The Navy SEAL’s Acetylcholine

Last night President Obama announced that Osama Bin Laden was dead.  And this morning we heard that the Navy SEALs and CIA commandos who killed him had shot him in the head, just above his eye, which is to say, the orbitofrontal cortex (orbit refers to the socket holding the eye, frontal means frontal.  The orbitofrontal cortex, which plays a key role in emotion regulation and decision making, is thus the “front part of the brain over the eye.”)

Which raises a question for all of us marveling at how well this mission resolved itself: how, with all the sound and fury unfolding around them, in an environment they had never been in before – in the dark, in a suburb of Pakistan, against a target doubtless eager to avoid injury, and with the awesome weight on his shoulders of of taking perhaps the most important single shot in American history since 1776 – the Navy SEAL who shot him stayed so focused as to take a perfect shot?

The question gives us a chance to focus in on one of the “big seven” neurotransmitters in the brain: acetylcholine.  Because the best way to think of acetylcholine is as the attentional filter of the brain.  It keeps noise out, and lets signal in.  And for whoever shot Bin Laden, their focus was lasered in on his face.  Once their brain identified him and saw he wasn’t surrendering (though apparently it was a kill mission from the start), they shot.  If they hadn’t been filtering out irrelevant details, this would not have been possible.

Acetylcholine 101: Acetylcholine is a Filter

In a nutshell, acetylcholine increases mental focus in the presence of distractors – which is to say – on whatever you are sensing.  As you read this, if you notice the feel of your hands on the book, or your rear end against your seat, or hear the sound of your own breathing, or see something moving out of the corner of your eye – acetylcholine is doing its duty.  It is amplifying your attention to whatever interests you, and leaving everything else in the attentional dark.

Acetylcholine 201: Signal and Noise

If you have ever needed to fall asleep, but found yourself instead focusing on some sound in the room, or a particular thought in your head, you may have wished that you could ‘turn off’ your attention. Perhaps your mind turned to the vague memory that ‘white noise’ machines can help people fall asleep by ‘drowning out’ unwanted noises.  White noise absorbs the creak of a board, the honk of a car horn, or even your own breathing.

One way of conceptualizing what you’ve noticed in contrasting your acute awareness of specific thoughts or perceptions, on the one hand, and the nonspecific, oceanic peace of white noise is by way of analogy. Attention is like the resolution of a digital camera.  It can be highly focused and fine grained, aware of every minute detail of some stimulus.  Or it can have what photographers call (and often actively seek out) ‘bokeh’, in which smooth, vaseline-like vagueness overwhelms detail.

In information processing theory, focus or detail or specific sensations can be conceived of as ‘signal,’ while unfocused, smooth, vague white noise can be conceived of as ‘noise’ meaning the lack of any clear signal.

As the sleep example made clear, and as all photographers know, it can be very useful to have control over how much signal and how much noise you are exposed to; each is useful under certain circumstances. In fact the reason that many professional photographers don’t like point-and-shoot cameras is that the small lenses make noise very hard to achieve – everything is in focus, which often detracts from the artistry of a photograph.

All this said, it is not surprising that the brain has an attentional signal-to-noise control knob, not unlike the aperture ring on a cameraAcetylcholine is, most generally, a tool for increasing the signal to noise ratio of incoming sensory information to cortical neurons (Sarter et al).

Acetylcholine 301: Sensory Resolution

Consider three facts: medical, photographic, and physical.

First, it is a medical fact that too much acetylcholine turns to pinpoints the pupils of your eyes, as though you were squinting at the sun, and too little acetylcholine makes them as wide as saucers.

Second, it is a photographic fact that the aperture ring on an SLR camera makes the hole through which light enters the lens small or large.

And finally, it is a physical fact that the size of a the hole behind the lens of a camera – whether caused by the pupil of the eye or the aperture ring of an SLR – determines how much of the picture is in focus.  Small holes bring EVERYTHING into focus – the person 2 feet away, the doorway 4 feet away, the tree 100 feet away, the mountains the far distance.  Everything is equally clear; the ‘depth of field’ is infinite.  On the contrary, very large holes make almost everything out of focus.  If you focus the lens of the camera very carefully, perhaps the person 2 feet away will be in focus; but the doorway? the tree? the mountains? Pure blur.

These three facts form the metaphor for usefully thinking about the role of acetylcholine in the brain, which in a nutshell is to determine that what is important, at the present moment, is in attentional focus, but what is not remains blurry and irrelevant.  The concept of attentional focus here is important. It describes your ability to hear only what the person across the room at the cocktail is saying about you, rather than listening to anyone else’s converation; your ability to see only your child in a crowd of kids at the zoo; your ability to feel only the slight brush of the hand of the girl you’ve had a crush on all school year as she sits next to you on the bus, and not the bumps from your other classmates or the hard plastic seat on which you sit. It’s what allows you to put a bite of Indian food in your mouth – chock full of a hundred different ingredients – and say ‘I think there’s too much cumin.’

