Well, I hop this walk through gives you, just a bit of a better feel for what we're talking about when we speak about human cognition. And it will provide you a bit of a context that we can recall as we begin to dive a little bit more deeply into the associational cortices of each of the four lobes. But, before we get there I just want us to now reflect a little bit on the anatomical organization of the associational cortex and then that will be our point of departure into each lobe one at a time. Well, let's consider first of all really what we're talking about. And in case you haven't thought about it in these terms. When we consider the organization of the human brain especially the cerebral hemispheres we have to admit that even though much of the course is now past us we've really only talked about 25% of the cerebral mantle. And that's about how much of the cortex is allocated to our primary sensory and motor regions. Essentially, those areas that are highlighted in yellow here in this figure. The rest of the cerebral cortex is what we call associational cortex, so all the regions of the brain that we see in our slide that are highlighted in blue. These are brain regions that are doing the job of associating, that is, they are involved in bringing together, integrating information that's being processed, through lower to higher order divisions of our sensory and motor regions. Okay, one other point of review, I want us to recall the organization of the cortical microcircuit. as you will remember undoubtedly, I suggested that the cortical microcircuit, this cortical columnar circuit that we find replicated throughout the entire cerebral mantle preforms three principle functions. It's involved in amplifying the input which for the regions we've talked about this far largely as derived from different divisions of the the thalamus. There's also a computational function that reflects the operations of circuits, mainly in the upper layers of the cortex. and then there is a communication function as information is conveyed from one cortical column to another, or from one cortical area to another, perhaps even across the corpus callosum or the anterior commissure. Interconnecting your region of one cerebral lobe with its counterpart in the other hemisphere. Well, the cortical column as you will recall is made up of a large number of neurons. There are some neurons such as the stellate neurons and these pyramidal neurons which are excitatory. They release glutamate a nuerotransmitter and binds to kinds of glutamate receptors that we've been talking about throughout the course such as our AMPA and our NMDA receptors. Not shown here in this illustration are small intra-neurons that typically release GABA, Gamma-Aminobutyric Acid as a neurotransmitter. Those would be inhibitory intra-neurons in the adult brain Where the chloride concentrations allow for the stabilization of membrane potential below threshold, which is the definition of an inhibitory post-synaptic potential. So, these pyramidal neurons are the ones that project for considerable distance. across cortical columns from one cortical area to the other. Even from one region in one hemisphere to the corresponding region in the other hemisphere or in the case of our motor system from the motor cortex down through the brain stem and even into the spinal cord. So it's the excitatory neurons that give rise to the longest projections within the central nervous system. The smaller inhibitory inter neurons tend to give rise just to local connections within a cortical column or perhaps across a limited number of cortical columns in the nearby region within a single cortical area. Now one aspect of this cortical microcircuit that I've not yet really talked about very much is the fact that for many regions of the cerebral cortex their principle input is derived from the thalamus. All regions of the cerebral cortex are also receiving input from other parts of the cerebral cortex. And for those cortical areas that are at a higher level of processing, those cortical inputs are being sent into the middle layers of the cortex right along with the thalamus input. Well this now becomes an important distinction between the organization of let's say, a primary sensory cortex and the associational cortex. For the primary sensory cortex, the predominant source of input is from the thalamus. So, when we talk about amplification, we are mainly talking about amplification of input signals derived from the Relevant polemic nucleus. Well, when it comes to the associational cortex, we have to recognize that an additional major source of input will be other cortical areas. Now, for many of our cortical areas the bias in input is significantly shifted. In favor of these other divisions of the cerebral cortex. There remains a thalamic component to inputs for each location in the cerebral mantle. So then, for the associational cortex, it's other cortical regions that are providing the input that provides the basis. For the amplification that is happening within the cortical column well it's also this input from other regions of the cerebral cortex that is being computed and from which new cortical properties are arising. As integration and association is happening within these cortical networks. And then lastly, the communication piece likewise pertains to the operations of circuits that are giving rise to long distance projections across columns, across areas perhaps even across the hemispheres. So I'd like to show you just an overview slide that helps to put the anatomy of the associational cortex in context. So our