Lecture 20: Medial Frontal Lobe And The Orbitofrontal Cortex Flashcards
Anatomy of the ventromedial prefrontal cortex (vmPFC) and orbitofrontal cortex (OFC)
Brodmann areas associated with ventromedial prefrontal cortex (vmPFC) and orbitofrontal cortex (OFC)
Image B: brodmann areas in the medial part of the prefrontal cortex
Image C: Brodmann areas in the orbitofrontal cortex
Damages to the vmPFC and OFC
When there is damages to the ventral medial prefrontal cortex and orbitofrontal cortex, it usually occurs together. Because of the right anterior cerebral artery that makes a connection between both hemispheres, so when there is a lesion or rupture of this artery, there is a hemorrhage that happens in both hemispheres.
- damages often occur together and bilaterally*
Phineas Gage Case
Phineas Gage
Damage to the ventromedial prefrontal cortex and orbitofrontal cortex of the left hemisphere
- Planning:
• Capricious and vacillating in devising plans for the future and soon abandoning them for apparently more feasible ones
• Fitful (irregular and spasmodic activity)
• His plans changed a lot, he didn’t follow through on them, would abandon them - Self-regulation:
• Gross profanity
• Impatient of restraint or advice conflicting with his desires
• Was not able to inhibit his behaviour (say profanity, impatient) - Social interaction:
• Irreverent (lacking respect for others, especially those in authority)
• Lacking deference toward others (impolite)”
Patient C.D case
Damage to the ventromedial prefrontal cortex and orbitofrontal cortex of the left hemisphere. Comparable lesion to Phineas gage = same areas impacted.
• C.D.’s scores on the vast majority of neuropsychological measures were very good. Scored normally to most of the neuropsychological evaluations but he had impairment in:
• Impairments:
• Multilevel executive functions = increased error rates
• Memory tasks (why?…)
• Sacrifice accuracy for speed
• Adopt liberal response strategies
• Implicating problems with cognitive inflexibility, impulsivity and disinhibition (can impact other types of cognitive tasks.
• (because it is associated with) inability to change behavior to get different/more desirable results. You do whatever pleases you , whatever is easier at/ feels right at the moment.
These regions are not specifically involved in memory or cognitive function. The reason why he could not perform, was because he was unable to inhibit his behaviour, he was impulsive and wanted to react quickly. He adopted liberal response strategies. So it is really his decision making that was impacted, it was not his memory, or executive function per se, to was his decision making. But, it was reflected on other tasks.
Damage to the vmPFC and OFC
Etiology - usually due to:
• Rupture of aneurysms located in the anterior cerebral or anterior communicating arteries -> bilateral lesion
• Surgical removal of tumors (e.g. orbitofrontal meningiomas)
• Headinjury->bilateraldamage
Behavior
Emotional and behavioral changes/ maladaptive behavior:
• Impaired ability to make rational decisions in personal and social domains
• Impaired processing of emotion (we cannot process the emotion of others or our own emotions)
Few, if any, cognitive deficits:
• Normal ability to solve abstract problems and perform calculations
• Normal ability to recall appropriate knowledge and pay attention to it
• Normal performance on tests of the executive (frontal lobe) function (when we are able to dissociate between decision making and executive function, then we can see that they are able to perform well on executive tasks.
Study of patients with vmPFC and OFC lesions
- remember this kind of damage usually occurs together.
“Damage to the ventromedial sector disrupts social behavior profoundly. Previously well-adapted individuals become unable to observe social conventions and unable to decide advantageously on matters pertaining to their own lives.
Remarkably, the patient’s intellectual abilities are generally well preserved, in the sense that they have normal learning and memory, language and attention, and they even perform normally on many so-called executive function tests.” - Bechara
• Patients with damage to the vmPFC and OFC:
• Emotional changes and maladaptive behaviour
• unable to observe social conventions, unable to decide advantageously on matters pertaining to their own lives.
• Few cognitive deficits
• The syndrome suffered by these patients has been documented as ‘acquired sociopathy’, reflecting the fact that the personality and decision-making effects of damage to this region resemble a milder form of those seen in sociopathy (Damasio et al., 1990, 1991; Tranel, 1994).
- sociopaths are not able to understand the consequences of their actions. They do not value the future in the making of their decisions. Focussing on the immediate reward of their actions. Criteria they are using to make decisions is only based on the present moment.
The OFC is organized along two axes..
• Neuroimaging studies suggest that OFC is organized along two axes:
• A mediolateral axis
• positive outcomes (e.g., fruit juice) are encoded medially and negative outcomes (e.g., a puff of air) are encoded laterally —> negative or positive outcomes will activate different regions in the brain.
