Determined, page 21
Why has this organization evolved, instead of the single-bucket approach? Probably because it gives you more fine control. For example, it turns out that a large percentage of vesicles are usually mothballed at the back end of the terminal, kept in storage for when needed. Therefore, an action potential doesn’t really cause the release of neurotransmitter from all the vesicles in each axon terminal. More correctly, it causes releases from all of the vesicles in the “readily releasable pool.” And neurons can regulate what percentage of their vesicles are readily releasable versus in storage, a way of changing the strength of the signal across the synapse.
This was the work of Bernard Katz, who got some of his training with Eccles and went on to his own knighthood and Nobel Prize. Katz would isolate a single neuron and, with the use of a particular drug, make it impossible for it to have an action potential. He’d then study what would be happening at a given axon terminal. What he saw was that, amid action potentials being blocked, every now and then, maybe once a minute,[*] the axon terminal would release a tiny hiccup of excitation, something eventually called a miniature end-plate potential (MEPP). Showing that little bits of neurotransmitter were spontaneously and randomly released.
Katz noted something interesting. The hiccups were all roughly the same size, say, 1.3 smidgens of excitation. Never 1.2 or 1.4. To the limits of measurement, always 1.3. And then, after sitting there recording the occasional 1.3 smidgen-size blip, Katz noticed that much more rarely than that, there’d be a hiccup that was 2.6 smidgens. Whoa. And even more rarely, 3.9 smidgens. What was Katz seeing? 1.3 smidgens was the amount of excitation of one single vesicle being spontaneously released; 2.6, the much rarer spontaneous release of two vesicles simultaneously, and so on.[*] From that came the insight that neurotransmitters were stored in individual vesicular packets, and that every now and then, in a purely probabilistic fashion, an individual vesicle would dump its neurotransmitters—drumroll please—in the absence of an antecedent cause.[*],[13]
While the field has often viewed the phenomenon as not hugely interesting, often referring to it semisarcastically as “leaky synapses,” the notion of there being no antecedent causes turned spontaneous vesicular release of neurotransmitter into an amusement park in which neuroquantologists can gambol. Aha, spontaneous, nondeterministic vesicular neurotransmitter release as the building block for the brain as a cloud of potentials, for being the captain of your fate. Four reasons to be very cautious about this:[14]
—Not so fast with the no-antecedent-cause part. There’s a whole cascade of molecules involved in the process of an action potential causing vesicles to dump their neurotransmitter into the synapse—ion channels open or close, ion-sensitive enzymes are activated, a matrix of proteins holding a vesicle still in its inactive state has to be cleaved, a molecular machete has to cut through more matrix to allow the vesicle to then move toward the neuron’s membrane, the vesicle has to now dock to a specific release portal in the membrane. The insights of many fruitful careers in science. Okay, you think you see where I’m going—yeah, yeah, neurotransmitter doesn’t just get dumped from out of nowhere, there’s this whole complex mechanistic cascade explaining intentional neurotransmitter release, so we’ll reframe our free will as when this deterministic cascade happens to be triggered in the absence of an antecedent cause. But no—it’s not just when the usual process is triggered randomly, because it turns out that the mechanistic cascade for spontaneous vesicular release is different from the cascade for release evoked by an action potential. It’s not a random universe hitting a button that normally represents intent. A separate button evolved.[15]
—Moreover, the process of spontaneous vesicular release is regulated by factors extrinsic to the axon terminal—other neurotransmitters, hormones, alcohol, having a disease like diabetes, or having a particular visual experience can all alter spontaneous release without having a similar effect on evoked neurotransmitter release. Events in your big toe can change the likelihood of these hiccups happening in the axon terminal of some neuron in the corner of your brain. How would, say, a hormone do this? It sure wouldn’t be changing the fundamental nature of quantum mechanics (“Ever since puberty and hormones hit, all I get from her is sullenness and quantum entanglement”). But a hormone can alter the opportunity for quantum events to occur. For example, many hormones change the composition of ion channels, changing how subject they are to quantum effects.[16]
Thus, deterministic neurobiology can make indeterministic randomness more or less likely to occur. It’s like you’re the director of a show where, at some point, the new king emerges, to much acclaim. And as your direction, you tell the twenty people in the ensemble, “Okay, when the king appears from stage left, shout out stuff like ‘Hoorah!’ ‘Behold, the king!’ ‘Long life, sire!’ ‘Huzzah!’—just pick one of those.”[*] And you’re pretty much guaranteed to get the mélange of responses you were aiming for. Determined indeterminacy. This certainly does not count as randomness being an uncaused cause.[17]
—Spontaneous vesicular release of neurotransmitters serves a useful purpose. If a synapse has been silent for a while, the likelihood of spontaneous release increases—the synapse gets up and stretches a bit. It’s like, during a long period at home, running the car occasionally to keep the battery from dying.[*] In addition, spontaneous neurotransmitter release plays a large role in the developing brain—it’s a good idea to excite a newly wired synapse a bit, make sure everything is working right, before putting it in charge of, say, breathing.[18]
—Finally, there’s still the bubbling-up problem.
