Abstract
This paper examines tracer techniques in neuroscience, which are used to identify neural connections in the brain and nervous system. These connections capture a type of “structural connectivity” that is expected to inform our understanding of the functional nature of these tissues (Sporns in Scholarpedia, 2007). This is due to the fact that neural connectivity constrains the flow of signal propagation, which is a type of causal process in neurons. This work explores how tracers are used to identify causal information, what standards they are expected to meet, the forms of causal information they provide, and how an analysis of these techniques contributes to the philosophical literature, in particular, the literature on mark transmission and mechanistic accounts of causation.
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Notes
As Sporns states “Neural activity, and by extension neural codes, are constrained by connectivity. Brain connectivity is thus crucial to elucidating how neurons and neural networks process information” (Sporns 2007).
This is especially the case when compared to identifying blood vessels and other more distinct anatomical structures.
Additional studies would need to be performed (likely in living specimens), to determine the direction of signal flow.
The self-replicating feature of viral tracers may seem to conflict with material continuity. While the particular material associated with the original, introduced viruses is unlikely to reliably flow across numerous neural connections, what matters is that it does flow across the synaptic junction (from one neuron to another). Material continuity is preserved at each causal link. A related point is discussed further in footnote 10.
This would occur, for example, if a radioactive molecule was attached to a phosphate group, which is spliced off a metabolite as it makes it way down a biochemical pathway. This is similar to attaching a bug to the coat of a spy, in order to trace them, while realizing at some later point in time, that they have removed their coat. Although the bug is still attached to the original material, this no longer follows the causal process of interest.
For example, if the spy keeps their coat on but the bug falls off, tracing efforts will again fail.
One exception to this third criterion is when the tracer reliably flows with material moving along a causal process, without directly tagging it. Examples of this are viral tracers in neural pathways and radioactive tracers in blood vessels and the gastrointestinal tract. Although some of these tracers do not directly tag material moving along the causal pathway, we have good reason to believe that they flow along with it.
Notice that signal transmission in neurons also involves receptors, in a way that is similar to this hormone example. Pre-synaptic neurons release neurotransmitters, these bind to receptors on postsynaptic neurons, and this binding triggers downstream effects. As material is not reliably moving from the neurotransmitter, to the receptor, to the downstream effects, this causal process appears to lack material continuity. If signal transmission in neurons lacks material continuity, is this a problem for my analysis, which claims that many neuroscientific tracers work by exploiting material continuity? No. The physical tracers discussed in this paper (viruses, dyes, radioactive markers, etc.) are not directly tracing signal transmission in neurons. They are tracing axonal transport and transynaptic processes that reliably move material (lysosomes and viruses, for example) along and across neurons. Tracing (a) axonal transport and (b) transsynaptic processes provides information about (c) signal transmission as all of these processes are constrained by the physical contours of neurons and their sequences of connections. Furthermore, (a) and (b) are far easier to tag and trace than (c), which helps explain why they are targeted with this methods. This is discussed in more detail shortly.
For example, signal tracers for electronic products and genetic tracers (that tag information) may count as cases of this.
For related discussion see Kästner’s distinction between interventions and mere interactions (Kästner 2017, p. 156).
Note that there are at least two different types of pathways in these cases. There are pathways that involve changes in the physical location of some material over time (neural and vascular pathways) and pathways that involve changes in the constitution of some material over time (metabolic and developmental pathways).
Scientists do use tracers to show that, for example, one neuron (1) is causally connected to another (2) on the basis of the fact that a tracer moves from (1) to (2). However, using tracers to establish this causal connection depends on the prior view of axonal transport processes as causal.
As Salmon and Reichenbach viewed their mark transmission accounts as supported by scientific tracer examples, the failure of this example to reflect scientific reasoning about tracers should raise a red flag.
Many of these views rely on a basic interventionist framework (Woodward 2003), but add much more in capturing the notion of “mechanism.”
While many diverse accounts of mechanistic explanation exist, some deny that mechanistic information involves fine-grained or significant causal detail (Bechtel and Levy 2013; Boone and Piccinini 2016; Craver and Kaplan 2020). My analysis relies on a “fine-grained detail” account of mechanism, which is suggested and argued for in other work (Machamer et al. 2000; Craver 2007; Darden 2006, Ross Forthcoming).
For more on these features and other examples of the pathway concept in science, see (Ross Forthcoming) and Ross (2018).
Pathways are also abstract in the sense that they represent complex processes with an economy of causal steps (Ross Forthcoming, p. 13). For example, the process of signal transmission from the spinal cord to the leg can be represented in anywhere from one to three causal connections, which abstract from an innumerable set of molecular steps.
If a tracer fails to move from one neural area to another, this suggests that these areas lack anatomical connection and functional involvement.
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Acknowledgements
I would like to thank James Woodward, Chris Hitchcock, David Danks, John Bickle, Carl Craver, and audience members at the “NeuroTech” conference, sponsored by the Mellon Institute and Center for Philosophy of Science at the University of Pittsburgh, for helpful comments on this paper.
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Ross, L.N. Tracers in neuroscience: Causation, constraints, and connectivity. Synthese 199, 4077–4095 (2021). https://doi.org/10.1007/s11229-020-02970-z
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DOI: https://doi.org/10.1007/s11229-020-02970-z