In this episode, I am sliding down and under the front part of the brain and consider the orbital frontal cortex, that part of the brain right above and a little behind your eyes. It is much smaller than the lateral gyri on the prefrontal cortex, but appears to be an important probability generator in our brain when we need to consider different options that can result in different rewards or in order to avoid aversive stimuli. The most basic kinds of rewards that neuroscientists can study are for food, because lab animals will respond to those, and while the OFC is definitely intimately related to food, in humans, its powers of prognostication are much more generalized.
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Welcome to PsyDactic, residency edition. Today is July 18, 2023 and I am Dr. O’Leary, a 4th year psychiatry resident in the national capital region. This episode is a continuation of a series I started on the prefrontal cortex. You can go back two episodes if you want to start from the beginning. In the last episode I spent too much time on the dorsolateral prefrontal cortex. Today, I am sliding down and under the front part of the brain to consider the orbital frontal cortex, that part of the brain right above and a little behind your eyes. It is much smaller than the lateral gyri on the prefrontal cortex, but appears to be a super important probability generator in our brain when we need to consider different options that can result in different rewards or in aversive stimuli. The most basic kinds of rewards that neuroscientists can study are for food, because lab animals will respond to those, and while the OFC is definitely intimately related to food, in humans, its powers of prognostication are likely much more generalized.
Let's get started.
Remember when I mentioned that the cortex tends to have six layers of cells. Each layer has it’s own afferents and afferents (neurons that send information into and out of each layer). Each layer also has a number of supporting cells and may contain interneurons that can act to inhibit or excite other neurons within that layer. There are generally two granular layers, called the external and internal granular layers because of their relative locations. Within the OFC there is a gradient where the more posterior cortex is generally lacking layer IV (the internal granular layer), which, when present, would contain neurons from both the thalamus and from other cortical regions in the same hemisphere. This does not mean that the posterior regions of the OFC are entirely disconnected from other cortical and thalamic regions. Just relatively so compared with the more anterior regions of the OFC. For the purpose of this discussion, that is more of a fun fact than anything else, so feel free to impress your friends at your next dinner party.
Just posterior to the OFC are the primary olfactory and gustatory regions, which communicate directly with the posterior OFC. The insula is also posterior to the OFC and communicates directly with it. The posterior OFC also receives somatosensory information especially from the mouth and the hands (interesting), and viscerosensory information, including satiation signals. It processes and then communicates this information forward to the more anterior regions of the OFC, where information is process and shared with the medial PFC and subcortical regions in the striatum, thalamus, medial temporal lobe, hypothalamus and brainstem. It does not have significant communication with the motor or supplementary motor cortex as the dorsolateral prefrontal cortex does. Curiously, it still has its own cortico-striatal-pallido-thalamo-cortico loop similar to that of the motor system. It also communicates back and forth with medial temporal lobe structures: the amygdala, hippocampus and parahippocampal regions and the temporal pole. Like its neighbor, the medial prefrontal cortex, it also is connected to the hypothalamus and periaqueductal gray matter, the ventral tegmental area, and the raphe nuclei, but these projections are relatively weak.
The OFC seems well suited to process information regarding food. It appears to be able to help determine what a potential food source is, whether potential food is attractive or aversive, and what the reward potential is for a food. Donuts, yum. Steamed broccoli, maybe later.
When looking deeper into the orbitofrontal cortex, I ran across a paper titled “What the orbitofrontal cortex does not do,” from Nature Neuroscience in May of 2015.
The report said that researchers, relying on a deluge of small studies with limited data sets, have “implicated the OFC in nearly every function known to cognitive neuroscience and in most neuropsychiatric diseases.” It was hard for me to understand much of this paper, but I do think I understood something.
For example, the OFC has a role to play in assigning value or significance to certain kinds of rewards and then making choices based on what is the highest reward or priority. When the OFC is damaged, then the brain can have some difficulty in tasks especially when the rules are reversed after they were learned and reinforced. It was originally thought that the OFC is involved in inhibiting learned or impulsive reward seeking behaviors, because damage to this area can result in subjects appearing to get stuck on or perseverate on the wrong choice, when the reward was switched from a previous stimulus to a new one.
There are two situations in which choices between possible rewards can arise, either de novo (when someone is first learning about this reward) and ex post facto (when someone already has experience with the rewarding stimuli). It appears that the OFC plays a very important role in reward discrimination when we are first learning about a reward, but might not so much after a reward choice is already learned. In other words, the OFC seems important to help to predict the future when the outcome is uncertain, but not when there is already a high level of confidence in the outcome. If the OFC is damaged, and you change the rules, then it has a hard time learning the new rule, and the brain defaults to the previously learned rule. The orbital frontal cortex then, is not involved in inhibiting erroneous reward seeking behavior, but in directing it to something new.
Another thing that the OFC might do is help with reward prediction errors. Once an expected reward has been encoded or learned, the OFC may help to process what to do when the reward is expected, but does not materialize. The authors of the paper I mentioned feel like it is not likely that the OFC actually generates error signals, but instead helps to calculate some kind of value for the error signals that are sent from dopamine neurons in the brainstem. This might be in the form of what is called a “credit assignment,” where the OFC can help assign credit for the error, which I think means to help assign it a proximate cause. Another way that they propose that the OFC works in the brain is as part of a larger cognitive map, where it participates in associating things like the identity of an item with some kind of value. It is queried by other regions of the brain that work together to try to predict the most likely outcomes, given the map. If the OFC is damaged, it could make access to or updates to this map impossible.