Acetylcholine and Basal Forebrain Effect on PFC Executive Attention (Sarter et al)
Acetylcholine and Basal Forebrain Effect on PFC Executive Attention (Sarter et al)

Increasing Sensory ‘Resolution’

Imagine if they invented a camera that, when it detected a person’s face, physically added pixels to the part of the photo sensor in order to increase the resolution of the face without changing the number of pixels anywhere else – for example, devoted to the chair the person was sitting on.  As a result, far more detail would be available about the person’s face than the chair.

This is, in a sense, what acetylcholine does. Adding Ach to specific brain regions that process sensory information literally increases the number of neurons – and the total size the brain area – that responds to a given sensory stimulus for a variety of types of sense, including touch and sound, for example (Penschuck et al, Mercado et al, Kilgard et al).  This is equivalent to, say, increasing the number of pixels in a part of a digital-camera chip that are devoted to a person’s face.

Imagine you are sitting in a restaurant with a friend, talking about a movie you’d just seen, and your friend has just launched into a predictable critique of the movie as  having a cliched ending.  All of a sudden, out of the corner of your eye, you see a famous Hollywood star eating at the table next to you, talking animatedly. Odds are, you are going to ‘tune out’ what your friend is saying in order to devote more attention to the star – even though you know it’s rude.

This is an important point about focus, including attentional focus: you tune some things out at the same time as you tune others in. But this ‘spotlight of attention’ doesn’t happen as a matter of course, like gravity – it is an active product of the brain, and relies upon a neural mechanism.  Ach plays a role in this (Kimura et al  It appears to simultaneously dampen associational input that you already know into a cortical regions (via muscarinic receptors), while amplifying new information that you receive through thalamocortical input (via nicotonic receptors) (Hasselmo et al).

There is debate over whether there may be a second benefit of Acetylcholine’s effect on focus – the potentiation not only of real-time focus, but of memory of the event.  Weinberger as argued for the existence of this benefit (Weinberger et al), but experimental evidence has been paltry (Roberts et al).  Overall, it seems that Ach’s effects are much more on behalf of here-and-now attention than for learning (Salter et al).

Point and Shoot Cameras

There are some cameras that decide themselves what should be in focus based on what they are looking at – new events, emotional events, or stressful stimuli all are ‘more important’ than well known, nonemotional, non-stressfu stimuli, and are ‘automatically’ focused upon.  We are not far from the day, for example, when a camera focuses on a new face in an old crowd, or picks out fire or guns or rapidly moving objects, and automatically focuses on them.

In science this is called ‘stimulus driven’ focus because the focus is determined – or driven, in the sense of a rider driving his horses – by events in the outside world, the stimulus.  The equivalent happens with the basal forebrain.  It can receive bottom-up information from the body – especially the visceral organs (Bentley et al, Bernston et al)

SLRs, and The hand that turns the aperture ring?

When taking a photograph on a manual camera, the person doing the pointing-and-shooting must adjust the aperture to determine how much of the entire scene comes into focus.  The aperture ring does not decide, on its own, what to ‘pay attention to’.  The same is true of the basal forebrain, the export region from which all of the acetylcholine that rains down on the cortex.  If Ach is the aperture ring, and the basal forebrain is the hand that turns it, then the person who owns the hand is the higher value-encoding regions of the brain.  Virtually all subcortical regions receive top-down attentional control telling them what sensory information they should filter out, and what they should let through (Pessoa et al).  The basal forebrain receives input from both so-called executive regions of the brain (Zaborsky et al) and, simultaneously though by more indirect roots, from limbic value-processing regions (Sarter et al 2000), which in conjunction essence ‘tell’ it where to focus attention. That is, as with taking a picture, both emotional and more purely rational parts of the brain collaborate to decide how much to put into focus – how much to turn the ring.

Attention, Reward, Learning and Memory

Literature and mythology is replete with characters who are unique and charming by virtue of their peculiar tendency to pay attention to aspects of a situation that most people would not.  For example, the historian who stumbles into an ancient tomb filled with gold, but while his companions fill their bags with loot, focuses instead on the inscription on the wall.  Or to take an opposite example, the simpleton who, upon being held up at gunpoint and only one wrong move away from death, innocently and calmly tells the criminal that he needs to wash his hands before supper, and asks to be excused – clueless about the threat he faces.  Inadvertently what these scenes show us is the robust link between attention and reward or punishment.  It is normal, at the psychological level, to pay attention to both threats and rewards, danger and safety, wealth, beauty, danger, anger, rivals, and any of a thousand examples of things in the environment that hold our safety, health, status, and relationships in the balance.

