In recent weeks there have been a couple of articles that
have revisited the question of the importance (or not) of the results of fMRI
studies (http://www.theguardian.com/science/head-quarters/2014/mar/26/brain-imaging-scan-fmri-academic-gimmick
and http://www.theguardian.com/science/head-quarters/2014/mar/13/brain-scans-imaging-behaviour-mind).
For me the importance of fMRI to address any research question is dependent on
the degree to which the hypothesis requires specific predictions about the
underlying neuronal signals. In general, the more any hypothesis is dependent
upon specific neuronal parameters the less convincing the results and
conclusions of that study will be. Currently, we still do not know with any confidence
how the BOLD signal in humans is modulated by neuronal firing rate and/or by
modulations in the amplitude of the local field potentials at different
frequencies. In addition, we have virtually no data that addresses how any
relationships between the neuronal measures and the BOLD signal might differ in
different brain regions. Indeed Harris et al. (2011) wrote “In particular, BOLD
signals need not directly report spiking activity in the imaged area, but
instead reflect the many factors associated with neural activity that lead to an
increase in blood flow. Most importantly, neurotransmitters released during
synaptic activation are now known to directly influence local blood flow and it
is thought that the BOLD signal may most closely reflect the excitatory synaptic
component, rather than the action potential component, of neural activity”. Therefore,
it would seem that it would be prudent to reduce the weight given to fMRI
results that purport to reflect changes to specific parameters of the
underlying neuronal signal. A good case study that demonstrates the difficulty
in relating neuronal signal modulations to BOLD signal modulations is the
history of using fMRI to investigate the presence (or not) of mirror neurons in
humans. Which is still unresolved.
However, not all fMRI experiments have hypotheses that are
based on specific predictions about the underlying neuronal signals. Indeed, it
is interesting to note that the examples given in support of fMRI research by
Matt Wall (http://www.theguardian.com/science/head-quarters/2014/mar/26/brain-imaging-scan-fmri-academic-gimmick)
are examples of such research. Here, the fMRI signal is employed as a
biomarker, without any attempt to explain or link any modulations in the BOLD
signal to specific neuronal parameters. So, does it matter that we do not know
the link between neuronal signals and the BOLD response? I would say – it depends.
It depends on whether your hypothesis makes specific predictions about the underlying
neuronal signal or not. If it does then it clearly does matter that the link
between neuronal signals and the BOLD response is not known. If not, then it
does not matter.
What ever your thoughts this paper is well worth a read.
Harris JJ, Reynell C, Attwell D. (2011) The physiology of
developmental changes in BOLD functional imaging signals. Dev Cogn Neurosci. 1(3):199-216.
http://goo.gl/wGYqlX
James,
ReplyDeleteMany thanks for the comment - really valuable. My thought is that ideally fMRI researchers should keep all the issues you highlight at the front of their minds when making interpretations of their data. That's easier said than done though - sometimes it's easy to get carried away by a nice result!
It's a tricky issue - of course you're absolutely right that we desperately need to develop a better understanding of exactly what the BOLD response is and how it relates to neural activity - the issue that it's never been documented how BOLD differs in different brain regions is just one of many gaps in our knowledge. At the same time, a lot of work has shown that there *is* a relationship of some kind between BOLD and neural activity. Researchers need regular reminders that the issue is not as settled as we'd like it to be.
For me, some of the most interesting and thoughtful fMRI research are those papers that seek to dig a little deeper and try to infer something about the underlying neural response. fMRI-adaptation studies are a good example of this (nice review here: http://faculty.washington.edu/gboynton/publications/krekelberg-TINS06.pdf). I've often wondered why more people don't use adaptation designs; though of course they have their own set of associated problems.
Which brings me back to the conclusion of that Conversation/Guardian article - no one research methodology is enough. In order to make progress with tackling the issues you mention, we'll need to use all the tools in our toolbox, and fMRI is just one of them.
Thanks again for the comment - and I'll be reading that Harris et al. paper tomorrow!