Causation in neuroscience: keeping mechanism meaningful.

A fundamental goal of research in neuroscience is to uncover the causal structure of the brain. This focus on causation makes sense, because causal information can provide explanations of brain function and identify reliable targets with which to understand cognitive function and prevent or change neurological conditions and psychiatric disorders. In this research, one of the most frequently used causal concepts is 'mechanism' - this is seen in the literature and language of the field, in grant and funding inquiries that specify what research is supported, and in journal guidelines on which contributions are considered for publication. In these contexts, mechanisms are commonly tied to expressions of the main aims of the field and cited as the 'fundamental', 'foundational' and/or 'basic' unit for understanding the brain. Despite its common usage and perceived importance, mechanism is used in different ways that are rarely distinguished. Given that this concept is defined in different ways throughout the field - and that there is often no clarification of which definition is intended - there remains a marked ambiguity about the fundamental goals, orientation and principles of the field. Here we provide an overview of causation and mechanism from the perspectives of neuroscience and philosophy of science, in order to address these challenges.

Polygene risk scores and randomized experiments.

We explore Madole & Harden's (2022) suggestion that single-nucleotide polymorphism (SNP)/trait correlations are analogous to randomized experiments and thus can be given a causal interpretation.

A call for more clarity around causality in neuroscience.

In neuroscience, the term 'causality' is used to refer to different concepts, leading to confusion. Here we illustrate some of those variations, and we suggest names for them. We then introduce four ways to enhance clarity around causality in neuroscience.

Koch's postulates: An interventionist perspective.

We argue that Koch's postulates are best understood within an interventionist account of causation, in the sense described in Woodward (2003). We show how this treatment helps to resolve interpretive puzzles associated with Koch's work and how it clarifies the different roles the postulates play in providing useful, yet not universal criteria for disease causation. Our paper is an effort at rational reconstruction; we attempt to show how Koch's postulates and reasoning make sense and are normatively justified within an interventionist framework and more difficult to understand within alternative frameworks for thinking about causation.

Kinetics and regioselectivity of ring opening of 1-bicyclo[3.1.0]hexanylmethyl radical.

Rate constants for the rearrangement of 1-bicyclo[3.1.0]hexanylmethyl radical (2) to 3-methylenecyclohexenyl radical (3) and 2-methylenecyclopentyl-1-methyl radical (1) were measured using the PTOC-thiol competition method. The ring-expansion pathway is described by the rate equation, log(k/s-1) = (12.5 +/- 0.1) - (4.9 +/- 0.1)/theta; the non-expansion pathway is described by log(k/s-1) = (11.9 +/- 0.6) - (6.9 +/- 0.8)/theta. Employing the slower trapping agent, tri-n-butylstannane, favors methylenecyclohexane over 2-methyl-methylenecyclopentane by more than 120:1 at ambient or lower temperatures.