We seem to understand the specializations of the the dorsolateral prefrontal cortex on the left better than the right side of our brain. That is because most of us do a lot more language processing on the left or dominant side. The more inferior and caudal parts of the dorsolateral PFC on the left side are more specialized for speech. The more superior parts are more involved in working memory, attention control, and task switching. The entire DLPFC is extensively connected to other cortical regions that pass information to it for consideration, and the DLPFC is extensively connected to the supplementary and motor regions that help to plan actions, and the striatum, which helps coordinate those actions. It is also intimately involved with motivation and helps us to control our emotions.
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Welcome to PsyDactic - Residency Edition. I am Dr. O’Leary, a 4th year psychiatry resident in the national capital region. Today, I am continuing a series discussing the prefrontal cortex, that blob of neurons and supporting cells just behind your forehead that has an outsized effect on your personality and your ability to consider verbal, numerical, spatial, time-sensity, social, emotional, and other types of information all at the same time. Today, I am going to get into the nitty gritty of the Dorso-lateral prefrontal cortex, which takes a lot of information from other cortical areas and instead of just being able to (for example) see that there is a baseball mit sitting in the middle of the sidewalk, explore multiple scenarios for how it likely got there, and form the words you need to tell someone else this.
I can get really confused when reading about neuroscience because so many different researchers have either different words for the same thing or slightly different definitions of the same words, or have terms that include some but not parts of other named things. Parts of the dorsolateral prefrontal cortex have been described as belonging to the frontoparietal network, the frontoparietal control network, the cognitive control network, the executive control network (or just executive network for short). I had noticed that there seemed to be different definitions for these, sometimes appearing to be used interchangeably, while at other times being referred to as separate things or for example one being a subset of the other. I asked Google Bard to explain the difference between these terms and it basically agreed with my assessment stating that the terms were often overlapping, used inconsistently, and that quote “there is no single agreed-upon definition,” unquote.
This does not stop me, however, from discussing what is connected to the various parts of the DLPFC, what it then connects to, and why this is important. I should also point out that from a gross anatomical perspective, what people often refer to as the DLPFC is much larger that what researchers who are focussing just on our executive network are referring to. Grossly there are three gyri in the brain that comprise the large anatomical version of the DLPFC. They are stationed just anterior to (or in front of) parts of the motor cortex, the supplementary and premotor cortex and the frontal eye fields. These gyri (I really love saying that word… gyri) are aptly named the superior frontal gyrus, middle frontal gyrus and inferior frontal gyrus. I love it when things are easy, but while it is easy to draw elipses around these regions, these elipses do not do a good job of distinquishing the regions functions. The middle frontal gyrus forms the center of what is often referred to.. In a very strict and limited sense… as the DLPFC, but today, I am going to include the inferior and superior gyri in my discussion.
The DLPFC cortex contains all six of the possible layers of cells in the cortex. I am not going to to into detail of each of these layers, because that would require an additional episode. I will say that some of these layers exist because they are composed of connections between different regions of the cortex, the cortex and the thalamus, and the cortex and striatal regions. The fact that all six exist her in the DLFPC means that it has maximal connectitivity to the rest of the brain. Additionally, the pyramidal neurons in the cortex are modulated heavily by serotonin and dopamine levels, which helps explain how depression and anxiety can respond to agents that inhibit the re-uptake of serotonin or dopamine. The raphe nuclei in the brainstem produce and ship serotonin to the prefrontal cortex, while the ventral tegemental area produces and delivers dopamine. Cortical neurons also receive glutamate from the mediodorsal thalamus. Glutamate is the main neurotransmitter that is used for neurotransmission between cortical neurons and other regions, but this transmission is highly modulated by serotonin and dopamine. Today, I am not focussing on the particulars of neurotransmitters, but instead on the functions of regions and their networking capabilities.
Let's start with a discussion of the inferior frontal gyrus and work our way up. The inferior frontal gyrus, as it is named is on the inferior part of the lateral surface of the prefrontal cortex. If you were to move up, you would run into the middle frontal gyrus. If you were to go down along the curve under it, you would be in the orbital frontal cortex. The inferior frontal gyrus has three main parts. There is the pars orbitalis (because it is the closest to the orbits), the pars triangularis (which is the middle triangular shaped part), and the pars opercularis. Aside from sounding like the names of an order you might give dragons in Game of Thrones or a spell in Harry Potter, the pars opercularis is also called the operculum, which means window It is call that because, if you lift it up, you can see the insular cortex under it. It is the window or operculum to the insula. Much of the pars opercularis and the pars triangularis comprise what is known as Broca’s area, a major hub of our speech interpretation and production network. Broca’s area is on the L side in about 95% of R handed folks and about 70% of left handed folks.
