Human Orbitofrontal Cortex Research Articles

Human processing of behaviorally relevant and irrelevant absence of expected rewards: a high-resolution ERP study.

Acute lesions of the posterior medial orbitofrontal cortex (OFC) in humans may induce a state of reality confusion marked by confabulation, disorientation, and currently inappropriate actions. This clinical state is strongly associated with an inability to abandon previously valid anticipations, that is, extinction capacity. In healthy subjects, the filtering of memories according to their relation with ongoing reality is associated with activity in posterior medial OFC (area 13) and electrophysiologically expressed at 220–300 ms. These observations indicate that the human OFC also functions as a generic reality monitoring system. For this function, it is presumably more important for the OFC to evaluate the current behavioral appropriateness of anticipations rather than their hedonic value. In the present study, we put this hypothesis to the test. Participants performed a reversal learning task with intermittent absence of reward delivery. High-density evoked potential analysis showed that the omission of expected reward induced a specific electrocortical response in trials signaling the necessity to abandon the hitherto reward predicting choice, but not when omission of reward had no such connotation. This processing difference occurred at 200–300 ms. Source estimation using inverse solution analysis indicated that it emanated from the posterior medial OFC. We suggest that the human brain uses this signal from the OFC to keep thought and behavior in phase with reality.

A Potential Role for a Genetic Variation of AKAP5 in Human Aggression and Anger Control

The A-kinase-anchoring protein 5 (AKAP5), a post-synaptic multi-adaptor molecule that binds G-protein-coupled receptors and intracellular signaling molecules has been implicated in emotional processing in rodents, but its role in human emotion and behavior is up to now still not quite clear. Here, we report an association of individual differences in aggressive behavior and anger expression with a functional genetic polymorphism (Pro100Leu) in the human AKAP5 gene. Among a cohort of 527 young, healthy individuals, carriers of the less common Leu allele (15.6% allele frequency) scored significantly lower in the physical aggression domain of the Buss and Perry Aggression Questionnaire and higher in the anger control dimension of the state-trait anger expression inventory. In a functional magnetic resonance imaging experiment we could further demonstrate that AKAP5 Pro100Leu modulates the interaction of negative emotional processing and executive functions. In order to investigate implicit processes of anger control, we used the well-known flanker task to evoke processes of action monitoring and error processing and added task-irrelevant neutral or angry faces in the background of the flanker stimuli. In line with our predictions, Leu carriers showed increased activation of the anterior cingulate cortex (ACC) during emotional interference, which in turn predicted shorter reaction times and might be related to stronger control of emotional interference. Conversely, Pro homozygotes exhibited increased orbitofrontal cortex (OFC) activation during emotional interference, with no behavioral advantage. Immunohistochemistry revealed AKAP5 expression in post mortem human ACC and OFC. Our results suggest that AKAP5 Pro100Leu contributes to individual differences in human aggression and anger control. Further research is warranted to explore the detailed role of AKAP5 and its gene product in human emotion processing.

Chemosensory Learning in the Cortex

Taste is a primary reinforcer. Olfactory–taste and visual–taste association learning takes place in the primate including human orbitofrontal cortex to build representations of flavor. Rapid reversal of this learning can occur using a rule-based learning system that can be reset when an expected taste or flavor reward is not obtained, that is by negative reward prediction error, to which a population of neurons in the orbitofrontal cortex responds. The representation in the orbitofrontal cortex but not the primary taste or olfactory cortex is of the reward value of the visual/olfactory/taste input as shown by devaluation experiments in which food is fed to satiety, and by correlations of the activations with subjective pleasantness ratings in humans. Sensory-specific satiety for taste, olfactory, visual, and oral somatosensory inputs produced by feeding a particular food to satiety is implemented it is proposed by medium-term synaptic adaptation in the orbitofrontal cortex. Cognitive factors, including word-level descriptions, modulate the representation of the reward value of food in the orbitofrontal cortex, and this effect is learned it is proposed by associative modification of top-down synapses onto neurons activated by bottom-up taste and olfactory inputs when both are active in the orbitofrontal cortex. A similar associative synaptic learning process is proposed to be part of the mechanism for the top-down attentional control to the reward value vs. the sensory properties such as intensity of taste and olfactory inputs in the orbitofrontal cortex, as part of a biased activation theory of selective attention.

