Neuroimaging evidence of structural and network disruptions in adolescents with conversion disorder with seizures, 2025, Dhanik et al.

[SNT Gatchaman]

Neuroimaging evidence of structural and network disruptions in adolescents with conversion disorder with seizures
Kalpana Dhanik; Amit Arya; Vivek Agarwal; Uttam Kumar

BACKGROUND
This study investigated structural and network-level brain alterations in adolescents with conversion disorder with attacks of seizures (CD/FS), focusing on stage-specific differences across acute and persistent presentations.

METHODS
Sixty adolescents with CD/FS (26 acute-stage, 34 persistent-stage) and 60 age-matched controls underwent 3 T MRI. Voxel-based morphometry (VBM), source-based morphometry (SBM), and connectogram analyses were used to assess grey and white matter (GM and WM) alterations. Correlations with dissociative symptoms (DES scores) and age were evaluated.

RESULTS
Compared to controls, adolescents with CD/FS showed significant reductions in total GM and WM volumes. Acute-stage CD/FS was marked by localized GM increases in the mid-temporal poles and focal WM disruptions, while persistent-stage CD/FS exhibited widespread structural abnormalities, including volume reductions in the precuneus, posterior cingulate cortex, cerebellum, and cingulum. SBM revealed GM alterations in the hippocampus, lingual gyrus, putamen, and pallidum, along with WM changes in the midbrain and precuneus. Connectogram analysis showed progressive network disintegration—acute-stage CD/FS demonstrated localized disruptions in salience (SN) and default mode networks (DMN), whereas persistent-stage CD/FS showed widespread negative connectivity across SN, DMN, limbic, and executive networks.

CONCLUSIONS
Findings indicate that CD/FS in adolescents progresses from localized to widespread structural and network dysfunction. These findings highlight the importance of early identification of stage-specific brain network alterations in adolescents with functional seizures, which may support future efforts to develop prognostic markers and inform individualized clinical approaches.

HIGHLIGHTS
• GM and WM changes progress from focal (acute) to widespread (persistent) in CD/PNES.

• Network disconnections intensify in SN, DMN, and limbic circuits with chronicity.

• SBM reveals distinct GM and WM components altered in CD/PNES.

• GM volume correlates with DES; WM volume shows age-related decline.

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[Utsikt]

Findings indicate that CD/FS in adolescents progresses from localized to widespread structural and network dysfunction.

Not so functional after all then?

 

[SNT Gatchaman]

Functional seizures (FS) previously referred to as psychogenic nonepileptic seizures (PNES) or conversion disorder with seizures (CD) constitute a prominent subset of functional neurological disorders (FND), characterized by seizure-like episodes that occur in the absence of epileptiform activity on electroencephalography (EEG).

A study by Loewenberger et al. evaluated public preferences across multiple diagnostic labels and found that terms such as functional seizures and functional nonepileptic attacks (FNEA) were among the most preferred and least offensive, whereas terms like pseudoseizures, conversion disorder, and hysteria were rated as highly stigmatizing and associated with lower expectations for psychological recovery. These findings support the adoption of “functional seizures” in clinical practice due to its neutrality, descriptive clarity, and greater acceptability. Despite these definitional and terminological advancements, FS remains underrecognized in pediatric populations, where diagnostic delays and mislabeling often result in iatrogenic harm.

While historically framed within a psychogenic model, emerging evidence implicates structural and functional brain abnormalities in CD/FS, particularly in regions involved in emotion regulation, sensory processing, and motor control. Structural MRI studies in adults with FS have consistently shown GM reductions in the anterior cingulate cortex (ACC), prefrontal cortex, temporal lobes, motor areas, basal ganglia, and cerebellum [14–17]. These reductions suggest impaired top-down regulatory mechanisms and altered sensorimotor integration. […] WM disruptions have also been well documented. DTI highlights reduced fractional anisotropy (FA) in key fronto-limbic tracts, including the corpus callosum, cingulum bundle, and uncinate fasciculus, reflecting impaired interhemispheric transfer and emotion-sensory integration [20–24].

From results. DES is the Dissociative Experiences Scale.

Adolescents with CD/FS exhibited significantly reduced total grey matter (GM) volume (506 ± 13 mm 3 , mean ± SD) compared to healthy controls (551 ± 97 mm 3 , mean ± SD; t(59) = –2.93, p < 0.01). White matter (WM) volume was also significantly lower in the CD/FS group (422 ± 81 mm 3 , mean ± SD) compared to controls (503 ± 125 mm3 , mean ± SD; t(59) = –2.11, p = 0.03). A significant positive correlation was observed between DES scores and GM volume (r = 0.48, p < 0.001), indicating that higher dissociative symptoms were associated with increased GM volume in specific regions. GM volume also positively correlated with age (r = 0.43, p = 0.02). Conversely, WM volume showed a significant negative correlation with DES scores (r = –0.23, p = 0.03), suggesting reduced white matter integrity with greater dissociative symptomatology.

GM volume positively correlated with dissociative symptoms and age, whereas WM volume negatively correlated with dissociation, suggesting a dual mechanism involving compensatory hypertrophy in select cortical regions and diminished integrity of connecting pathways.

 

[forestglip]

Adolescents with CD/FS exhibited significantly reduced total grey matter (GM) volume

A significant positive correlation was observed between DES scores and GM volume (r = 0.48, p < 0.001)

So opposite correlation for grey matter within the cases as opposed to between cases and controls?

 

[SNT Gatchaman]

The CD/FS and control groups were statistically matched across multiple lifestyle dimensions, including socio-cultural structure, economic status, access to goods and services, health indices, and educational background. This rigorous matching reinforces the interpretation that the observed brain differences are more likely attributable to the pathophysiology of functional seizures rather than disparities in upbringing or environmental deprivation. These relationships also support the idea that in adolescents, structural neuroplasticity may initially emerge as an adaptive response to psychosocial stress but may later become maladaptive, thereby contributing to disease progression.

So if they are rigorously matched, what is the other factor that causes FND to develop in cases but not controls? It sounds like they're handwaving away as "sometimes it just be like that".

 

[Turtle]

Can seizures be pathophysiologycal and functional at the same time?