associational cortex as I mentioned does receive inputs from the thalamus, specifically a part of the thalamus that we call the mediodorsal thalamic nucleus, as well as posterior structures including the lateral posterior nucleus and the pulvinar But these thalamic nuclei are a bit different from those that we've described in our sensory, in our motor pathways. you may remember when we first introduced the thalamus some time ago, at the start of unit three, we talked about first order and then higher order thalamic nuclei. Well the first-order thalamic nuclei would be those that provide input into our sensory cortex. The higher-order thalamic nuclei are those that we now have in view when we think of the associational cortex. So these would be thalamic nuclei which themselves are driven principally by inputs from the cortex. So these thalamic nuclei, while providing input into our association of cortex, seem to be consistent with the relay of information from lower order areas to higher order areas. Only in this case, the relay involves a loop from cortex to thalamus, now back up to Higher order or associational cortex. So, if we return to our overview image now we can understand perhaps a bit better how this thalamic input fits into the story. So, the thalamus is providing input to the associational cortex but we image that it is consistent with input from other divisions of the cerebral cortex. And that's these other divisions that are principally driving the computations that are being performed in these associational networks. So these associational networks have interactions with regions in the opposite hemisphere. Some of which are homotypic, that is they're They are the croppable anatomical unit found in the opposite cerebral hemisphere. But the projections often are a bit more widespread. They may involve non-homotypic or non corresponding areas. The sub-cortical connections of the associational cortex are similar to what we've been describing mainly focusing on our sensory and our motor systems. That is the associational cortex provides input to the striatum of the basal ganglia not so much the putamen, but as you may remember, we briefly mentioned the caudate nucleus and the nucleus accumbens as divisions of the striatum that were involved in motivating Or moving our thoughts, our cognitive faculties, our emotions. Those are the divisions of striatum that we principally have in mind here. Likewise, there are inputs that are relayed into the cerebellum from the associational cortex. Undoubtedly involving our lateral cerebeller hemispheres. this is us, fairly newly discovered aspect of cerebellar function that perhaps pertains to cognition and emotion. Still, a somewhat controversial area, but one that the anatomy would seem to bear out. So one last source of input to the associational cortex that I would highlight here are the inputs that are derived from. Our brain stem modulatory systems. And so what I have in mind here would be, for example, the neurogeneric neurons of the locus coeruleus, the serotonergic neurons of the raphe nuclei, and especially now for the prefrontal cortex the dopaminergic cells of the ventral tegmental area all of these brain stem systems have widespread projections to the cortex, and they can provide an important modulatory signal that might shape the way the circuitry of the associational cortex responds to the principle inputs that are derived from other cortical regions. In addition, there is input from these cholinergic cell that are found in a particular region of the ve, basal forebrain that we call the nucleus basalis of meynert. So these are neurons that seem to be important in maintaining attention and driving other aspects of cognition. This is the neurotransmitter system that is the target of the pharmaceutical interventions that are presently approved, at least in the United States, for treatment of mild cognitive impairment and Alzheimer's disease. specifically the cholinergic system that is Degenerating in this devastating neurological condition. one interesting approach would be to try to increase the levels of acetylcholine, even though the neurons that are producing and releasing acetylcholine are being lost to disease progression. So the interventions that are available are an attempt to either Activate the receptors for acetylcholine, the nicotenic acetylcholine receptors, that are present in the brain. Or to sustain what levels of acetylcholine may be present by inhibiting the enzymes that break down this neuro-transmittor within the brain tissue itself. Well, these interventions unfortunately don't halt the progression of the disease, but they may prove beneficial in supporting cognition, especially in the early stages of the disease when quality of life can easily go in a downward direction without the proper support that might come from multiple sources. Well, I hope this overview has given you a sense of what our discussions will be about here in unit 6 as we begin to think about the brain basis of cognition. And I hope it will give you some orientation to the tutorials that will follow where we will try to explore systematically the associational cortices of the parietal, temporal, and frontal lobes, and then eventually try to tie this together as we think about the way that brain state can be modulated, and how brain state can be integrated in the production of human emotion. So I look forward to working through unit six with you and look forward to what discussion we have on our website. So I'll see you next time, when we will consider the associational cortex in the parietal lobe.