Beyond Reversal: A Critical Role for Human Orbitofrontal Cortex in Flexible Learning from Probabilistic Feedback

Damage to the orbitofrontal cortex (OFC) has been linked to impaired reinforcement processing and maladaptive behavior in changing environments across species. Flexible stimulus-outcome learning, canonically captured by reversal learning tasks, has been shown to rely critically on OFC in rats, monkeys, and humans. However, the precise role of OFC in this learning remains unclear. Furthermore, whether other frontal regions also contribute has not been definitively established, particularly in humans. In the present study, a reversal learning task with probabilistic feedback was administered to 39 patients with focal lesions affecting various sectors of the frontal lobes and to 51 healthy, demographically matched control subjects. Standard groupwise comparisons were supplemented with voxel-based lesion-symptom mapping to identify regions within the frontal lobes critical for task performance. Learning in this dynamic stimulus-reinforcement environment was considered both in terms of overall performance and at the trial-by-trial level. In this challenging, probabilistic context, OFC damage disrupted both initial and reversal learning. Trial-by-trial performance patterns suggest that OFC plays a critical role in interpreting feedback from a particular trial within the broader context of the outcome history across trials rather than in simply suppressing preexisting stimulus-outcome associations. The findings show that OFC, and not other prefrontal regions, plays a necessary role in flexible stimulus-reinforcement learning in humans.

Intracerebral gamma modulations reveal interaction between emotional processing and action outcome evaluation in the human orbitofrontal cortex

The orbitofrontal cortex (OFC) plays a key role not only in processing emotions but also in monitoring performance outcome. Although the neuroanatomical substrates underlying each of the two processes have been extensively investigated, they have predominantly been probed separately and therefore a precise knowledge of the functional overlap within the multiple OFC sub-portions involved is still lacking. Here, we explore the neural dynamics mediating performance monitoring and emotional processing using direct intracranial EEG (iEEG) recordings from multiple OFC sites of an epileptic patient. Neural activity was recorded during two experiments. The first task required processing of emotional faces and the second investigated action outcome evaluation based on a visual feedback on the subject's performance. Task-related neural dynamics were assessed using modulations of high frequency responses in the gamma-band (50–150 Hz). Our results reveal that processing negative facial emotions as well as receiving negative feedback both elicited gamma-band responses in the lateral OFC. By contrast, the mid-OFC was selectively activated for positive feedback. Furthermore, we also found significant gamma-band deactivation in the gyrus rectus during processing of negative feedback. Our findings provide novel evidence for an intricate valence-selective interaction between the networks mediating emotion processing and performance monitoring in human OFC and support the hypothesis of a tight relationship between gamma-band activity and behavior.

The architecture of reward value coding in the human orbitofrontal cortex.

To ensure their survival, animals exhibit a number of reward-directed behaviors, such as foraging for food or searching for mates. This suggests that a core set of brain regions may be shared by many species to process different types of rewards. Conversely, many new brain areas have emerged over the course of evolution, suggesting potential specialization of specific brain regions in the processing of more recent rewards such as money. Here, using functional magnetic resonance imaging in humans, we identified the common and distinct brain systems processing the value of erotic stimuli and monetary gains. First, we provide evidence that a set of neural structures, including the ventral striatum, anterior insula, anterior cingulate cortex, and midbrain, encodes the subjective value of rewards regardless of their type, consistent with a general hedonic representation. More importantly, our results reveal reward-specific representations in the orbitofrontal cortex (OFC): whereas the anterior lateral OFC, a phylogenetically recent structure, processes monetary gains, the posterior lateral OFC, phylogenetically and ontogenetically older, processes more basic erotic stimuli. This dissociation between OFC representations of primary and secondary rewards parallels current views on lateral prefrontal cortex organization in cognitive control, suggesting an increasing trend in complexity along a postero-anterior axis according to more abstract representations. Together, our results support a modular view of reward value coding in the brain and propose that a unifying principle of postero-anterior organization can be applied to the OFC.