Broca’s area is extensively connected to a region called Wernicke’s area via the arcuate fasciculus. Wernicke’s area is located in the superior part of the temporal lobe near the temporal-parietal junction. The arcuate fasciculus is so named because in order to get from Broca’s area to the temporal lobe, it needs to arch through the parietal lobe and then back to the temporal lobe. So I don’t mislead you, I should mention that the arcuate fasciculus contains many more fibers than just the ones connecting Wernicke’s and Brocas area. Broca’s area also has connections to the anterior putamen, and the ventral anterior nucleus of the thalamus, which likely help with executing the motor aspects of speech. It was thought initially that Broca’s area was only a speech production area. It becomes active when we are preparing to speak and even when we are watching someone else speak. The pars opercularis in particular appears to coordinate a motor plan for speech production, while the pars triangularis seems to be involved more with deciding what words to use. There are connections called the frontal aslant tract (or FAT) that link Broca's area with the anterior cingulate and the presupplementary motor area that is located in the more posterior part of the superior frontal gyrus. Broca’s area also contains many mirror neurons, which likely helps us to mimic and learn speech. There is some evidence that Broca’s area also helps us interpret language, especially when sentences are complex or ambiguous. The pars opercularis in particular may be helping to understand things like the subtle changes in meaning when we intonate words differently, use a different prosody of speech, like when we say something in a sarcastic way.
I have so far neglected the pars orbitalis on the front part of the inferior frontal gyrus. I could not find a lot of information strongly supporting a particular function of this area. This region is somewhat transitional and supportive. It appears to contain more broad connectivity to other cortical regions, such as the OFC and even the occipital cortex that the triangularis or opercularis. It may help play a role in inhibition of emotional and motor responses by helping the rest of the brain consider aspects of the context of that information. In the inferior frontal gyrus in general, there appears to be a posterior to anterior gradient in the amount in interconnectivity to cortical motor regions such as the supplementary motor cortex and primary motor cortex. The opercularis is extensively connected with supplementary motor and primary motor regions. The triangularis is connected more to the supplementary motor cortex but not so much the primary motor cortex. The orbitalis lacks these motor cortex connections. However, both the orbitalis and the triangularis are connected extensively to the insula, putamen, caudate, and STN, but the opercularis is not. It appears that the opercularis is more concerned with planning out behaviors and the triagularis and orbitalis are more concerned with what to do and whether or not to do or say anything.
The L side seems more concerned with speech but what is the R side doing. You may be interested in what is hanging out in what would be Broca’s area on the R side or non-dominant side of people’s brains. It doesn’t make sense that the left hemisphere would have specialized areas and the right would not. It would almost have to by definition. It appears that what-would-be Broca’s area on the R also plays at least a minor role in understanding and producing language. There is evidence that it is more interested, though, in error detection, like trying to figure out why a person's words conflict with what they are doing; maybe if they say left, but point right. It looks for mismatch or conflict. It also contributes to maintaining attention and to salience detection, which is looking for important details. The right side may help pull cues out of language that the left side would miss because it is so focused on trying to make language. Another function of the R inferior frontal gyrus is to inhibit automatic responses. We know this from tests that have someone respond to a “go” signal, which is frequent… go, go, go, go, go… and every once in a while it is followed by a “stop” signal. The R inferior frontal gyrus in concert with the presupplementary motor cortex is more active during this task. Since there is no Broca’s area on the R frontal lobe, neither is there a Wernicke’s area on the R temporal lobe, so the connections via the R arcuate fasciculus are not specific for language processing. What the R superior temporal area corresponding to Wernicke's area does is not clear, but it may be helpful in social cognition or non-verbal memory. It was unclear to me that we knew much about this area, possibly because the kinds of tests we give people are specific for that part of the brains functional capacities.
I remember as a kid being taught that most of our brain space is unused but this is a myth. We just don’t know how to interrogate it, so we think it isn’t working. Anyway…
So here I gave a brief description of the inferior frontal gyri. The dominant (usually left) side is very concerned with producing speech and the non-dominant (usually right) side more concerned with paying attention to the environment for clues as to whether or not to do something. Both of them have important connections to the presupplementary cortex via the FAT or frontal aslant tract fibers, to the superior temporal lobe via the arcuate fasciculus, and also to the insula, basal ganglia and thalamus among other regions of the brain. That is enough to say for now abou the inferior frontal gyrus.
