Reduced microstructural white matter integrity is associated with the severity of physical symptoms in [FND], 2025, Gninenko, Müller, Aybek

SNT Gatchaman

SNT Gatchaman

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Reduced microstructural white matter integrity is associated with the severity of physical symptoms in functional neurological disorder
Gninenko; Müller; Aybek

BACKGROUND
Functional neurological disorder (FND) is linked to functional changes in brain networks without an underlying brain lesion. However, the dichotomy between functional and structural changes has been challenged by research suggesting that not only functional but also anatomical alterations in the gray and white matter may underlie a subset of symptoms. This study aimed to characterize white matter microstructural integrity and its association with patient-reported and clinician-rated physical symptoms’ severity in a large sample of FND patients.

METHODS
Diffusion-weighted imaging data were collected from 85 FND patients with mixed symptoms and 75 healthy controls (HCs), together with illness duration, clinician-rated (S-FMDRS & CGI), and patient-reported (SF-36) symptom severity. Microstructural integrity was computed based on probabilistic tractography using the Desikan-Killiany parcellation.

RESULTS
Compared to HCs, patients with FND presented widespread reduced microstructural integrity stemming from regions such as the right lateral orbitofrontal cortex, insula, putamen, and superior temporal regions. After adjusting for depression and anxiety, these differences were no longer significant. Within-group analysis revealed that reduced microstructural integrity, particularly in the left precuneus and left superior parietal cortex, was strongly correlated with both patient-reported and clinician-evaluated severity of physical symptoms in FND patients.

CONCLUSION
Patients with FND present widespread reduced microstructural integrity in the brain, predominantly originating from temporoparietal, paralimbic and associated regions involved in emotion regulation and body awareness. These changes seem to be partly explained by comorbid mood disorders and the severity of physical symptoms, suggesting a plasticity phenomenon rather than trait biomarkers, which warrants further investigation in longitudinal study designs.

HIGHLIGHTS
• Widespread reduced white matter integrity found in FND patients vs healthy controls.

• Physical symptom severity in FND patients linked to lower microstructural integrity.

• Between-group differences explained by comorbid anxiety and depression symptoms.

Link (NeuroImage: Clinical) [Open Access]
 
abstract said:
Physical symptom severity in FND patients linked to lower microstructural integrity.
• Between-group differences explained by comorbid anxiety and depression symptoms.
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abstract said:
Compared to HCs, patients with FND presented widespread reduced microstructural integrity stemming from regions such as the right lateral orbitofrontal cortex, insula, putamen, and superior temporal regions. After adjusting for depression and anxiety, these differences were no longer significant.
Click to expand...
abstract said:
These changes seem to be partly explained by comorbid mood disorders and the severity of physical symptoms, suggesting a plasticity phenomenon rather than trait biomarkers, which warrants further investigation in longitudinal study designs.
Click to expand...

All the fancy tech and yet the researchers still can't seem to think clearly about association and causation.

People with more severe symptoms are more likely to score worse on surveys claimed to assess depression and anxiety. Part of that is that the surveys can't properly differentiate debilitating chronic illness from depression and anxiety. Part of it is that is that having a debilitating chronic illness that reduces a person's ability to earn a living and do the things they like to do makes people, at least some of the time, sad and worried.
 
The available DWI data from a previously published cohort (Weber et al., 2023, Weber et al., 2024) of 85 FND patients diagnosed with motor (International Classification of Diseases, Tenth Revision [ICD-10] code F44.4) and sensory (F44.6) symptoms, functional seizures (F44.5), mixed symptom type (F44.7), and persistent postural-perceptual dizziness (PPPD, ICD-11 code AB32), as well as from 75 age- and sex-matched HCs, were further preprocessed.

The FND diagnosis was established according to DSM-5 (American Psychiatric Association et al., 2013) and positive signs (Stone and Carson, 2015) by experienced board-certified neurologists from the University Hospital Inselspital (Bern, Switzerland).
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I still don’t understand how they get away with diagnosing a «functional» disorder through positive signs.
Anxiety and depression were assessed using the State-Trait Anxiety Inventory (STAI, both trait and state) (Spielberger, 2010) and Beck’s Depression Inventory (BDI) (Beck et al., 1996), respectively.
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@Hutan has already elaborated on the issues with STAI in other studies:
Hutan said:
the questions about trait anxiety in the State/Trait Anxiety Inventory include:
Questions that a person with fatigue will score poorly on e.g.
  • I feel rested;
  • I tire easily;
Questions that a person with a chronic illness that prevents them from living the life they want is likely to score poorly on e.g.
  • I felt satisfied with myself,
  • I feel like a failure,
  • I am happy,
  • I lack self-confidence,
  • I feel inadequate,
  • I feel content
Questions that are legitimate concerns for someone who is struggling to earn a living e.g.
  • I feel that difficulties are piling up
Questions about anxiety e.g.
  • I worry too much over something
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The same goes for BDI. I won’t bother listing the questions, but they can be found here:
https://www.ismanet.org/doctoryourspirit/pdfs/Beck-Depression-Inventory-BDI.pdf
 
The right TPJ is discussed.

At the functional level, hypoactivity of the right TPJ and reduced functional connectivity with primary sensorimotor areas have also been demonstrated, which may explain body awareness disturbances in patients with FND. These findings on the implication of TPJ as an origin of reduced white matter integrity with the likely involvement of major association tracts such as the arcuate fasciculus, inferior longitudinal fasciculus, and superior longitudinal fasciculus, may further contribute to the understanding of the neuroanatomical basis for the sense of agency deficits observed in FND patients.
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Again, where is the functional bit in the finding of altered structures?

There is now only one way out of this for the medical profession: completely drop the whole FND category and concept, fire those responsible for inflicting this cruel travesty on the world, and start again from scratch with a whole new team.
 
Utsikt said:
I still don’t understand how they get away with diagnosing a «functional» disorder through positive signs.
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I think David Tuller's written about that.
AFAI Remember they created a clinical construct saying it happens because software problems in the brain, claiming they could differentiate it with positive signs (which are pretty subjective and rely on opaque things like "neurological expertise")

It's done like this so the concept is by definition "valid". In that there can't be any studies disproving the validity of the positive signs since the concept is defined by the positive signs.

The logic ends up looking suspiciously like:
FND exists because positive signs show it. Positive signs show FND because FND exists as defined by these signs.

Which in a sense is okay logic if FND is a clinical category. But since the whole concept assumes an unproven mechanism and treats people as if they had this mechanism with no validiy behind it, its not okay.
 
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