3-D Cytoarchitectonic parcellation of human orbitofrontal cortex: Correlation with postmortem MRI

The orbitofrontal cortex (OFC) is located on the basal surface of the frontal lobe and is distinguished by its unique anatomical and functional features. Clinical and postmortem studies suggest the involvement of the orbitofrontal cortex in psychiatric disorders. However, the exact parcellation of this cortical region is still a matter of debate. Therefore, the goal of this study is to provide a detailed description of the extent of borders of individual orbitofrontal cortical areas using cytoarchitectonic criteria in a large sample of human brains, which could be applied by independent neuroanatomists. To make this microscopic parcellation useful to neuroimaging studies, magnetic resonance images of postmortem brains in the coronal plane were collected prior to the preparation of coronal histological sections from the same brains. A complete series of coronal sections from 6 normal human brains and partial sections from the frontal cortex of 21 normal human brains were stained with general histological and immunohistochemical methods specific for different cell-types. These sections were examined microscopically by two independent neuroanatomists (HBMU and GR) to achieve reproducible delineations. After the borders were determined, the tissue sections were superimposed on the corresponding magnetic resonance images. Based on our cytoarchitectonical criteria, Brodmann's areas 47 and 11 were included in the human orbitofrontal cortex. Area 47 was further subdivided into three medial (located on the medial, anterior and posterior orbital gyri) and two lateral (located on the lateral orbital gyrus) subareas. In addition, we observed an anterior–posterior gradient in the cytoarchitecture of areas 11 and 47. The transverse orbital sulcus corresponds roughly to the transition between the subregions of the anterior and posterior OFC. Finally, the present delineation is contrasted with an overview of the different published nomenclatures for the OFC parcellation.

The neural code of reward anticipation in human orbitofrontal cortex

An optimal choice among alternative behavioral options requires precise anticipatory representations of their possible outcomes. A fundamental question is how such anticipated outcomes are represented in the brain. Reward coding at the level of single cells in the orbitofrontal cortex (OFC) follows a more heterogeneous coding scheme than suggested by studies using functional MRI (fMRI) in humans. Using a combination of multivariate pattern classification and fMRI we show that the reward value of sensory cues can be decoded from distributed fMRI patterns in the OFC. This distributed representation is compatible with previous reports from animal electrophysiology that show that reward is encoded by different neural populations with opposing coding schemes. Importantly, the fMRI patterns representing specific values during anticipation are similar to those that emerge during the receipt of reward. Furthermore, we show that the degree of this coding similarity is related to subjects' ability to use value information to guide behavior. These findings narrow the gap between reward coding in humans and animals and corroborate the notion that value representations in OFC are independent of whether reward is anticipated or actually received.

Locally distributed coding of reward value in human orbitofrontal cortex

Locally distributed coding of reward value in human orbitofrontal cortex

The Role of Human Orbitofrontal Cortex in Flexible Learning and Value Representation

The Role of Human Orbitofrontal Cortex in Flexible Learning and Value Representation

Orbito-frontal lesions cause impairment during late but not early emotional prosodic processing

The orbitofrontal cortex (OFC) is functionally linked to a variety of cognitive and emotional functions. In particular, lesions of the human OFC lead to large-scale changes in social and emotional behavior. For example, patients with OFC lesions are reported to suffer from deficits in affective decision-making, including impaired emotional face and voice expression recognition (e.g., Hornak et al., 1996, 2003). However, previous studies have failed to acknowledge that emotional processing is a multistage process. Thus, different stages of emotional processing (e.g., early vs. late) in the same patient group could be affected in a qualitatively different manner. The present study investigated this possibility and tested implicit emotional speech processing in an ERP experiment followed by an explicit behavioral emotional recognition task. OFC patients listened to vocal emotional expressions of anger, fear, disgust, and happiness compared to a neutral baseline spoken either with or without lexical content. In line with previous evidence (Paulmann & Kotz, 2008b), both patients and healthy controls differentiate emotional and neutral prosody within 200 ms (P200). However, the recognition of emotional vocal expressions is impaired in OFC patients as compared to healthy controls. The current data serve as first evidence that emotional prosody processing is impaired only at a late, and not at an early processing stage in OFC patients.

