Reach for the smelling salts: New paper 2018 to prove that abnormal beliefs cause ME disability (!)

[Snow Leopard]

This study can be interpreted quite differently, namely patients effectively predict their altered ability to effectively adjust performance at high exertion levels due to experienced fatigue (70% of their right hand maximal voluntary contraction - there were no differences at 50% and 30%)

CFS patients (as compared to HC) showed smaller increases in force after a “Too little” feedback, and larger decreases after a “Too much” feedback during 70% trials (T112=-2.65, p=0.009), but not during 50% trials (T112=1.85, p=.067) or 30% trials (T112=1.67, p=0.098; see Figure3A, FigureS3, Table2).

Pearson’s correlation analysis within the CFS group revealed that, on 70% trials, larger negative biases (i.e. smaller force increases after “Too little” feedback than correspondingly decreases after “Too much” feedback) were associated with higher levels of state-fatigue (CFS: r=-0.26, p=0.015, BF10=2.51; HC:r=.038, p=.85, BF10=0.24; no group interaction: T=-.83, p=.41) and lower performance expectations (CFS:r=0.37, p<.001, BF10=45.27; HC:r=.28, p=.14, BF10=0.65; no group interaction: T=.41,p=.68) (Figure3B/C). There were no significant correlations between the clinical trait variables (CIS-fatigue, SIPtotal, SF-36 and disease duration) and behavioural adjustment bias within the CFS group (all p>.05).

In terms of neuroimaging of brain activtity, there was no difference during the initial motor execution - there were only groupwise differences during feedback in the 70% max trials.

The differences in reduced vACC activity in CFS patient relative to controls on 70% trials might be meaningless given the weak effect, non association with any of the other variables and the P value of 0.04 is not significant when corrected for multiple corellations.

During feedback evaluation (70% trials), CFS patients showed reduced connectivity between SMA and the independently defined vACC-VOI compared to HC (xyz=-2,43,43, pfwe_VOI=0.006). This effect was specific for 70%,...

This seems interesting however seems to be due to non-specific lower SMA connectivity given:

During movement preparation, CFS patients showed reduced connectivity between SMA and sensorimotor cortex compared to HC (xyz = -32,-34,46, pfwe_VOI=0.013). Higher levels of state fatigue were associated with stronger connectivity in both groups (CFS: r=.25, p=.020, BF10=1.94; HC: r=.41, p=.029, BF10=2.23), and this relationship was stronger for HC than for CFS patients (T112=-2.55, p=.012)(Figure5D-F). Exploration over the whole brain did not reveal significant group differences in functional connectivity during feedback or preparation.

Sub-maximal physical performance and central activation failures have been suggested to result from disturbances in pre-motor brain regions leading to an inability of centrally derived motor commands to produce the intended force outputs (19, 37). Based on recent literature, we argue that these effects result from the first neurocomputational alteration, involving the comparison of predicted/intended sensory consequences and actual sensory evidence. In addition, we propose that this comparison likely involves the SMA and its connectivity with sensorimotor regions during motor preparation. Supporting this, the supplementary motor area (SMA) has been associated with the generation of predicted sensory consequences of actions(22, 38, 39), and with the willingness to engage in effortful behaviour(40, 41).

This is likely true, however the authors believe it is the SMA area that is dysfunctional, leading to incorrect effort perception, rather than the altered SMA activity or connectivity being associated with the experience of long term fatigue (and inconsistent performance at high levels of exertion). They cite literature that showed that disruption of the SMA lead to reduced effort perception - but what does this mean in terms of network connectivity and signalling?

http://www.jneurosci.org/content/35/23/8737.short


An interesting followup however was:
https://www.sciencedirect.com/science/article/pii/S1053811917307528
"cTBS disruption of the supplementary motor area perturbs cortical sequence representation but not behavioural performance"

Our findings question the causal link between the neuroimaging correlate of elementary motor sequence representation in the SMA and sequence generation, calling for a more thorough investigation of the role of this region in performance of learned motor sequences.

A discussion/hypothetical model of disruption and effort perception is here (well worth reading!):
http://www.jneurosci.org/content/35/39/13269.short

A substantial challenge facing empirical investigations of effort perception is the necessity of approaching an inherently private phenomenological experience with scientific rigor. In the 19thcentury, Bell (1826) and Sherrington (1900) proposed that the sensation of muscular forces originates from peripheral receptors, while Helmholtz (1867) posited that the perception of effort arises from internal signals generated by the central motor command. Although the question of how effort is perceived remains controversial, a current view, echoing that of Helmholtz, is that it arises primarily from efferent activity within the motor system. According to this model, when the brain initiates a motor command, it issues a parallel neural representation to predict the sensory consequences of that action (the corollary discharge or efference copy), which can then be used as an indicator of how subjectively effortful that action is (Carson et al., 2002). The centrality of the efference copy in effort perception is consistent with data showing that deafferented patients or those with suppressed sensory afferents can nevertheless perceive actions as effortful (Marcora, 2009).

Interestingly, although SMA stimulation showed significant effects relative to precuneus stimulation, there seemed to be no effect of either SMA or M1 stimulation in isolation on several objective measures (namely, effort replication intensity, pupil size, and perhaps force prediction, although direct statistical comparisons were not made between prestimulation and poststimulation blocks)