We should expect, therefore, that the machinery of the brain would contain mechanisms by which attention and reward are linked. There is some evidence (Wilson and Rolls) that memories of a stimulus as being rewarding allow the prefrontal cortex to command the basal forebrain to focus attention (release acetylcholine) on these stimuli when they are encountered in the environment.  For example, if you have had a good pizza dinner at a restaurant, and unexpectedly walk past it one Saturday night, your PFC may trigger the basal forebrain to focus attention on the restaurant.

Further Reading & References

denotes excellent papers

** denotes exceptionally useful papers

  • ** Sarter et al. Unraveling the attentional functions of cortical cholinergic inputs: interactions between signal-driven and cognitive modulation of signal detection. Brain Res Brain Res Rev (2005) vol. 48 (1) pp. 98-111
  • S. Penschuck, C.H. Chen-Bee, N. Prakash, R.D. Frostig, In vivo
    modulation of a cortical functional sensory representation shortly
    after topical cholinergic agent application, J. Comp. Neurol. 452
    (2002) 38 – 50.
  • E. Mercado, S. Bao, I. Orduna, M.A. Gluck, M.M. Merzenich, Basal
    forebrain stimulation changes cortical sensitivities to complex sound,
    NeuroReport 12 (2001) 2283 – 2287.
  • M.P. Kilgard, M.M. Merzenich, Cortical map reorganization enabled
    by nucleus basalis activity, Science 279 (1998) 1714 – 1718.
  • Kimura, M. Fukuda, T. Tsumoto, Acetylcholine suppresses the
    spread of excitation in the visual cortex revealed by optical
    recording: possible differential effect depending on the source of input. Eur. J. Neurosci. 11 (1999) 3597 – 3609.
  • M.E. Hasselmo, J. McGaughy, High acetylcholine levels set circuit
    dynamics for attention and encoding and low acetylcholine levels
    set dynamics for consolidation., Prog. Brain Res. 145 (2004)
    201 – 231.
  • N.M. Weinberger, The nucleus basalis and memory codes: auditory
    cortical plasticity and the induction of specific, associative behav-
    ioral memory, Neurobiol. Learn. Mem. 80 (2003) 268 – 284.
  • A.C. Roberts, T.W. Robbins, B.J. Everitt, G.H. Jones, T.E. Sirkia, J.
    Wilkinson, K. Page, The effects of excitotoxic lesions of the basal
    forebrain on the acquisition, retention and serial reversal of visual
    discriminations in marmosets, Neuroscience 34 (1990) 311 – 329.
  • L. Zaborszky, R.P. Gaykema, D.J. Swanson, W.E. Cullinan, Cortical
    input to the basal forebrain, Neuroscience 79 (1997) 1051 – 1078.
  • M. Sarter, J.P. Bruno, Cortical cholinergic inputs mediating arousal,
    attentional processing and dreaming: differential afferent regulation of the basal forebrain by telencephalic and brainstem afferents, Neuroscience 95 (2000) 933 – 952.
  • P. Bentley, P. Vuilleumier, C.M. Thiel, J. Driver, R.J. Dolan,
    Cholinergic enhancement modulates neural correlates of selective
    attention and emotional processing, Neuroimage 20 (2003) 58 – 70.
  • P. Bentley, P. Vuilleumier, C.M. Thiel, J. Driver, R.J. Dolan, Effects
    of attention and emotion on repetition priming and their modulation by cholinergic enhancement, J. Neurophysiol. 90 (2003) 1171 – 1181.
  • G.G. Berntson, M. Sarter, J.T. Cacioppo, Anxiety and cardiovascular
    reactivity: the basal forebrain cholinergic link, Behav. Brain Res. 94
    (1998) 225 – 248.
  • ** L. Pessoa, S. Kastner, L.G. Ungerleider, Neuroimaging studies of
    attention: from modulation of sensory processing to top-down
    control, J. Neurosci. 23 (2003) 3990 – 3998.
  • F.A. Wilson, E.T. Rolls, Learning and memory is reflected in the
    responses of reinforcement-related neurons in the primate basal
    forebrain, J. Neurosci. 10 (1990) 1254 – 1267.
  • * A.J. Yu, P. Dayan, Acetylcholine in cortical inference, Neural Netw.
    15 (2002) 719 – 730.

2 thoughts on “The Navy SEAL’s Acetylcholine

  1. “the most important single shot in American history since 1776”

    This is doubtful considering Bin Laden wasn’t responsible for the majority of offenses that he got pinned for. Aiming the scope towards the ex-president and all his cronies would have been the single most important shot in history to the end of time. Bin Laden was a scapegoat and his reputation was based on media lies.

  2. Information. Lucky me personally I ran across your website by chance, and I’m astonished precisely why this specific twist of fate did not came to exist upfront! We book-marked it.

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

About Peter Freed, M.D.

I am a psychiatrist (psychopharmacology and psychotherapy) specializing in the so-called "personality disorders," particularly narcissistic and borderline personality disorders. I was a Fellow and then an Assistant Professor of Clinical Psychiatry at Columbia from 2004- 2011. I am currently in private practice in NYC.