I have no doubt that every structure in the brain influences consciousness. The specific question I ask here is, what structures are necessary? Phrased differently, are there any regions of the brain that, if injured or removed, cause a formerly conscious being to lose consciousness?
The answer below is based largely on lesion studies reviewed in “Neuropsychology of Consciousness: Some History and a Few New Trends,” by Giovanni Berlucchi and Carlo Alberto Marzi.
Importantly, in that same review they write the following:
“Attempts at localizing a hub for consciousness in the brain on the basis of the effects of brain lesions or dysfunctions that lead to unconsciousness are probably misconceived, insofar as consciousness is best seen as a global function of the brain in action.”
Is anyone home?
Lesions to the brain stem, thalamus, or large parts of the cerebral cortex all disrupt consciousness.
If an individual’s brain stem is damaged, they typically become comatose. The lights are off but someone might be inside.
If an individual’s thalamus or large parts of the cerebral cortex are damaged, they lose self awareness even though they are likely still awake. The lights are on but no one is home.
Therefore the brain stem, thalamus, and cerebral cortex are the necessary components for the generation of consciousness.
There are other lesions that disrupt self awareness in one or more aspects but do not cause a system-wide failure of consciousness. A lesion to the hippocampus can result in a fascinating consciousness deficit, where the afflicted individual has a sense of self but it is confined to the present moment. Though they understand the concept of time, they are unable to engage in mental time travel.
“In brief, amnesic patients with hippocampal lesions appear to possess a factual, semantic knowledge of a physical time, whereby present is preceded by past and followed by future, but are unable to travel in it with their mind because they cannot retrieve personal episodes from their past or imagine themselves in future episodes.” Berlucchi and Marzi.
Berlucchi and Marzi say that neurpsychology is more interested in these specific but less severe deficits in consciousness and cognition rather than the plus minus perturbations.
As you might expect, there are certain features of the brain stem, thalamus, and cortex that are essential for generating consciousness. Let’s get more specific.
Turning the lights on
In the awake, conscious brain, specialized neurons in the brain stem act as a first alert that important sensory information has been detected by our peripheral organs. Their activation can be thought of as throwing a master switch, sending energizing electrochemical signals throughout the brain.
The anatomical details of what is now called the “ascending reticular activating system” (ARAS) are still being determined in the human brain (see technical notes at the end of this post). What is clear is that there are groups of neurotransmitter specific neurons that have their cell bodies grouped into “nuclei” in the brain stem. Specifically, there are serotonergic, cholinergic, and noradrenergic nuclei, which release serotonin, acetylcholine, and noradrenaline, respectively, from their projections. The nuclei extend ascending projections upward through the thalamus and/or hypothalamus and onward into the cerebral cortex.
Incoming sensory signals can activate specific subsets of brain stem neurons, releasing a flood of neurotransmitters to rouse the brain. The intensity of the ‘hey, pay attention to this!’ signal can be a gentle nudge or a kick in the face depending on the type of sensory stimulus.
As described in “Neuropsychology of Consciousness: Some History and a Few New Trends,” many arousing systems work in parallel, each one functioning in different motivational and emotional conditions. All of them modulate activity of the thalamus and cortex, and all of them are active during waking hours and silent during sleep.
Without the brain stem, we would not be conscious. The brain stem is not sufficient to generate consciousness, but it is a necessary foundation supporting consciousness.
“The famous neurosurgeon Penfield (1978) has written that ‘to suppose that consciousness or the mind has localization is a failure to understand neurophysiology’ (page 109). Nevertheless, he has also postulated that a centrencephalic system, more or less coincident with the higher brain stem and hypothalamus, contains the nervous mechanisms ‘which are prerequisite to intellectual activity … and the initiation of the planned action of the conscious man’ (Penfield, 1954).” Berlucchi and Marzi.
Let’s get a visual sense of what the ascending reticular activating system looks like:
Here I am!
Penfield, Berlucchi and Marzi agree that consciousness is best thought of as a whole brain function. When trying to understand consciousness then, perhaps it is best to think of the dynamic processes underlying consciousness.
The brain is an organ, let’s not forget, so brain metabolism is one of the dynamic processes underlying consciousness. And the brain is just one part of a larger organism with a body, let’s not forget, so the flow of information cannot be thought of as being confined to brain alone. And the body operates as an open system, let’s not forget, so the exchange of energy and information with the environment are also important.
Maybe I am zooming out too far, or maybe not.
One of the dynamic processes within the brain that seems to be important for consciousness are reciprocal connectivity loops between the thalamus and cortex. There are excitatory thalamo-cortical projections traveling from thalamus to cortex and there are excitatory cortico-thalamic projections traveling from cortex to thalamus. There are also connectivity loops between the thalamus and other areas of the brain, but only disruption of the thalamo-cortical loops causes an individual to lose self awareness. The cerebral cortex is also highly interconnected in these reciprocal, excitatory loops.
As mentioned in “Mountains and Minds,” neurons in the human brain collectively oscillate between active and less active states. Reciprocal cortico-cortical and thalamo-cortical connectivity is believed to cause those oscillations.