• Anterior-posterior axis
• concrete outcomes (e.g., with food) are encoded more posteriorly than abstract outcomes (e.g., with money)
How does the lateral part and medial part contribute to decision making?
Study looked at the behaviour of monkeys when they had a lesion to the lateral orbital frontal cortex and to medial orbital frontal cortex.
Task: the monkey had three types of stimuli presented to them. One was the best choice, the best choice was associated with the biggest reward. The two other choices were associated with other probabilities of reward. There was variability across the trials so they really needed to learn how each stimulus was associated with a reward.
Alternative hypothesis based on selective lesions in monkeys:
• lOFC→credit assignment. We assign a credit value to each type of stimulus. This is independent of the animal decision because they learn it.
• mOFC→value comparisons → important for making the correct decision
They had the first reward which was the best, but the second choice they really decreased the value. The second choice was associated with 65% of reward. Sometimes it was associated with no reward at all. Sometimes it was associated with 33% (varying probability of stimulus #2).
Image:
- the first 3 graphs show the reward probability for each trial
- the second row of graphs shows in green the proportion of choosing V1 before having a lesion to the lateral orbital frontal cortex or medial frontal cortex. More you have trials, more you learn. THis shows that the monkey is learning the credit assignment of each option. In blue, we have the proportion of choosing V1 after a lesion to the MOFC. Looking at this graph, you can conclude that the monkeys do not learn after a lesion to the MOFC. They do not learn because they are not able to compare value V1 and value V2 when they are so similar. Therefore, the middle OFC is associated with value comparisons.
On the other hand,when we look at monkeys with lesions to the lOFC, we see that they are able to learn when V2 is high.
Looking at the case where there is a big difference between V1 and V2, the monkeys are able to learn with middle OFC. When we look at G, V2 is associated with a lot of reward so they are associating both V1 and V2 with a lot of credit / high reward. When they have a lesion to the IOFC (in case I) they are learning more slowly. They are assigning credit more slowly. This is the case because V2 is associated with no reward they are not able to make the difference between V2 and V3 because they are similar probability. They are not able to distinguish between all three.
Conclusion:
- lesion to mOFC = when V1 and V2 are similar cannot learn difference. When big difference can learn
- lesion to lOFC = when V2 is high they can learn. When V2 similar to v3 cannot make difference between the two.
The OFC and the Reward system
• Directly integrates sensory (e.g., primary olfactory, gustatory) and reward information. Part of our reward system is associated with sensory info.
• Patient damage demonstrates many intact cognitive abilities (e.g., memory, language) with a loss in good decision making.
• OFC dysfunction part of many neuropsychiatric disorders (e.g., OCD, pathological gambling, eating disorders) where impaired choice behaviour is a common feature
When we look at lesion in the OFC or grey matter in the OFC, we can see that people with OCD, pathological gambling, eating disorders, they will have reduced grey matter inn the OFC.
The lateral OFC and medial OFC are connected to the thalamus and other subcortical structures (and the midbrain which is associated with the reward systems).
When we understand the brain, we can look at different neuropsychiatric disorders and we can understand them better:
- Gambling is associated with poor decisions based in incorrect reward credit assignment and value of choice option.
- Everyone makes decisions based on our personal and subjective opinion. The OFC is very important in that kind of decision
The OFC and the Reward System Study
Monkeys were given 2 choices: water or juice
• Seminal study in monkeys by Padoa- Schioppa et al. 2006 – made choices based on different volumes of different liquid reward:
➢ Thirsty monkeys prefer juice > water, so if given equal volumes of both, chooses juice
➢ However, if increase volume of water, monkey will start to choose water more
• At some point, the volume of water will compensate for its less desirable taste exactly, and the monkey will be indifferent between the two choices: if the monkey is equally likely to choose four drops of water or one drop of fruit juice, we know that the monkey considers the taste of juice four times more valuable than water.
Image: panel B: the monkey had offer A (juice) or offer B (water). Proportion of juice to water on X-axis. Basing his decision on the economy.
- we can see that there is a learning curve to this. When we come back with a 3:1 ratio, the monkey now chooses the water because he learned to do economy.
*Always basing our decision on reward vs economic value.
Is it the neurons in the OFC that is associated with the reward system behaviour?
• Padoa-Schioppa and colleagues made recordings during the decision process = the firing rate of OFC neurons correlated with the value of the liquids on offer.