Lets move a little higher to the middle frontal gyrus. This is not the medial gyrus. Medial refers to the parts of the brain between the lobes. The middle frontal gyrus is on the lateral surface of the frontal lobe between the inferior and superior gyri. It may be easy to confuse these terms, medial (meaning more toward the center) and middle (meaning between other things). I want to point out here that when many people refer broadly to the DLPFC, they are actually referring to this middle gyrus specifically, because many of the functional specializations that people think of when hearing the term DLPFC come from this gyrus. When people go for transcranial magnetic stimulation therapy, or TMS, the center of this gyrus on the L side of the brains is where they are aiming to hit. That is because there is some laterality to the middle frontal gyrus, too.
Because the left middle frontal gyrus is in such close proximity to Broca’s area, it makes sense that they would talk to each other, and so the L middle gyrus is reported to be more tuned to literacy and the right, more tuned to numeracy but these are not absolute and exclusive abilities. The right side may be more mathy and the left more of a story teller, but lesions on the left side may also result in acalculia. The division is not absolute.
The middle gyrus is also very active in our working memory. Our working memory is rather fragile and can be disrupted by competing stimuli. That is why, when you really need to focus and think about something, it is best to try to find a quiet place, turn off the notifications on your phone and computer and immerse yourself in that topic. Attention or focus is a broad topic. We can discusses being able to maintain attention on a single point in space, something moving throught space, someone reading a story, a line of thought related to a single subject, like performing long division in your head. Attention may need to be focused more on the external or the internal environment. Finally, working memory is kind-of a prerequisite for attention, because if you can’t actually hold a substantial amont of information to be considered, then your attention would necessarily be more enslaved to your immediate surroundings.
The frontal eye fields are located at the caudal end of the middle frontal gyrus. They are a major hub of what has been called the Dorsal Attention Network, which focusses on what the brain thinks are salient aspects of the environment. The frontal eye fields work with regions in the superior parietal lobule (SPL), and intraparietal sulcus (IPS) to identify and track things through space. Magicians and pick-pocktets love the frontal eye fields because they processes information quickly and force people to move their eyes together toward a different spot or something moving. In neurology, they call tandem eye movements sacchades. Parts of the middle frontal gyrus may be necessary for helping us to suppress these faster parts of the brain like the frontal eye fields. Imagine being in a central downtown area in Deli, India. In order to focus, your eyes can’t be distracted by everything that moves.
In addition to the Dorsal Attention Network, there is something called the Ventral Attention Network. The ventral attention network is one of those very difficult ot define terms because it has nodes overlapping with other named networks, like the salience network, and may include parts of the temporo-parietal junction (TPJ) and the middle frontal gyrus (MFG), inferior frontal gyrus (IFG), frontal operculum, anterior insula, and anterior cingulate gyrus. I don’t want to confuse you today by adding too many words to this soup, so I won’t go into deep detail about this network. In a past episode I discussed our attention networks, so you can see that one if you interested.
To over simplify, the middle frontal gyrus helps to hold a large amount of relevant information in a ready to access form and maintain our attention where we need to have it.
Attention can be controlled in a bottom-up way, where (for example) sensory information forces the brain to put it’s attention somewhere, and in a top-down kind of way, where the brain may suppress thoughts or sensory information in order to focus on what it thinks is relevant information. It may be that the brain needs to suppress thoughts to focus on sensory information, such as when someone interrupts you when you are in deep thought but you can’t actually comprehend what they are saying, or you are fading out after listening to someone like me drone away on this podcast. It may be the other way around, where parts of the brain need to ignore that person who is talking so that you can focus on your thoughts. It may be that you need to ignore one sensation, like pain, in order to explore another one, like sexual arrousal. The middle frontal gyrus seems to be very involved in things like this. It holds a large part of our working memory (the relevant information), helps us to switch between tasks, between competing thoughts and stimuli, and to put our focus on the most important details. With regard to laterality, the right side may be more concerned with managing the switch between top-down and bottom up control, while the left side (because of it’s proximity to our language centers) may be more concerned with meaning making.