“The reentrant architecture of vertebrate brains can also generate spontaneous rhythmic activity. By its very nature the mutual exchange of action potentials transmitted via reciprocal paths generates oscillatory behavior such as that observed in electrical signals recorded from functioning brains.” From “Reentry: A key mechanism for integration of brain function,” by Gerald Edelman and Joseph Gally.
What role does this reentrant/recurrent/recursive connectivity play in consciousness? This is a huge topic being actively studied, so you can be sure I will come back to this many times as I review the literature.
It seems the field of neuropsychology, like the fields of cognitive and systems neuroscience, is moving toward neural stimulation approaches to test their understanding of “consciousness” — perception, attention, memory, language, emotion, etc. I put consciousness in quotes because Berlucchi and Marzi write that the field of neuropsychology is not in the business of studying consciousness per se.
Stimulation methods such as non-invasive transcranial magnetic stimulation and invasive electrodes implanted during surgery have shown great promise in mapping the functionalities of different parts of the living human brain. For example, see these two studies using stimulation to disrupt consciousness (1, 2).
**What follows are technical notes for those who really want to nerd out.**
In addition to the brain stem nuclei I chose to focus on, there is evidence for glutamatergic, histaminergic, and peptidergic nuclei in the hypothalamus that play a role in the initiation and regulation of brain arousal. Also, a subset of the pedunculopontine nuclei are glutamatergic.
Each nuclei has a special name (ugh). I will list the nuclei that are part of the ascending reticular activating system here in case you want to learn more.
- locus coeruleus
- raphe nuclei
- laterodorsal and pedunculopontine nuclei
- tuberomammillary nucleus
- supramammillary nucleus
- orexin producing neurons in the lateral and posterior hypothalamus
Each axon tract has a special name, often named by the person doing the experiments and so inconsistent between labs (ugh ugh). The names of the tracts are unrelated to the name of the nuclei, because axons from multiple nuclei often join up and travel together along the same tract (ugh ugh ugh!). Here is a list of tracts associated with the ascending reticular activating system.
- ventral tegmental tract — rostral and caudal
- dorsal tegmental tract — lateral and medial
- dorsal longitudinal fasciculus
- medial longitudinal fasciculus
- superior cerebellar peduncle
- nigrostriatal tract
- medial forebrain tract
To get at a real understanding of human brain connectivity, labeling of specific nuclei or even neuronal subtypes within those nuclei and whole brain imaging of long-range connections is a must. Unfortunately this is very difficult with human tissue. First, until we are able to label specific neuronal subtypes in living human beings, visualizing the cell bodies and projections of neurotransmitter-specific nuclei is not possible. In addition, current human brain imaging technologies do not have adequate resolution, making it impossible to see small tracts or small branches coming off of the large fiber bundles. To get an overview of the difficulties involved, see “Neuroanatomic Connectivity of the Human Ascending Arousal System Critical to Consciousness and Its Disorders” and “Challenges and opportunities for brainstem neuroimaging with ultrahigh field MRI.”
The trickiest part is to see where the ascending axons are terminating in the brain. I don’t think anyone has yet succeeded in labeling neurotransmitter specific cell populations in the human brain stem and imaging all of the targets in other regions of the brain (please write a comment if you know otherwise!). This has been done for analogous nuclei in the rodent brain, but we should not assume that human brain anatomy will be the same. I will write more about rodent studies of the ascending reticular activating system in a future post.
Using diffusion tensor tractography imaging (DTI) or high angular resolution diffusion imaging (HARDI) tractography, scientists can visualize axon tracts in unlabeled tissue of both the living human brain and donated brains of the deceased. By doing histology in dead brains and/or using human brain atlases to (approximately) locate each nuclei, then finding axon tracts that travel from there to another predetermined target region, we can convince ourselves that we are getting a sense of where those axons are going.
DTI is an incredibly valuable tool with research and clinical applications, but it doesn’t give me the information I want in this case. It cannot differentiate between neuron subtypes or afferent and efferent axons. It can only tell where bundles of axons are, but not their directionality. Like most forms of brain imaging, DTI is both science and a technically challenging art form that takes years to master.
We know that ascending reticular activating system neurons extend ascending projections upward through the thalamus and onward into the cerebral cortex. But where exactly do they terminate there? Does the large axon bundle branch and ultimately innervate the entire cortex, as is shown in every schematic? Or is it more specific than that? What area(s) and layer(s)of the cortex do these activating neurons terminate in? What cell types do they terminate near? And is their release of neurotransmitter a diffuse flood or a highly specific communication from one neuron to another? I cannot wait until we can visualize specific neurotransmitters moving through the extracellular space. I think it will reveal so much about large scale dynamic processes in the brain.
Brain anatomy is something else. The details of brain structure have been identified at different times based on the technology available. Quite the hodgepodge of information.
This is why efforts to generate new atlases — new standards for the field — are so important. It would be incredible to have an interactive atlas that lists nuclei and their neurotransmitters, and when you click on the nuclei their projections appear so you can see how those neurons connect to other parts of the brain.
Big thanks to Yu Zhang, first author of “Diffusion Tensor Tractography of Brainstem Fibers and Its Application in Pain” and radiologist with more than 15 years of experience as a DTI tractographer, for replying to my questions about DTI and the ascending reticular activating system.