The bubbling issue brings us to our next level. So individual vesicles randomly dump their contents now and then, ignoring for the moment the issues of its involving unique machinery, being intentionally regulated, and being purposeful. Do enough vesicles ever get dumped all at once to make a major burst of excitation in a single synapse? Unlikely; an action potential evokes about forty times the excitation as does the spontaneous dump of a single vesicle.[*] You’d need a lot of those hiccups at once to produce this.
Scaling up one step higher, do neurons ever just randomly have action potentials, dumping vesicles in all ten thousand to fifty thousand axon terminals, seemingly in the absence of an antecedent cause?
Now and then. Have we now leapfrogged up to a more integrated level of brain function that could be subject to quantum effects? The same caution is called for again. Such action potentials have their own mechanistic antecedent causes, are regulated extrinsically, and serve a purpose. As an example of the last point, neurons that send their axon terminals into muscles, stimulating muscle movement, will have spontaneous action potentials. It turns out that when the muscle has been quiet for a while, a part of it (called the muscle spindle) can make the neurons more likely to have spontaneous action potentials—when you’ve been still for a long while, your muscles get twitchy, just so the battery doesn’t run down.[*] Another case where a mechanistic, deterministic regulatory loop can make indeterministic events more likely. Again, we’ll get to what to make of such determined indeterminacy.
One level higher—do entire networks, circuits of neurons, ever activate randomly? People used to think so. Suppose you’re interested in what areas of the brain respond to a particular stimulus. Stick someone in a brain scanner and expose them to that stimulus, and see what brain regions activate (for example, the amygdala tends to activate in response to seeing pictures of scary faces, implicating that brain region in fear and anxiety). And in analyzing the data, you would always have to subtract out the background level of noisy activity in each brain region, in order to identify what was explicitly activated by the stimulus. Background noise. Interesting term. In other words, when you’re just lying there, doing nothing, there’s all sorts of random burbling going on throughout the brain, once again begging for an indeterminacy interpretation.
Until some mavericks, principally Marcus Raichle of Washington University School of Medicine, decided to study the boring background noise. Which, of course, turns out to be anything but that—there’s no such thing as the brain doing “nothing”—and is now known as the “default mode network.” And, no surprise by now, it has its own underlying mechanisms, is subject to all sorts of regulation, serves a purpose. One such purpose is really interesting because of its counterintuitive punch line. Ask subjects in a brain scanner what they were thinking at a particular moment, and the default network is very active when they are daydreaming, aka “mind-wandering.” The network is most heavily regulated by the dlPFC. The obvious prediction now would be that the uptight dlPFC inhibits the default network, gets you back to work when you’re spacing out thinking about your next vacation. Instead, if you stimulate someone’s dlPFC, you increase activity of the default network. An idle mind isn’t the Devil’s playground. It’s a state that the most superego-ish part of your brain asks for now and then. Why? Speculation is that it’s to take advantage of the creative problem solving that we do when mind-wandering.[19]
* * *
• • •
What is to be made of these instances of neurons acting spontaneously? Back, once again, to the show-me scenario—if free will exists, show me a neuron(s) that just caused a behavior to occur in the complete absence of any influences coming from other neurons, from the neuron’s energy state, from hormones, from any environmental events stretching back through fetal life, from genes. On and on. And none of the versions of ostensibly spontaneous activation of a single vesicle, synapse, neuron, or neuronal network constitutes an example of this. None are truly random events that could be directly rooted in quantum effects; instead, they are all circumstances where something very mechanistic in the brain has determined that it’s time to be indeterministic. Whatever quantum effects there are in the nervous system, none bubble up to the level of telling us anything about someone pulling a trigger heartlessly or heroically.
Problem #2: Is Your Free Will a Smear?
Which brings us to the second big problem with the idea that quantum mechanics means that our macroscopic world cannot actually be deterministic and free will is alive and well. Rather than the technicalities of leaky synapses, muscle spindles, and quantumly entangled vesicles, this problem is simple. And, in my opinion, devastating.
Suppose there were no issues with bubbling—indeterminacy at the quantum level was not canceled out in the noise and instead shaped macroscopic events dozens of orders of magnitude larger in size. Suppose the functioning of every part of your brain as well as your behavior could most effectively be understood on the quantum level.
It’s difficult to imagine what that would look like. Would we each be a cloud of superimposition, believing in fifty mutually contradictory moral systems at the same time? Would we simultaneously pull the trigger and not pull the trigger during the liquor store stickup, and only when the police arrive would the macro-wave function collapse and the clerk be either dead or not?
