Reduced limbic microstructural integrity in functional neurological disorder, 2019, Diez et al

[Andy]

Background
Functional neurological disorder (FND) is a condition at the intersection of neurology and psychiatry. Individuals with FND exhibit corticolimbic abnormalities, yet little is known about the role of white matter tracts in the pathophysiology of FND. This study characterized between-group differences in microstructural integrity, and correlated fiber bundle integrity with symptom severity, physical disability, and illness duration.

Methods
A diffusion tensor imaging (DTI) study was performed in 32 patients with mixed FND compared to 36 healthy controls. Diffusion-weighted magnetic resonance images were collected along with patient-reported symptom severity, physical disability (Short Form Health Survey-36), and illness duration data. Weighted-degree and link-level graph theory and probabilistic tractography analyses characterized fractional anisotropy (FA) values across cortico-subcortical connections. Results were corrected for multiple comparisons.

Results
Compared to controls, FND patients showed reduced FA in the stria terminalis/fornix, medial forebrain bundle, extreme capsule, uncinate fasciculus, cingulum bundle, corpus callosum, and striatal-postcentral gyrus projections. Except for the stria terminalis/fornix, these differences remained significant adjusting for depression and anxiety. In within-group analyses, physical disability inversely correlated with stria terminalis/fornix and medial forebrain bundle FA values; illness duration negatively correlated with stria terminalis/fornix white matter integrity. A FND symptom severity composite score did not correlate with FA in patients.

Conclusions
In this first DTI study of mixed FND, microstructural differences were observed in limbic and associative tracts implicated in salience, defensive behaviors, and emotion regulation. These findings advance our understanding of neurocircuit pathways in the pathophysiology of FND.

Paywall, https://www.cambridge.org/core/jour...al-disorder/83DE1499B3E6EF3FEE6A195EBE1F47B6#
Scihub, https://sci-hub.se/10.1017/S0033291719003386

 

[rvallee]

The level of confusion in FND is mind-boggling. It's built on the premise of there being no abnormal physiology and here it is discussing observed physiological abnormalities. It's explicitly defined as aka conversion disorder and hysteria, purely psychogenic.

Just call it neuropsychiatry, no? Or just plain neurology, since the only involvement of psychiatry is the pointing at of illness behavior, a normal thing in ill people, and declaring it abnormal out of a belief that everything is otherwise normal. As it is it makes as much sense as a group of HIV deniers doing research on HIV. Make up your damn mind, maybe? Is self-consistency overrated? It seems like a basic requirement.

 

[Mithriel]

These findings advance our understanding of neurocircuit pathways in the pathophysiology of FND.

Yes, FND is claimed to be neurological problems with no physical deficits found, but now they are busy finding the physical signs in the brain for this "disease" that is purely psychological and behavioural.

Doublethink is to weak a word to describe the mentality of these people. The cruelty they rain on their patients is beyond belief.

 

[rvallee]

Yes, FND is claimed to be neurological problems with no physical deficits found, but now they are busy finding the physical signs in the brain for this "disease" that is purely psychological and behavioural.

Doublethink is to weak a word to describe the mentality of these people. The cruelty they rain on their patients is beyond belief.

To be fair, if that's what's happening, I'm all up for people trying to find the actual causes, point at them and say "see, there's your physiology, now drop the damn magical psychology and get on with it".

FND has been accepted without evidence because it's hysteria in disguise, the belief was already established and all they did is add a fake mustache to it. The only way to dethrone the belief system will be to provide evidence that the location may have been generally right, but the mechanism is something else entirely. Just like with peptic ulcers. I have no doubt that there are genuine scientists working on those things, they just tend to have less impact because they don't make assertions without evidence, unlike those who promote things like FND as if it were as validated as general relativity.

The fact that there's no cheap attempt to sprinkle in some random loose psychosocial "association" makes it possible that's the case here. I don't think FND has any value but right now it has enough influence to negatively impact research and clinical practice so it's kind of necessary to work on falsifying it. Shouldn't have to but magical thinking gonna magical think.

 

[NelliePledge]

I would love it if they have decent evidence of physical differences.

 

[Mithriel]

Conclusions
In this first DTI study of mixed FND, microstructural differences were observed in limbic and associative tracts implicated in salience, defensive behaviors, and emotion regulation. These findings advance our understanding of neurocircuit pathways in the pathophysiology of FND.

This is what worries me. The mixed FND implies that all the categories they call FND, ME to IBS and everything inbetween, shares a common pathology of emotional disorder so it is a confirmation they are right to treat them all as conversion disorder.

They are saying that the only thing wrong with the brain is in the psychological workings. I am allowing my prejudices here but if it is emotional then it is because of the stigma and strain of having the diagnosis of FND that they have found, a consequence not a cause. I just cannot see how a dropped foot, seizures and diarrhoea can have a similar brain disorder.

I would love it if they have decent evidence of physical differences.