To do all of this the MFG needs to be extensively connected to other distant parts of the cortex. The white matter tracts that connect to it include the superior longitudinal fasciculus, which connects the MFG to the inferior parietal lobule, posterior temporal lobe, and lateral occipital cortex. There is also a white matter tract called the inferior fronto-occipital fasciculus, which connected the MFG to the lingual gyrus and cuneus in the occipital lobes. The MFG, then is extensively connected to areas of the brain that process the meaning of sounds and language, as well as visual and spatial information. But it doesn’t end there. The middle gyrus also has these u-shaped connections with cortical neighbors. In this way, the brain is able to keep information like the identity, location, time-relationships, social importance, symbolic meaning, literal meaning, conflicts with other information, etc all together at once. Hence, it is necessary for cognitive flexibility, the ability to consider multiple relevant options, even conflicting ones, make decisions, and plan actions.
I started with the inferior frontal gyrus and moved up to the middle frontal gyrus. Now I am going to move a little higher. The superior frontal gyrus sits just above the MFG. It appears to extend many of the functions of the MFG and may be more active when the complexity of the information that we need to consider increases. It is superior in location to the other gyri, and also gives us superior abilities to think through hard problems or find important details because it expands our working memory.
Like the middle frontal gyrus, it divides certain tasks between the L and R hemispheres. On the L or dominant hemisphere, damage to the superior frontal gyrus may impair verbal fluency, spatial processing and working memory. On the right side, it may help more to reduce motor urgency and inhibit impulsive acts. It may also help with our sense of humor, letting us know what is funny, or when to laugh. The caudal or posterior section of the SFG is comprised of the supplementary motor area, so it appears to work with this area to help prime or suppress motor activity such as laughter. The superior frontal gyrus is contiguous with the medial prefrontal cortex (that area betwee our hemispheres) and so also probably helps process information related to our identity and socially appropriate behaviors.
Although I have just treated the superior, middle, and inferior frontal gyri as different things, that was really just for convenience sake, so that I could move along the surface of the brain in those areas and talk about what they do. They are not really separate things. They are contiguous and extensively connected with other regions of the brain.
To summarize what I discussed so far, we seem to understand the specializations of the the DLPFC on the left better than the right. That is because most of us do a lot more language processing on the L side. The more inferior and caudal parts of the lateral PFC on the left side are more specialized for speech. The more superior parts are more involved in working memory, attention control, and task switching. The entire DLPFC is extensively connected to other cortical regions that pass information to it for consideration, and the DLPFC is extensively connected to the supplementary and motor regions that help to plan actions, and the striatum, which helps coordinate those actions. It is also sending information back and forth to the thalamus for more processing. Interestingly, though, the DLPFC does not get direst somatosenory information. Everything it gets has already been processed and assigned some kind of meaning before it is accessed and placed in our working memory and conscious attention.
I should stop here, because this episode is getting long, but I just can’t. One part of the discussion that is conspicuously missing it the affects of the regions of the DLPFC on our motivational and affective states. How does it help determine how we feel and why we do what we do? As a psychiatrist, this question is what really tickles my Salience Network. To understand this we need to know al little more about how the DLPFC interacts with the limbic system and the mid-brain to determine things like motivation and learning.
Some major clues to this come from studies using repetitive transcranial magnetic stimulation (or TMS) of the DLPFC. Remember when I said that the DLPFC does not get direct somatosensory information. Instead it gets already processed information and then processes it even more. The it helps us decide whether or not to do things. There is a feedback loop involved in this process where the DLPFC helps us to decide on what we should or shouldn’t do, and then it sends signals to the anterior cigulate gyrus, the nucleus accumbens and the ventral tegmental area, which are involved in planning and execution of reward seeking behaviors and our baseline levels of motivation. TMS that is directed at the DLPFC is probably working more indirectly by increasing activity in these regions, especially the nucleus accumbens which is fed dopamine projections from the ventral tegmental area. In depression, this makes a lot of sense, because the classical symptoms include anhedonia, feeling low levels of energy or motivation, and self-critical or ruminative cognitions. Talk therapies may also have their mechanism of action indirectly in a similar way, by activating the DLPFC which then helps to activate our basic reward system. I’m not saying that depression is always or mostly caused by decreased DLPFC activity or disconnection with other brain regions, but depression certainly can be treated by targeting the DLPFC with direct electromagnetic energy or by making it practice it’s ability to process speech.
Thank you for sticking with me during this rather dense topic. In the next few episodes, I plan to continue around the edges of the lateral frontal cortex to the medial prefrontal cortex and the orbitofrontal cortex, and discuss these in more detail.
I am Dr. O’Leary and this has been an episode of PsyDactic - Residency Edition.