Hey everyone, new to this forum but I have lots of questions with the way this study was performed/interpreted. I'm glad others have noticed the disparity between the analysis of the fMRI data versus the MEP data, specifically by not standardizing the comparisons across fatigue onset. I've been approved for access to the data repository so I am going to attempt to re-analyze it to see if there is still a significant difference in TPJ BOLD signal when this is controlled for, as the most significant difference seems to be during two sets of blocks where the majority of HVs had not reached muscle fatigue while most of the PI-ME participants had.
I am also incredibly puzzled by the interpretation of the TPJ results. The paper that Walitt keeps citing for this is a recent hypothesis paper, and reading it has left me with far more questions than answers. I'm a neuroscientist but I mostly deal with the realms of pharmacology, cell biology, genetics, and animal behavior; cognitive neuroscience and neuroimaging have always been a bit too theoretical for my hyper-literal brain to fully grasp. So I'm gathering as much as I can but hoping to connect with someone who works in this area and can help explain the logic behind the interpretation of the data.
Compared to HVs, PI-ME/CFS participants failed to maintain a moderate grip force even though there was no difference in maximum grip strength or arm muscle mass. This difference in performance correlated with decreased activity of the right temporal-parietal junction, a part of the brain that is focused on determining mismatch between willed action and resultant movement(31). Mismatch relates to the degree of agency, i.e., the sense of control of the movement(32). Greater activation in the HVs suggests that they are attending in detail to their slight failures, while the PI-ME/ CFS participants are accomplishing what they are intending.
So first of all, the references: ref 31 is the hypothesis paper about the functionality of the TPJ, and ref 32 is a research study from 2011 that tested self-agency by having participants wear a specialized glove that can basically transmit the data on its position and display a hand figure on a screen that the participant watches while undergoing the fMRI. They would then reduce the accuracy of the figure so that the proprioceptive information (where your brain thinks your hand is in space) and the visual representation (the figure on the screen) are in conflict. The TPJ seems to be one of them, but there are bunch of others in this network (they mention PPC, STS, DLPFC, pre-SMA, precuneus, insula, and cerebellum).
Basically, from this we've learned that a mismatch between proprioception and visual feedback can activate the TPJ. The hypothesis paper discusses a lot of studies that found TPJ activation via fMRI in certain contexts like "theory of mind" studies (basically the ability to understand someone else's state of mind based on context), episodic memory tasks, and attention/orienting tasks like the Posner task. But then this quote stuck out to me, emphasis added:
Similarly, the right TPJ modulates the SoA, i.e. perceiving that one is the cause of her/his actions [47,48]. Findings from fMRI studies show that the AG and SMG in the right TPJ display increased activity when visual or proprioceptive signals mismatch the movement that is being performed [48–52]. In this case, one has the feeling that somebody else is responsible for her/his own movement, which causes the loss of the sense of agency [53]. Significantly, TMS inactivation of the right TPJ compromises the sense of agency, thus suggesting a functional causative role for this area [54,55]. Frith and co-workers (review in [50]) and Brass and co-workers (review in Quesque and Brass [56]) have both emphasised that the sense of agency is grounded in one’s ability to distinguish whether sensory-proprioceptive feedback signals are congruent or not with those expected from the performance of a willed action. When they are not, the action is perceived as unwilled or as originating from an external cause or agent, thus producing the self-other distinction.
I'm interpreting this to mean that rTPJ is activated when sensory feedback does not align with expected performance, which results in feeling a lack of agency. Importantly, this loss of agency has been induced either by manipulating visual feedback (i.e. using virtual reality) or by directly stimulating/deactivating the TPJ via TMS. I did a few PubMed/Google Scholar searches to see if any studies had looked at TPJ activation during repetitive motor tasks to try and determine whether reaching a point of muscle fatigue can also induce the perception of a loss of agency. To my mind at least, it seems like there could be a difference between a proprioceptive/visual mismatch and the failure to perform a motor task due to muscle fatigue. I didn't find anything - that doesn't mean it doesn't exist, but it does mean that the conclusions Walitt et al draw from this result are basically speculative, right? This wouldn't bother me if it was framed as such, but the paper discusses it as though it's widely implicated during muscle fatigue, which it does not appear to be in any way.
(I'll continue in another post, getting tired and this is getting long but I have many more thoughts I'd like to share)