evidence thus shows that the orbitofrontal cortex is involved in decoding some primary reinforcers such as taste, odour, texture, touch and temperature; in learning and reversing associations of visual and other stimuli to these primary reinforcers; and in representing the pleasantness of food in a way that correlates directly with whether food is eaten. The orbitofrontal cortex and connected areas play key roles in representing the sensory qualities and affective value of food, and thus in the control of eating (Rolls et al., 1990; Rolls, 1997, 1999, 2000, 2001a,b, 2005; O’Doherty et al., 2001; Rolls and Scott, 2003; Kringelbach and Rolls, 2004).

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.

Human orbitofrontal cortex mediates extinction learning while accessing conditioned representations of value.

In extinction, an animal learns that a previously conditioned stimulus (CS+) no longer predicts delivery of a salient reinforcer (unconditioned stimulus, UCS). Rodent studies indicate that extinction relies on amygdala-prefrontal interactions and involves formation of memories that inhibit, without actually erasing, the original conditioning trace. Whether extinction learning in humans follows similar neurobiological principles is unknown. We used functional magnetic resonance imaging to measure human brain activity evoked during olfactory aversive conditioning and extinction learning. Neural responses in orbitofrontal cortex and amygdala were preferentially enhanced during extinction, suggesting potential cross-species preservation of learning mechanisms that oppose conditioning. Moreover, by manipulating UCS aversiveness via reinforcer inflation, we showed that a CS+ retains access to representations of UCS value in distinct regions of ventral prefrontal cortex, even as extinction proceeds.

The human orbitofrontal cortex monitors outcomes even when no reward is at stake

The orbitofrontal cortex (OFC) processes the occurrence or omission of anticipated rewards, but clinical evidence suggests that it might serve as a generic outcome monitoring system, independent of tangible reward. In this positron emission tomography (PET) study, normal human subjects performed a series of tasks in which they simply had to predict behind which one of two colored rectangles a drawing of an object was hidden. While all tasks involved anticipation in that they had an expectation phase between the subject’s prediction and the presentation of the outcome, they varied with regards to the uncertainty of outcome. No comment on the correctness of the prediction, no record of ongoing performance, and no reward, not even a score, was provided. Nonetheless, we found strong activation of the OFC: in comparison with a baseline task, the left anterior medial OFC showed activation in all conditions, indicating a basic role in anticipation; the left posterior OFC was activated in all tasks with some uncertainty of outcome, suggesting a role in the monitoring of outcomes; the right medial OFC showed activation exclusively during guessing. The data indicate a generic role of the human OFC, with some topical specificity, in the generation of hypotheses and processing of outcomes, independent of the presence of explicit reward.

Orbitofrontal contribution to auditory encoding

Having recently demonstrated that the human orbitofrontal cortex is selectively activated during the encoding of visual information, we investigated whether this same frontal region, which is directly connected to medial temporal structures, would be activated during the encoding of auditory stimuli. We measured cerebral blood flow (CBF) with positron emission tomography (PET) during the encoding of nonverbal abstract auditory stimuli in a group of young healthy volunteers. The results demonstrate that the left orbitofrontal cortex, area 11 in particular, is involved in the encoding of auditory information. We suggest that the orbitofrontal cortex is a critical frontal region that can exert top-down regulation of other regions of the brain including the medial temporal structures and the lateral frontal cortex, enabling the further processing of information.