➢For example, a neuron would show a higher firing rate when the monkey was choosing one drop of juice compared with when he was choosing one drop of water. However, the neuron’s firing rate would be the same when the monkey was choosing one drop of juice compared with when he was choosing four drops of water. This is how the scientist knew that one drop of juice is equivalent to four drops of water for the monkey.
• Seems to be based on the monkey’s valuation of the reward
Look at how much a neuron is firing depending on the decision that was made.
Another stud: OFC and reward system
This study, the animal had to choose between different pictures associated with different reward probability (the reward was juice). The neurons in the OFC was modulated by the probability of receiving a reward and the amount of juice that the monkey received. Each picture was associated with a reward probability.
• higher payoffs is associated with higher firing of the neurons in the OS.
• Multiple factors such as reward probability, amount of reward, and cost to get the reward are integrated by OFC neurons to determine value (multiple factors affect our decision making)
• Affects decision making→ value of an expected outcome
• It is hypothesized that OFC patients are forced to make decisions more or less at random because they lack the signals as to the value of the expected outcomes that might result from different possible choices.
A patient with lesions to the OFC cannot learn this kind of reward, probability or payoff, and they will not be able to make decisions based on the value of expected outcomes. This is because the lack the signals in these brain areas.
MAIN FUNCTION OF OFC
• Credit assignment - we assign value to each component that affects our learning
•Value comparisons that will affect our decision making
•Reward probability (trade off, economy)
The functional organization of the vmPFC
• Brodmann map
• Areas 24, 25, 32, 14, 11, and 10 compose the vmPFC.
• To facilitate comparisons across species, newer specification further outlines medial, rostral, and caudal zones of area 14 (14m, 14r, 14c - area 14 separated in medial, rostral and caudal).
•if there is more specification in the neuroanatomy of the vmPFC in humans then this means that the decision making in humans is more complex. It is based on more information. VmPFC is very important for the social emotional aspect of decision making,
• Localization
• vmPFC and immediately adjacent areas in ACC (in limbic system = emotional processing) and OFC (associated with value probability, credit assignment) important for processing complex social stimuli.
• Function
• Involved in the emotional aspects of decision making, learning and social behavior
The different parts in the vmPFC
Different parts of the vmPFC associated with social, emotion and decision making. All of these local behaviours are localized in proximity because they interact always together with the reward system.
• Functional distinctions of emotional, social, and valuation processes
• Map the structural distinctions that have been characterized in
vmPFC.
• Experience of rewards (anterior areas of vmPFC)
• Decision between rewards (posterior areas of vmPFC)
• Posterior VMPFC and negative affect: depression and anxiety
• Perigenual vmPFC and positive affect – e.g., reward value (area 14)
• Connections with limbic and subcortical structures
• hypothalamus, dorsomedial thalamic nucleus, septal region, amygdala, hippocampus, striatum
• Involved in control of basic biological functions, emotional processing, etc. Will be associated with our primitive emotions.
Remote memory
Long term memory does not need the hippocampus anymore. It is because the hippocampus, at first when it needs to consolidate memory, it will get the information (it is crucial to consolidate new information). Then the hippocampus who has the memory stocked will talk with other cortical regions and will delegate them to keep the memory stocked. So the hippocampus will communicate with other regions, until these regions talk together. So that the cortical regions will communicate with the prefrontal cortex.
If we lose the PFC, we willl be able to retrieve this memory it will just be altered.
Why do we need the connection with the PFC?
To learn - we want to make sure that if we make a mistake that we will not repeat it. Or if it is good we want to remember so that we can do it again
Drug addiction
Drug addiction will activate the reward system in the ventromedial prefrontal cortex and this is why people will use drugs because the reward will be so important. But with time, the prefrontal cortex will be reduces, the grey matter will be reduced, the connectivity with other regions will decrease and then you will need more drugs because the reward is less important
Mood and anxiety disorders
People with anxiety disorders and mood disorders will have less connectivity between the prefrontal cortex and other regions. So they will not be able to activate the reward system in an optimal way in order to look at the positive outcome of things.It is not only in the OFC, its also in the ACC and lPFC, everything can be effected. F
• Different processes in different frontal regions:
➢The role of reward in OFC is linked to the processes of evaluation, in ACC it guides learning and action selection, and in LPFC it helps to control attentional and executive processes.
• Understanding these different roles has implications for the diagnosis and treatment of psychiatric illnesses.
SUMMARY of OFC’s and vmPFC’s functions: Reward, social behavior, personality, decision making, judgment, remote memory, emotions and psychiatric disorders