What interests me as a psychiatrist, is not really whether the OFC produces prediction error signals itself or is merely necessary to accurately process them. What I wonder is why people with OFC lesions can become impulsive, impertinent, inappropriate or violent. This suggests that the role of the OFC is inhibitory. It has been reported that it inhibits affective or impulsive responses. However, another explanation is not that it inhibits responses, but instead, that it directs someone to a more rewarding response. This is called goal-directed behavior. Without goal-directed behavior we are at the mercy of our previously learned or more basic impulses and affective states. There is then a difference between inhibition of impulses, which would merely stop a person from doing something, and replacing that impulse with a more rewarding behavior. There is increasing evidence that the OFC is more concerned with directing than with inhibiting behavior.
There are interesting experiments that might help shed some light on this. The OFC helps to process our feeling of “fullness” or satiation. Satiation may be feeling full or it could be feeling like that is enough of that particular thing… no more donuts please… even if we are not full. If we have been eating a single thing for a long time, our body will generally tell us at some point that we have had enough of that. It will devalue that particular food. If we are then presented with two foods that we like equally, one being the food that we were already eating, and the other being a new food, then most normal people will choose the new food. However, people and animals with OFC damage treat each choice as if it is equivalent in value. They don’t lack the ability to suppress or inhibit eating the same food. They lack the ability to update their goal directed behavior based on new information.
Some have labeled the OFC as the economic center of the brain, particularly adept at assessing and grading the value of different options and the costs associated with each and then passing that information forward. Remember, the OFC is not directly connected to the supplementary motor or motor cortex. However, it is communicating uni-directly with the ventral striatum, which contains the nucleus accumbens, telling it the results of the calculations if any. The OFC, then, is passing information regarding the relative value of different choices to the areas of the brain that can motivate us to do something about it.
A damaged OFC can result in a deficit of properly-valued goal-directed behavior. Conversely an overactive OFC is associated with excessive goal-directed behavior in the form of obsessive compulsive disorder. This fits more nicely with the idea that the OFC is more goal-directing than inhibitory, because if it were inhibitory, being overactive would result in more inhibition. People with OCD wish that they were able to inhibit their compulsions, but just cannot. They are, in a way, stuck in a goal-directed pathway that they cannot extricate themselves from.
Patients with behavioral variant fronto-temporal dementia have a degenerating orbitofrontal cortex, and they can also present with repetitive motor acts or vocalizations. However, in one study, the kinds of acts that generally are associated with OCD such as quote, “checking, cleaning, counting, and ordering were relatively infrequent” unquote. Instead patients demonstrated palilalia, echolalia, repetitive sounds, and tapping, pacing, picking, among other things but not in a goal directed way. Hoarding was something that people with FTD also did frequently, but although hoarding is included in the OCD chapter of the DSM, it can result from either compulsive or impulsive behaviors. Just because an act is repetitive does not make it compulsive.
In humans especially, the value of a certain goal directed or aversion avoidant behavior is highly modulated by the social context. For example, I am much more highly motivated to put on clothes when I leave the house than when I merely go downstairs. I am going to remain seated during a talk even though I feel a moderate urge to urinate because I want to avoid being seen leaving and I am interested in the topic. It is not the OFC that is directly inhibiting my urge to get up, but it is helping to weigh the different options and put them in context in order to determine which action is more desirable. Inhibition of the impulse to urinate is likely taken care of by another part of the brain, potentially the right dorsolateral prefrontal cortex. What the OFC did was to motivate me to remain seated.
How does this part of the brain that when hypoactive result in impulsive acts and when overactive result in compulsive acts make value-based decisions? When we are perceiving something that our brain can easily compare with something else, often a process called mutual inhibition kicks in. We have different populations of neurons that respond to the different stimuli and in turn try to inhibit the others. This is a simple balancing effect where the population of neurons with the most stimulation over-powers the others and the choice is made. The OFC appears to lack these kinds of neurons. The same neurons generally fire for similar choices, so this can’t be how they make decisions. It is suspected that, in order to make a decision the OFC has to do a juggling act, where it calculates or accesses an already known value, stores it in working memory, considers another value, then stores it in working memory, and so on. The OFC is obligated to change its attention back and forth between different options. This is a relatively slow process compared to mutual inhibition, but it allows for much richer data and for updating the final value based on collateral information, like risk or cost. The central or medial OFC appears more involved in coding working memory and updating probabilistic outcomes while the more lateral area appears to be doing more of the calculations.
Some suggest that the OFC is working with the ventral medial prefrontal cortex to create a cognitive map, similar to how the hippocampus has neurons that correlate with physical space. Instead of being correlated with physical space, the map here would be associations with goals and expected outcomes. It would be very costly for the brain to constantly recalculate the probabilities of reward or success every time an option is presented. This map might allow for fast checking by those dopamine neurons in the midbrain that are scanning for mismatch. No one is quite sure if this map actually exists though.
It is hard to know from lesions in humans, what the particular function of the human OFC is because few of the lesions that humans experience due to surgeries, tumors, trauma or strokes are not very precisely and exclusively related to the OFC. It could be that much of the affective changes that occurred when the OFC is damaged are related to damage to white matter tracks near it or areas within the ventromedial prefrontal cortex. What increasingly appears to be the case is that damage to this area does not release a person from inhibition, but instead releases them from complex goal-directed behavior, leaving them with less ability to weigh the choices. During compulsive behaviors, this area is overactive and potentially spending excessive amounts of time calculating and recalculating reward probabilities without satisfaction.
This far, I have discussed the orbitofrontal cortex and the dorsolateral prefront cortex. My series on the prefrontal cortex, then, is nearing an end. In the next episode, I will complete the series by discussing the medial prefrontal cortex, an area of the brain that appears to give high level control to autonomic and affect states, a lot of salience to social information, and may even help provide us with our sense of self.
Thank you for listening. I am Dr. O’Leary and this has been an episode of PsyDactive - Residency Edition.