Differential activity in the OFC in response to a range of emotional cues

The above studies used affective facial expressions as stimuli. It is well known that faces are processed by specialized neurons in different brain areas including the frontal cortex (e.g. Scalaidhe, 1999). Hence, it seems conceivable that the effects reported above are partly due to the outstanding characteristics of facial stimuli. To counteract this objection, studies are reported in the following that used picture sets of more general and to a great extent ‘face-free’ emotional depictions with high motivational relevance.

An animal study with rats (Schoenbaum, 1998) provides evidence that the OFC responds to behaviorally significant stimuli of both, negative and positive valence. In a go/no-go odor discrimination task, rats learned an adaptive behavioral strategy of responding to an odor that predicted a rewarding outcome and of withholding the response when an odor signalled an aversive outcome. Activity in OFC and basolateral amygdala was measured in the learning phase of the task before the rats reached the behavioral criterion. The recording period was a short variable delay interval between the offset of the respective odor and the onset of delivery of the rewarding/punishing outcome (either a tasteful or an aversive fluid).

The activity in the amygdala and OFC during both rewarding and punishing trials increased relative to the pre-trial baseline. In addition, a differential neural response depending on the outcome was seen in both structures. A substantial population of cells fired significantly more often in the aversive than in the rewarding go trials. This differential neural response occurred although the rats had not yet learned the adaptive behavioral odor discrimination. This means that neurons had acquired a discriminatory ability in advance of behavioral adaptation. The activity of cells in the OFC and the amygdala was modulated by the anticipation of either positive or negative consequences. Further, it was found that the relative neural response selectivity increased significantly as rats became more confident in their behavioral discrimination across acquisitions. Thus, elevated activity in the OFC is determined by a subject’s expectancy for reward or punishment. The OFC and the amygdala are strongly involved in the regulation of adaptive goal-directed behavior. Both structures form a functional cooperation with distinguishable specialized assignments.

The speed of the orbitofrontal response to aversive stimuli was demonstrated by Kawasaki and colleagues (2001). They recorded single-neuron responses to

affective slides taken from the IAPS and to different emotional facial expressions taken from the standardized Pictures of Facial Affect (Ekman, 1976). The subject was an otherwise healthy patient who had a history of epilepsy and underwent neurosurgical intervention. Depth electrodes were implanted in ventral and medial prefrontal cortex to record the neural firing rates while the patient watched the affective stimuli. In response to aversive stimuli an initial short-latency transient inhibition of the firing rate was replaced quickly by a prolonged excitation in the medial areas of prefrontal cortex. For neutral stimuli firing rates stayed the same pre and post stimulus presentation. The differential responses to aversive material became significant as soon as 120ms after stimulus onset. It was hypothesized that the observed responses may indicate increased emotional arousal elicited by stimuli signalling threat or danger.

Whereas most studies investigated orbitofrontal function with PET or fMRI, few employed MEG as a functional measure. In a combined fMRI/MEG study, Northoff et al. (2000) demonstrated a functional dissociation between medial orbitofrontal and lateral prefrontal activation in response to stimuli of different valence. In an emotional-motor stimulation, subjects viewed positive, negative, and neutral pictures from the IAPS and they had to press a button as soon as a new picture appeared.

fMRI measurements registered increased medial orbitofrontal activation only when negative pictures were shown. In addition, a significant negative correlation was found between activity in medial orbitofrontal and lateral prefrontal cortex. In contrast, lateral prefrontal activity that was negatively correlated with activity in orbitofrontal cortex, emerged in response to positive slides. Neutral pictures did not change activity in these two regions. MEG analyses were in line with this differential activity pattern: equivalent current dipoles of the early magnetic field were localized in medial and anterior orbitofrontal cortex for the negative and in either lateral orbitofrontal or lower lateral prefrontal cortex for the positive images. The non-emotional neutral condition did not produce early orbitofrontal dipoles. Further, dipole onset was significantly earlier for the negative compared to the positive pictures. No lateralized effects were found. The differential activity pattern observed in response to negative and positive emotion processing points towards a functional dissociation of medial and lateral orbitofrontal regions. It may be argued that the anterior/medial region is functionally involved in negative emotional processing while the lateral region may

serve the function of forming associations between emotions and thoughts (Drevets, 1998).

These findings can be explained by cytoarchitectonic and connectional differences between the two regions: the medial orbitofrontal cortex bears an agranular or dysgranular structure and has connections to the hippocampus, ventrolateral parts of the basal nucleus of the amygdala, dorsolateral prefrontal cortex, dorsomedial parts of mediodorsal thalamic nucleus and anterior cingulum. On the other hand the lateral orbitofrontal cortex features a granular cytoarchitecture and holds connections to the ento-/perirhinal cortex, ventromedial parts of the basal nucleus of the amygdala, dorsolateral prefrontal cortex, ventromedial parts of the mediodorsal thalamis nucleus, premotor cortex, parietal cortex and posterior cingulum (Morecraft, 1992; Carmichael, 1996).

The outlined studies provide clear evidence for OFC activity in response to a variety of different aversive and appetitive visual stimuli. Emotional arousal seems to mediate this activation. The OFC integrates and organizes information and selects an adequate behavior that depends on the expected punishing or rewarding consequences of a stimulus.

2.3.4 Conclusions

In conclusion, OFC activation follows the perception of evocative stimuli that are subjectively relevant for operant goal-directed behavior (Vuilleumier, 2001;

Schoenbaum, 1998). After learning that certain stimuli are associated with reward or punishment , the OFC initiates behavioral alterations whenever the stimulus is present, to cope with it and to adapt to the environment. Stimuli differ in their behavioral significance that depends on their potential consequences. A strongly aversive stimulus that signals severe threat or harm elicits pronounced orbitofrontal activation. With increasing intensity of the threatening stimulus the orbitofrontal areas respond with a proportional augmentation of activity (Blair, 1999). Although activity in OFC can be elicited by any emotionally significant stimulus, anterior and medial areas are particularly specialized for the processing of aversive cues (Northoff, 2000). Patients with damage of the OFC report a diminished or even complete absence of the subjective perception of fear (Hornak, 1996). The OFC has extensive

connections with the amygdala (McDonald, 1991). Both structures form a functional unit and are part of a brainstem-amygdala-cortical alarm system that reacts differentially and rapidly to stimuli signalling potential threat to the self (Kawasaki, 2001). The OFC keeps a memory of formerly learned stimulus-reward/punishment-contingencies in the process of environmental adaptation (Tremblay & Schultz, 2000). This enables an organism to react quickly and adequately in dangerous or threatening situations.