The Role of Human Orbitofrontal Cortex in Value Comparison for Incommensurable Objects

The human orbitofrontal cortex is strongly implicated in appetitive valuation. Whether its role extends to support comparative valuation necessary to explain probabilistic choice patterns for incommensurable goods is unknown. Using a binary choice paradigm, we derived the subjective values of different bundles of goods, under conditions of both gain and loss. We demonstrate that orbitofrontal activation reflects the difference in subjective value between available options, an effect evident across valuation for both gains and losses. In contrast, activation in dorsal striatum and supplementary motor areas reflects subjects' choice probabilities. These findings indicate that orbitofrontal cortex plays a pivotal role in valuation for incommensurable goods, a critical component process in human decision making.

Hedonic and Informational Functions of the Human Orbitofrontal Cortex

Functional imaging studies have revealed roles for orbitofrontal cortex (OFC) in reward processing and decision making. In many situations, rewards signal that the current behavior should be maintained, whereas punishments cue a change in behavior. Thus, hedonic responses to reinforcers are conflated with their function as behavioral cues. In an attempt to disambiguate these functions, we performed a functional magnetic resonance imaging study of a 2-choice decision-making task. After each trial, subjects were rewarded or punished and independently provided with a cue to maintain or change behavior. We identified key regions of OFC involved in these processes. An anterior medial focus responded to reward, whereas bilateral lateral foci responded to punishment. The right-sided lateral region that responded to punishment also responded to cues for behavior change (shift), whereas a more ventral and anterior bilateral region responded to cues for behavioral maintenance (stay). The right-sided stay region responded specifically when stay cues were combined with punishment. These results support the view that OFC codes both hedonic responses to reinforcers and their behavioral consequences. Punishments and shift cues are associated with the same right lateral OFC focus, suggesting a fundamental connection between emotive response to negative reinforcement and use of negative information to cue behavioral change.

Architectonic mapping of the medial region of the human orbitofrontal cortex by density profiles

The study of architectonic differentiation in the cortex is advanced by the articulation of objective definitions based on clear features of the cortical architecture. We adopted areal density profiles as a means of sampling the cortex. On the profiles, we isolated and quantified the density of individual cortical layers. These features may serve as criteria in objective definitions in a way that builds on qualitative observations found in the classical literature. A preprocessing procedure was introduced to overcome artefacts in the density profiles caused by the partial overlap of neighboring neuronal layers and cortical folding. We applied this method to the medial half of the orbital frontal cortex in specimens drawn from 10 human postmortem brain hemispheres. The measurements successfully confirmed the existence of several qualitatively observed areas (architectonic areas 14c, 14r, 11m, 11 and 13). The selection of specific sampling parameters was justified on the basis of simultaneous measurements of the cortical morphology which demonstrate its influence on the appearance of the cortical layers. We also examined the robustness of the measuring procedure by analyzing the outcome of varying systematically the sampling parameters. We describe here a novel method of sampling the cortex for architectonic analysis and demonstrate its application on histological sections obtained from the medial half of the human orbitofrontal cortex.

Changes in emotion following lesions of discrete orbitofrontal cortex subregions in the macaque