This raises a fundamental problem that screams out, one that every stripe of scholar thinking about this topic typically wrestles with. If our behavior were rooted in quantum indeterminacy, it would be random. In his influential 2001 essay “Free Will as a Problem in Neurobiology,” philosopher John Searle wrote, “Quantum indeterminism gives us no help with the free will problem because that indeterminism introduces randomness into the basic structure of the universe, and the hypothesis that some of our acts occur freely is not at all the same as the hypothesis that some of our acts occur at random. . . . How do we get from randomness to rationality?”[*] Or as often pointed out by Sam Harris, if quantum mechanics actually played a role in supposed free will, “every thought and action would seem to merit the statement ‘I don’t know what came over me.’ ” Except, I’d add, you wouldn’t actually be able to make that statement, since you’d just be making gargly sounds because the muscles in your tongue would be doing all sorts of random things. As emphasized by Michael Shadlen and Adina Roskies, whether you believe that free will is compatible with determinism, it isn’t compatible with indeterminism.[*] Or in the really elegant words of one philosopher, “Chance is as relentless as necessity.”[20]
When we argue about whether our behavior is the product of our agency, we’re not interested in random behavior, why there might have been that one time in Stockholm where Mother Teresa pulled a knife on some guy and stole his wallet. We’re interested in the consistency of behavior that constitutes our moral character. And in the consistent ways in which we try to reconcile our multifaceted inconsistencies.[*] We’re trying to understand how Martin Luther would stick to his guns and say, “Here I stand, I can do no other,” when ordered to renounce his views by ecumenical thugs who burned people at the stake as a hobby. We’re trying to understand that lost-cause person who is trying to straighten out their life yet makes self-destructive, impulsive decisions again and again. It’s why funerals so often include a eulogy from that person’s oldest friend, a historical witness to consistency: “Even when we were in grade school, she already was the sort of person who . . .”
Even if quantum effects bubbled up enough to make our macro world as indeterministic as our micro one is, this would not be a mechanism for free will worth wanting. That is, unless you figure out a way where we can supposedly harness the randomness of quantum indeterminacy to direct the consistencies of who we are.
Problem #3: Harnessing the Randomness of Quantum Indeterminacy to Direct the Consistencies of Who We Are
Which is precisely what is argued by some free-will believers leaning on quantum indeterminacy. In the words of Daniel Dennett in describing this view, “Whatever you are, you can’t influence the undetermined event—the whole point of quantum indeterminacy is that such quantum events are not influenced by anything—so you will somehow have to co-opt it or join forces with it, putting it to use in some intimate way” (my italics). Or in the words of Peter Tse, your brain “would have to be able to harness this randomness to fulfill information processing aims.”[21]
I see two broad ways of thinking about how we might harness, co-opt, and join forces with randomness for moral consistency. In a “filtering” model, randomness is generated indeterministically, the usual, but the agentic “you” installs a filter up top that allows only some of the randomness that has bubbled up to pass through and drive behavior. In contrast, in a “messing with” model, your agentic self reaches all the way down and messes with the quantum indeterminacy itself in a way that produces the behavior supposedly chosen.
Filtering
Biology provides at least two fantastic examples of this sort of filtering. The first is evolution—the random physical chemistry of mutations occurring in DNA provides genotypic variety, and natural selection is then the filter choosing which mutations get through and become more common in a gene pool. The other example concerns the immune system. Suppose you get infected with a virus that your body has never seen before; thus, there’s no antibody against it in your body’s medicine cabinet. The immune system now shuffles some genes to randomly generate an enormous array of different antibodies. At which point filtering begins. Each new type of antibody is presented with a piece of the virus, to see how well the former reacts to the latter. It’s a Hail Mary pass, hoping that some of these randomly generated antibodies happen to target the virus. Identify them, and then destroy the rest of the antibodies, a process termed positive selection. Now check each remaining antibody type and make sure it doesn’t happen to do something dangerous as well, namely targeting a piece of you that happens to be similar to the viral fragment that was presented. Check each candidate antibody against a “self” fragment; find any that attack it and get rid of them and the cells that made them—negative selection. You now have a handful of antibodies that target the novel virus without inadvertently targeting you.[22]
As such, this is a three-step process. One—the immune system determines it’s time to induce some indeterministic randomness. Two—the random gene shuffling occurs. Three—your immune system determines which random outcomes fit the bill, filtering out the rest. Deterministically inducing a randomization process; being random; using predetermined criteria for filtering out the unuseful randomness. In the jargon of that field, this is “harnessing the stochasticity of hypermutation.”
Which is what supposedly goes on in the filtering version of quantum effects generating free will. In Dennett’s words:
The model of decision making I am proposing has the following feature: when we are faced with an important decision, a consideration-generator whose output is to some degree undetermined, produces a series of considerations, some of which may of course be immediately rejected as irrelevant by the agent (consciously or unconsciously). Those considerations that are selected by the agent as having a more than negligible bearing on the decision then figure in a reasoning process, and if the agent is in the main reasonable, those considerations ultimately serve as predictors and explicators of the agent’s final decision.[23]
As such, determining that you are at a decision-making juncture activates an indeterministic generator, and you then reason through which consideration is chosen.[*] As noted, Roskies does not equate the random noise of nervous systems (rooted in quantum indeterminacy or otherwise) with the headwaters of free will; instead, for Roskies, writing with Michael Shadlen, free will is what’s happening when you filter out the chaff from the wheat: “Noise puts a limit on an agent’s capacities and control, but invites the agent to compensate for these limitations by high-level decisions or policies[*] that may be (a) consciously accessible; (b) voluntarily malleable; and (c) indicative of character.” Filtering, picking, choosing as an act of sufficient free will and character that, as they state, this “can provide a basis for accountability and responsibility.”[24]
