– does sophisticated MRI data point us to optimal treatment?
This blog was first published on 25th January 2018 on BMJ Blogs, this blog has been removed, so it was reproduced here.
For some time, a group on the US east coast have been quietly scanning brains with functional magnetic resonance imaging (fMRI) and related techniques to examine the effects of acupuncture. They hit the headlines in rather a dramatic manner in 2017.[1,2]
At the beginning of the fMRI story, we saw some extraordinary claims concerning point specificity in acupuncture from a famous name in the development of fMRI, but these were later retracted. I was relieved to see the retraction, as the claims did not seem mechanistically credible from a neurophysiological point of view. The authors retracted their paper because the results were not in line with the body of developing evidence that acupuncture with typical deep tissue sensation (I prefer this term, but it equates to de qi) seems to cause a general deactivation of limbic structures,[4,5] rather than specific and targeted functional activations.
So why am I a year behind the headlines? Well, I was asked to discuss the research for a television programme, so I read the paper thoroughly in preparation and discovered an interesting observation that had previously escaped my notice. Then there was a mix-up with storyboards, and we discussed other research instead. So, I thought I had better put all those hours of preparation to good use by describing my thoughts on this rather complex area of research.
The team concerned here first came to my attention when they demonstrated a change in cortical mapping of the second and third fingers (D2/D3) in patients with carpal tunnel syndrome (CTS) treated with acupuncture. This was a departure from the fMRI studies prior, which had tended to simply watch what happened in the brain after acupuncture or control procedures in healthy subjects. Whilst it was an interesting finding, the study was observational rather than a strict RCT, and I felt that the change in cortical mapping was likely to be downstream of the main effects of acupuncture rather than a direct effect, ie a consequence of the acupuncture mechanism rather than part of the mechanism. This is always the problem with observational data – is the observed association causal or consequential?
The team continued to study CTS, and the research published in 2017 was a three-armed study of 80 patients with CTS  – a large study in fMRI terms, but small and underpowered in terms of standard clinical trials of acupuncture in pain. The 3 different interventions principally involved electroacupuncture (EA): local EA (PC7–TE5), distant contralateral EA (SP6–LR4) and ipsilateral regional sham EA (non-points on the flexor aspect of the mid forearm). Manual points were included in the same regions as the EA in each group.
The symptom scores in all groups declined over the course of treatment with no significant differences, although noticeably bigger change scores in the local and sham groups, where the focus of treatment was in the correct limb. Despite this, the median nerve conduction latency improved in both EA groups and deteriorated in the sham EA group. D2/D3 cortical separation distance improved marginally more (not significant) with local EA than distant EA, and not at all in the sham.
…median nerve conduction latency and D2/D3 cortical separation distance improved in both EA groups
So despite there being no difference between groups in terms of symptoms, there was a clear difference in objective measures of nerve function and brain function. And there is more! The degree of improvement in D2/D3 cortical separation distance immediately after the 8-week 16-session treatment course predicted (correlated with) the symptom score at 3 months follow-up. That is very interesting, and somewhat counters my assumption that the cortical remapping is downstream (ie a consequence rather than a cause) of the effect of EA.
The degree of improvement in D2/D3 cortical separation distance correlated with the symptom score at 3 months follow-up
Another interesting aspect is the rate of deterioration in symptom score of the sham group after they were unmasked, and the continued improvement of the distal group after they learned that they had a genuine treatment. This makes me ponder over the influence of other brain centres – those related to cognition analysis and expectation – and how these can add unwanted noise in group means for subjective outcomes.
And there is still more! The bit I originally missed because it was just too much effort to read and understand. The team studied the microstructure of the white matter adjacent to the relevant areas of the primary somatosensory cortex (S1). I didn’t even know this was possible, but it has been around for about 15 years. Fractional anisotropy is a measure of order in the structure of white matter based on diffusion of water. A perfect isotropic material would have an even pattern of diffusion in all directions, but uniform tracts of myelinated neurones will disturb this, and cause a degree of anisotropy. Got it? Anyway, the team discovered that the changes after real EA (local & distant) in fractional anisotropy near the S1 cortex related to the contralesional hand correlated with latency changes in the median nerve. This was not true of sham. Even more interesting is that this correlation between changes in fractional anisotropy and median nerve latency occurred in different areas of the ipsilesional SI cortex depending on whether the EA was local or distant.
This has to be considered speculative, since it was a bit of a fishing trip, but it is very exciting to speculate that in the future we may be able to develop ways of tracking the course of plastic changes in the central nervous system and design optimal treatment approaches as a result; moving us from ancient philosophy, through neuroscience from the last century (segmental neuromodulation) perhaps to real-time neural remodelling.
1 Ditch the paracetamol and try ACUPUNCTURE. Daily Mail Online 2017. http://www.dailymail.co.uk/health/article-4274898/Ditch-paracetamol-try-ACUPUNCTURE.html (accessed 24 Jan2018).
2 Maeda Y, Kim H, Kettner N, et al. Rewiring the primary somatosensory cortex in carpal tunnel syndrome with acupuncture. Brain 2017;140:914–27. doi:10.1093/brain/awx015
3 Cho ZH, Chung SC, Lee HJ, et al. Retraction. New findings of the correlation between acupoints and corresponding brain cortices using functional MRI. Proc Natl Acad Sci U S A 2006;103:10527. doi:10.1073/pnas.0602520103
4 Wu MT, Hsieh JC, Xiong J, et al. Central nervous pathway for acupuncture stimulation: localization of processing with functional MR imaging of the brain–preliminary experience. Radiology 1999;212:133–41.http://www.ncbi.nlm.nih.gov/pubmed/10405732 (accessed 28 Aug2011).
5 Hui KK, Liu J, Makris N, et al. Acupuncture modulates the limbic system and subcortical gray structures of the human brain: evidence from fMRI studies in normal subjects. Hum Brain Mapp 2000;9:13–25.
6 Napadow V, Liu J, Li M, et al. Somatosensory cortical plasticity in carpal tunnel syndrome treated by acupuncture. Hum Brain Mapp 2007;28:159–71. doi:10.1002/hbm.20261