Event Abstract Back to Event Changes in emotion following lesions of discrete orbitofrontal cortex subregions in the macaque Peter Rudebeck1*, Lily Chau1 and Elisabeth Murray1 1 National Institute of Mental Health, United States Marked changes in affect is one of the hallmarks of damage to or dysfunction within the orbitofrontal cortex (OFC) in both humans and animals. The OFC, however, is not a homogeneous structure. It has been proposed that there may be two subregions, distinct by their cytoarchitecture and connections to other brain structures, which make up the OFC. One of these subregions broadly encompasses Walker’s areas 11/13 while the other centers on Walker’s area 14 and there has been speculation that each might play distinct roles in regulating affect. Direct evidence for this hypothesis, however, is scarce. Damage to the OFC in humans is rarely confined to one subregion alone and studies in animals have generally focused on the OFC as a whole. To explore the contribution of these OFC subregions to emotional processing, restricted excitoxic lesions of either areas 11/13 (n=4) or area 14 (n=4) were made in rhesus monkeys (Macaca mulatta). The emotional responses of these two groups as well as a group of unoperated controls (n=4) were assessed in a series of tasks where monkeys were presented with different objects at the same time as a valued food reward. The latency to retrieve the food reward reflects macaques relative valuation of the object in contrast to the incentive value of the food. In the first task monkey’s latency to retrieve the food reward was assessed in the presence of either static neutral objects or static fear objects (rubber snake or spider) whereas in a second task their responses to moving fearful objects were assessed (moving toy snake and spider). Compared to unoperated controls, monkeys with lesions restricted to either areas 11/13 or area 14 were less likely to retrieve the food reward in the presence of the static rubber spider. These preliminary results, which suggest increased fear in both lesion groups are in contrast with previous reports of macaques with more extensive OFC lesions. Conference: 41st European Brain and Behaviour Society Meeting, Rhodes Island, Greece, 13 Sep - 18 Sep, 2009. Presentation Type: Poster Presentation Topic: Poster presentations Citation: Rudebeck P, Chau L and Murray E (2009). Changes in emotion following lesions of discrete orbitofrontal cortex subregions in the macaque. Conference Abstract: 41st European Brain and Behaviour Society Meeting. doi: 10.3389/conf.neuro.08.2009.09.282 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Jun 2009; Published Online: 12 Jun 2009. * Correspondence: Peter Rudebeck, National Institute of Mental Health, Bethesda, United States, peter.rudebeck@mssm.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Peter Rudebeck Lily Chau Elisabeth Murray Google Peter Rudebeck Lily Chau Elisabeth Murray Google Scholar Peter Rudebeck Lily Chau Elisabeth Murray PubMed Peter Rudebeck Lily Chau Elisabeth Murray Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Face processing in different brain areas, and critical band masking

Neurophysiological evidence is described showing that some neurons in the macaque inferior temporal visual cortex have responses that are invariant with respect to the position, size, view, and spatial frequency of faces and objects, and that these neurons show rapid processing and rapid learning. Critical band spatial frequency masking is shown to be a property of these face-selective neurons and of the human visual perception of faces. Which face or object is present is encoded using a distributed representation in which each neuron conveys independent information in its firing rate, with little information evident in the relative time of firing of different neurons. This ensemble encoding has the advantages of maximizing the information in the representation useful for discrimination between stimuli using a simple weighted sum of the neuronal firing by the receiving neurons, generalization, and graceful degradation. These invariant representations are ideally suited to provide the inputs to brain regions such as the orbitofrontal cortex and amygdala that learn the reinforcement associations of an individual's face, for then the learning, and the appropriate social and emotional responses generalize to other views of the same face. A theory is described of how such invariant representations may be produced by self-organizing learning in a hierarchically organized set of visual cortical areas with convergent connectivity. The theory utilizes either temporal or spatial continuity with an associative synaptic modification rule. Another population of neurons in the cortex in the superior temporal sulcus encodes other aspects of faces such as face expression, eye-gaze, face view, and whether the head is moving. These neurons thus provide important additional inputs to parts of the brain such as the orbitofrontal cortex and amygdala that are involved in social communication and emotional behaviour. Outputs of these systems reach the amygdala, in which face-selective neurons are found, and also the orbitofrontal cortex, in which some neurons are tuned to face identity and others to face expression. In humans, activation of the orbitofrontal cortex is found when a change of face expression acts as a social signal that behaviour should change; and damage to the human orbitofrontal and pregenual cingulate cortex can impair face and voice expression identification, and also the reversal of emotional behaviour that normally occurs when reinforcers are reversed.

