Scarecrow: I haven't got a brain... only straw.
Dorothy: How can you talk if you haven't got a brain?
Scarecrow: I don't know... But some people without brains do an awful lot of talking... don't they?
Dorothy: Yes, I guess you're right.
―L. Frank Baum
Source[Turci et al., 2018] Ch4al and Ch4am refer to groups of cholinergic neurons in NBM that send projections to the cortex.
Have you ever wondered what precisely makes the brain tick? Or What keeps the constantly stream of energy welling up within our bodies when we are alert and awake? What exactly is the brain’s engine room? And what is producing the momentum which makes everything else go?
This is a very vital question, because the brain is always in constant motion. There is often an elementary level of brainwave activity, which means that "neurons", even in a state of complete rest, are oscillating.
This means that the brain is constantly doing something. The brain is not like a computer, therefore, It never truly turns off or shuts down, unless something is very critically wrong.
Currently, Researchers reports that the deepest, and the oldest part of the brain sets the level of activation for the newest part of the brain, "the cerebral cortex". Understanding how the brain is designed paves the way for unprecedented approaches to disorders such as Alzheimer's disease and depression.
Understanding the essentials that keeps the brain going, and what provides the energy which drives the whole system, is of obvious value for understanding health and illness and for developing tools to alter brain activity in more predictable ways. People talk about the "default mode network", which produces what our state of mind is like when we are awake and at rest, what thoughts drift in and out and what the emotional tone is like, etc. What precisely keeps the DMN going, from down below?
Comprehending the areas of the surface cortex that can inhibit excessive emotion generated by the hard-to-reach limbic system makes it possible to use a strong pulsing magnetic field to buff up cortical activity in a specific area and makes it easier for people with depression to change their mood for the better and deal with repetitive, negative thoughts. This is called "Transcranial Magnetic Stimulation" (TMS) , and is now considered a standard psychiatric treatment.
The deep, old parts of the brain, situated just above the spinal column and in the middle of the brain, generally known as the basal forebrain, are evolutionarily ancient structures shared by humans with other animals, with the same basic brain blueprint.
The basal forebrain is entwined in basic brain processes, passing bundles of neurons called “projections” to many other brain areas, including the whole cortex. The cortex is the outermost surface of the brain.
In humans we've add the “neocortex”, a wafer-thin film of additional tissue which enhances our mental function in comparison with other animals (hence, the world). The basal forebrain also sends projections to subcortical (“under the cortex”) areas of the brain, including the amygdala, involved with strong emotions including fear, and the hippocampus, involved with memory and context, and other major areas.
Signals in the brain are passed in various ways, majorly electrically and chemically. These chemicals are myriad, complex brew of little molecules, short proteins “neuropeptides” and a variety of hormonal molecules, often generally referred to as “neurotransmitters”. Many of these molecules are shared by the nervous, endocrine and immunological systems, while some are localized within the brain.
When it comes to the basal forebrain, the projections it sends are associated with several major neurotransmitters. They are associated with different general effects, such as glutamate and excitation, GABA (gamma-aminobutyric acid) and inhibition, and acetylcholine (abbreviated "ACh" and referred to as "cholinergic") with important regulatory effects. ACh, for example can decrease activity in the cortex by slowing down synchronization of neurons, and is implicated in Alzheimer’s Disease. Cholinergic projections from parts of the basal forebrain strongly impact level of arousal (Example: alertness and drowsiness) and thinking.
Researchers have been interested in a particular part of the basal forebrain, called the “Nucleus Basalis of Meynert” (NBM), as a potential driver of resting state brain networks such as the DMN. While brain networks creates local activity via interactions among the parts making up those networks, they are also dependent upon the background global level of brain activity to keep afloat. It’s a little bit like keeping your muscles slightly tensed, but loose enough to move quickly when waiting for a tennis serve or a ball to come over the plate; there’s a baseline tone upon which responsiveness is optimized, creating a nimble ("complexly adaptive") system.
Does the NBM play a role in pushing up this base level of global brain tone? In order to investigate this question, Turchi and colleagues (2018) inactivated and reactivated tiny areas of the NBM in Macaques monkeys, measuring FMRI (functional magnetic resonance imaging) of their cerebral cortex. Because the NBM has specific sub-regions, separated by mere millimeters, researchers hoped to learn how specific the NBM was at driving activity in the cortex. They found that when they switched these deep forebrain areas on and off, very selective areas of the cortex also switched on and off. This diagram shows how precise the bottom-up influence is; the purple and green areas of the cortex correspond to tiny clusters of cell activity in the forebrain:
While there is some overlap, and perhaps some areas which are not covered by these parts of the NBM, this study shows evidence of a "one-to-one" mapping of areas of the basal forebrain, and evolutionarily ancient area of the brain, onto the more recently developed cerebral cortex. These areas all have specific functions, and are embedded as part of various higher-order brain networks. The forebrain, leading from behind as it were, sets the baseline levels of activation for whatever specific brain regions are doing.
What about brain networks? Does the forebrain selectively influence these key functional networks, including the aforementioned default mode network, and others like the salience network which determines what we pick up on and what we ignore around us, and the executive control network which guides
motivation and attention and helps regulate emotional states? Prior research has shown that the amygdala (often thought of only for fear but involved intense positive and negative experiences) switches activity in specific brain networks, so what about the NBM?
As it turns out, in this study scientists did not see a connection between specific network activity and switching areas in the forebrain. While overall tone is influenced via cortical and subcortical areas projected to by the forebrain, so far a specific connection from the forebrain onto common networks has not been identified. Yet, it may be via regions which have not yet been tested. This is important research from a basic neuroscience perspective, as well as from clinical and neuroengineering perspectives. Understanding that areas such as the forebrain, highly conserved across species, set the activation tone for the cerebral cortex moves basic knowledge a significant step along. It is likely, but needs to be studied, that what is observed in primates is similar to what is happening in us humans. And of course, there are many brain areas which project onto and influence activity in the forebrain itself...
For conditions of disordered arousal, such as dementia, and other neuropsychiatric conditions, or for understanding how medical illnesses may affect the brain as well, mapping out the function of the forebrain is critical for developing therapeutic targets. For example, it could be possible to insert a brain-stimulating electrode into key areas of the forebrain to amp up global cortical activity in patients with decreased function, or even to use non-invasive neuromodulation techniques such as TDCS (transcranial direct current stim) to reach deeper brain areas.
Techiques like deep brain stimulation are already being used to treat Parkinson's Disease and severe Major Depressive Disorder, and severe Obsessive Compulsive Disorder can be alleviated by destroying tiny amounts of brain in very specific areas. If we know how the brain is engineered, we can develop and test targeted neuromodulation approaches based on that understanding. Future research is being conducted to continue to refine our understanding of how the brain works, how networks of the brain function in relation to anatomical areas and physiological processes, and how basic neuroscience can translate into clinical applications, and possibly human performance enhancement.
References
Turchi et al., The Basal Forebrain Regulates Global Resting-State fMRI Fluctuations, Neuron (2018), https://doi.org/ 10.1016/j.neuron.2018.01.032
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