I see what you mean, but that is only good if they then decide that is proof it is not a hysterical disorder. We already have the problem that they have "proved" FND exists because there are signs for it. This paper claims that all the patients had positive signs for FND; that is it is no longer seen as a disease of exclusion. That alone makes it much harder to fight against.

If they keep producing papers about brain findings that show physical signs of emotional disorders we will be in the same situation as ME, forced to a treatment that cannot help because it is based on a false premise.

The prospect really frightens me.

 

[NelliePledge]

But if there’s physical evidence it can’t be functional in their sense anymore can it? I thought Functional means without evidence of physical abnormality?

 

[Jonathan Edwards]

But if there’s physical evidence it can’t be functional in their sense anymore can it? I thought Functional means without evidence of physical abnormality?

I think functional implies that there is no structural change but there can be shifts in physical activities.
And in reality those shifts must reflect subtle structural change at some level. The talk here is of microstructure change. Diffusion tensor imaging measures shifts in water flow I think and thereby indicates patterns of cactive signal sending along connections but I do not know the detail.

But I agree that there seems to be some circularity or ambiguous definition here.

I also think it is suggestive of blinkered thinking that they want to suggest that the structural features that they have found operate through 'psychological' pathways. Why not through low level pathways that do not fall under what we would call psychological?

 

[Hoopoe]

Like the CBT/GET enthusiasts, they are working backwards from established dogma, trying to prove it is true, rather than trying to find out what is actually true.

 

[Mithriel]

Jonathan Edwards says

I also think it is suggestive of blinkered thinking that they want to suggest that the structural features that they have found operate through 'psychological' pathways. Why not through low level pathways that do not fall under what we would call psychological?

This hits the nail on the head. They have now got research that shows signs that can be found in a straightforward neurological examination which indicates FND in the same way MS can be shown. Now they are showing changes in the structure of the brain using up to date technology which is specific to their diagnosis of conversion disorder. They are moving hysteria into the modern world.

Most doctors have been told that psychology causes neurological disease and just accept it the way they would accept something about thyroid disease from an endrocrinologist. They are too busy with their own concerns to wonder exactly why psychology needs to be invoked when physical signs are present.

The one thing they will not do is read beyond the conclusions in a paper and chase up references. We may know how dodgy the research is and that references do not always support how they are used in a paper but most medical people will assume that everything is accurate and the claims made are true.

When psychological treatment does not work it will be put down to patients refusing to admit they have a psychological problem. We all know how that works for ME.

Their theories are triumphantly true, their careers made, lots of research money and clinic jobs, no need to pay money to help patients who won't take their medicine; none of the aids and adaptations "genuine" neurological patients get and as for benefits ...

 

[Snow Leopard]

I'm getting very bored with studies that attempt to measure something as a biomarker, but consistently fail to state the sensitivity and specificity of that association.

Thirty-two subjects with FND (22 women, 10 men; mean age = 40.9 ± 13.1; average illness duration = 3.5 ± 4.5 years) were recruited from the Massachusetts General Hospital FND Clinic

Given the overlap across the FND spectrum (Perez et al., 2015), we used a transdiagnostic approach that included clinicallyestablished functional movement disorders [n = 17; five tremor, five gait, one jerky movements, one paroxysmal truncal/head movements, five mixed (including one with functional dystonia)], functional weakness (n = 13), and documented (n = 13) or clinically-established (n = 1) PNES. Eleven of 32 subjects had mixed phenotypes.

Summary:

Patients with FND compared to controls showed white matter differences originating from the following brain areas: bilateral amygdala, insula, parahippocampal gyri, temporal poles, precentral gyri, superior parietal lobules, putamen, periaqueductal gray, midbrain, pons and right hippocampus, entorhinal cortex, and the isthmus of the cingulate gyrus. Based on link-level analyses, seven fiber bundles showed reduced FA in patients with FND compared to controls: (1) stria terminalis/fornix; (2) medial forebrain bundle/PAG projections; (3) uncinate fasciculus; (4) extreme capsule; (5) cingulum bundle; (6) corpus callosum; and (7) striatal-postcentral gyrus projections (see Fig. 1). See online Supplementary Fig. S1 for a description of all links surviving multiple comparison correction. No statistically significant links with higher FA in FND v. controls were found

An unanswered question relates to how to optimally contextualize the fiber bundle differences identified in this study, particularly whether the findings relate to disease mechanisms, predisposing vulnerabilities, psychiatric comorbidities, and/or compensatory processes (Begue, Adams, Stone, & Perez, 2019). While studies with larger sample sizes and longitudinal neuroimaging data collection are needed to clarify these issues, it is notable that the integrity of two specific fiber tracts, the stria terminalis/fornix and the medial forebrain bundle, were implicated in patient-reported physical disability and illness duration.

All of this is merely of 'suggestive' quality evidence, until replicated specifically compared to other illnesses.