Distinguishing expected negative outcomes from preparatory control in the human orbitofrontal cortex

The human orbitofrontal cortex (OFC) plays a critical role in adapting behavior according to the context provided by expected outcomes of actions. However, several aspects of this function are still poorly understood. In particular, it is unclear to what degree any subdivisions of the OFC are specifically engaged when negatively valenced outcomes are expected, and to what extent such areas might be involved in preparatory active control of behavior. We examined these issues in two complementary functional magnetic resonance imaging (fMRI) studies in which we simultaneously and independently manipulated monetary incentives for correct performance, and demands for active preparation of cognitive control. In both experiments, preparation for performance was associated with lateral PFC activity in response to high incentives, regardless of their valence, as well as in response to increased task demands. In contrast, areas of the OFC centered around the lateral orbital sulcus responded maximally to negatively perceived prospects, even when such prospects were associated with decreases in preparatory cognitive control. These results provide direct support for theoretical models which posit that the OFC contributes to behavioral regulation by representing the value of anticipated outcomes, but does not implement active control aimed at avoiding or pursuing outcomes. Furthermore, they provide additional converging evidence that the lateral OFC is involved in representing specifically the affective impact of anticipated negative outcomes.

Functions of the orbitofrontal and pregenual cingulate cortex in taste, olfaction, appetite and emotion

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. The representation of taste and other food-related stimuli in the orbitofrontal cortex of macaques is found from its lateral border throughout area 13 to within 7 mm of the midline, and in humans the representation of food-related and other pleasant stimuli is found particularly in the medial orbitofrontal cortex. 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. 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 which drives food intake. A neuronal representation of taste is also found in the pregenual cingulate cortex, which receives inputs from the orbitofrontal cortex, and in humans many pleasant stimuli activate the pregenual cingulate cortex, pointing towards this as an important area in motivation and emotion.

The aging human orbitofrontal cortex: Decreasing polyunsaturated fatty acid composition and associated increases in lipogenic gene expression and stearoyl-CoA desaturase activity

Orbitofrontal cortex (OFC, Brodmann area 10) gray matter volume reductions and selective reductions in docosahexaenoic acid (DHA, 22:6 n-3) are observed in adult patients with major depressive disorder (MDD). OFC gray matter volume also decreases with advancing age in healthy subjects. To examine if OFC gray matter DHA composition decreases during normal aging, we determined age-related changes in OFC gray matter fatty acid composition by gas chromatography in subjects aged 29–80 years ( n=30). We additionally determined elongase ( HELO1), delta-5 desaturase ( FASD1), delta-6 desaturase ( FASD2), peroxisomal ( PEX19), and stearoyl-CoA desaturase ( SCD) mRNA expression in the same tissues. Increasing age was associated with a progressive decline in polyunsaturated fatty acid (PUFA) composition, including DHA and arachidonic acid (AA, 20:4 n-6), and transient, apparently compensatory, elevations in elongase and desaturase gene expression. The age-related reduction in PUFA composition was inversely correlated with SCD expression and activity resulting in elevations in monounsaturated fatty acid composition. These dynamic age-related changes in OFC gray matter fatty acid composition and biosynthetic gene expression may contribute to the progressive decline in OFC gray matter volume found with advancing age. The implications of age-related reductions in OFC PUFA composition for affective dysregulation in the elderly are discussed.

Elevated cytokine expression in the orbitofrontal cortex of victims of suicide

Based on the reported association between cytokines with depression and suicide, and evidence of increased markers of inflammation in the brain of suicide victims, the present study examined the expression of cytokines in the orbitofrontal cortex of suicide victims. In a postmortem sample obtained from the Brodman area 11 of suicides (n = 34) and controls (n = 17), real-time RT-PCR was used to compare the expression of mRNA species for tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, 4, 5, 6, and 13. Increased expression of IL-4 was found in women suicide victims and IL-13 in men suicide victims. Elevated but not significant cytokine expression was also observed for TNF-alpha in women suicide victims. To our knowledge, these results provide the first evidence of the presence of mRNA transcripts of type 2 T-helper cytokines in the human orbitofrontal cortex and their increased expression in the brain of suicides.