Welcome again to unit six of Medical Nueroscience, where we have been discussing the associational cortex of the cerebral hemispheres. And in this session we turn our attention to the frontal lobe. And I'd like to speak with you about the associational cortex that we find in this very large and very important part of the human brain. Our topic today pertains to the two core concepts in the field that have been especially salient for unit six on complex brain functions. It's to the integrated action of the associational cortex, that intelligence arises in the brain. Especially in our brain where associational cortices are so well formed and well evolved. And this intelligence allows our brain to reason, to plan and to solve complex problems. That's not to say that other brains aren't capable of that, indeed, in insect colonies, even with their ganglia. It's hard to call what they have a brain, but one may choose to do so. But even in the central nervous system of insects, we see some capacity for each of these dimensions of cognition. But certainly for us, much of what we associate with the intelligence of our species is attributable to the integrated action of our association cortices. And it's our human brain that endows us with the curiosity that, drives us to, explore our world. And even pursue studies of things such as medical neuroscience. My Learning Objective for you in this tutorial is to discuss the major functions that are localized to the associational cortex in the frontal lobe. So this tutorial, we're going to turn our attention to the frontal lobe. So I'll just remind you that the Frontal Lobe is bounded posteriorly by the central sulcus. And here we see the central sulcus continuing into the medial face of the hemisphere in the paracentral lobule. The frontal lobe is bounded inferiorly by the lateral fissure, which is also known as the Sylvian fissure separating the frontal lobe from the temporal lobe. Now when we look at the frontal lobe we realize that there are really two major cortical territories that we find in the frontal. here would be our central sulcus, dividing the frontal lobe from the parietal lobe. And as you know, at the posterior aspect of the frontal lobe we have our motor cortex. So anatomically, that's localized to the paracentral gyri. and then to the posterior part of the superior middle and inferior front gyri that harbor the premotor mosaic in the two hemispheres. So the posterior part of the frontal lobe is essentially our motor cortex. So, when we talk about the associational cortex of the frontal lobe, basically what we're describing is all this cortex, that sits interior to the motor cortex. And that would of course include the cortex that we find on the medial face of the hemisphere. Now we do have an unusual term that we use to talk about this part of the frontal associational network. Work, we call this the Prefrontal Cortex. So you may be wondering, well that's an odd word. Prefrontal what does that mean? Well Prefrontal essentially means cortex that is anterior or before the motor cortex. So for our purposes, the prefrontal cortex can be localized anatomically as the anterior two thirds of the superior, middle and inferior frontal gyri. Remember our three fingers here on the dorsal-lateral aspect of the cerebral cortex. So roughly where my three fingers are, that would be the prefrontal cortex as seen from this dorsolateral view. And then, from the medial view, the prefrontal cortex would include the cortex of the superior frontal gyrus and the cingulate gyrus. As they wrap around into the medial part of the orbital cortex of the brain, including this gyrus rectus here. Right along the midline on the ventral aspect of the frontal lobe and including an interesting little region right here called the subcallosal area. Right underneath the [UNKNOWN] of the corpus callosum. Now the posterior boundary of this prefrontal cortex would be, again, roughly. About two thirds of the way along the length of the cingulate and superior frontal gyri. We would recognize the premotor cortex sitting just a few centimeters in front of our paracentral lobule. So once we get roughly anterior to about this location, we're dealing with our prefrontal cortex now as we see it on the video phase of the hemisphere. Now we also of course include the orbital surface of the brain. And our orbital cortex is part of our prefrontal associational network of the frontal lobe. All the way back to where the cortex of the frontal lobe gives way to the basal forebrain region in the hypothalamus. Now for our purposes, I'd like to further subdivide the prefrontal cortex into two majors sectors. So, the dorsolateral prefrontal cortex. Is where our executive functions are governed. And by executive functions, what we really mean are those functions that are associated with planning. Planning behavior based on the integration of sensory signals with other sources of information that would include our memory, our emotion, our interoceptive signals. And the integration of these signals gives rise to plans for motor action. These functions are exemplified in the phenomenon that we call working memory. You'll recall that we can think about the temporal dimension of memory. And realize that there is a period of time from maybe seconds to minutes. Where it's possible to maintain in consciousness some goal that can motivate our behavior. So this is what we have in mind by working memory. Imagine for example that you're looking for a lost object. Perhaps it's a set of keys, or perhaps it is a coin, or some other possession that is of value to you that motivates your desire to, to seek it out. That process of search, wherever you may be, in your home, in a yard, in a public place. That search is being motivated by the maintenance in your consciousness of that object, that goal that's motivating your behavior. So this is the concept of working memory. Yes, it's dependent on your medial, temporal lobe memory system. But really, what's going on is, is this object is now being maintained in awareness in the circuitry of your dorsolateral prefrontal cortex. So that it can guide the appropriate search behavior. Well, we've studied this in various ways in animal subjects and human patients. And I'd like to share with you some really seminal work done by Patricia Goldman-Rakic and her colleagues at Yale University. In the late 80s and into the 90s. this work really began to develop a neurophysiological model for working memory. And what Dr Goldman-Rekic and her colleagues did was to record from the cortex that is found in the banks of the principal sulcus. And the Rhesus monkey brain, so this would be roughly equivalent to recording from the inferior aspect of the superior frontal gyrus in the human brain. And what they're able to demonstrate with a very intriguing behavioral paradigm. Is that there are neurons whose firing activities seem to represent the goal of the behavior that's held in working memory. So here's the paradigm, an animal model, a rhesus monkey, is, observing the placement of a morsel of food in one of these two wells that are within arm's reach. So the monkey's aware of of in which well the food was placed. So now a delay is interposed between the observation, the sensory information coming into the animal, and the ability to execute the appropriate motor behavior. In this case, a visually guided reach to retrieve the food reward. So this delay is imposed by a screen that's lowered. For some period of time, typically some number of seconds. So after some period of delay, the screen is now raised, and this monkey is now free to uncover the well of choice and retrieve the food morsel. So there's this period of time, this delay period. Where the working memory of the animal is exercised. The goal of the pending behavior is held online until that time when that behavior can be executed. In this case, a visually guided reach. Well, well what Dr Rakic was able to demonstrate Is that there are neurons in this dorsal lateral prefrontal associational network. Whose firing rates are modulated by this delay. So here's recordings from a single neuron in this part of the brain. And what we see is that the firing rate is elevated during this time of delay. So the delay is indicated by this region here, that is shaded red in the background. And so when there is a food morsel that is loaded into the well and the monkey can see that we see that the activity of this neuron rises. During the delay period and, immediately following the delay, when the behavior to be executed, theres a sharp fall off in activity for this cell. Suggesting that what this neuron is encoding, is the information that it is going to guide the execution of the behavior when its possible to do so. In other trials, when the food was not introduced simply lowering the screen and after delay raising the screen. Didn't really seem to modulate this neuron's firing much at all. So this neuron doesn't necessarily seem to be responsive to the sensory elements of the stimulus. It's not necessarily encoding the dynamics of the movement, per say. What it's doing is it's holding online information that is motivating the behavior. Well, why should this be important? Well I think that much of our daily lives are actually guided by working memory tasks, such as this one. Well we may not be often retrieving a food reward after an imposed delay, but we're constantly planning for the future. And those plans be they short term or long term, are predicated upon being able to represent the goal that's motivating our actions. Well the prefrontal cortex is very much involved in organizing behavior for future plans, both short and long term. And one should not be surprised, then, that this is a part of the brain that's relatively slow to develop. In fact, the prefrontal associational cortex is among the last portions of the brain to, to really fully achieve, adult volumes for both gray matter and white matter. And, also, the adult degree of milanation that gives our white matter pathways their structural integrity. And, and presumably, therefore, the efficiency by which signals can propagate and that information can be processed. Now once this dorsal lateral associational network is fully mature, it plays an important role in making use of prior experience, prior information, to guide subsequent behavior. So, working memory is one example of this, but there are also other real world examples that are worth some consideration. So, imagine a developing child going through adolescent years and learning about the rules that govern our social relations, our culture, our society. And certain behaviors are usually considered to be appropriate and acceptable and, and others are not. And this developing child adolescent is learning to integrate those rules and to moderate behavior. Such that appropriate behaviors are shaped by these social norms that we acquire, typically in the first couple of decades of life. So this dorsal lateral prefrontal cortex as it turns out also has a very important role in moderating or suppressing behaviors. That would otherwise be considered to be inappropriate. I think, more generally speaking, we can recognize the importance of this capacity to help us navigate our complex dynamic lives in the real world. Where sometimes the contingencies for reward and punishment might be changing.
