Neuroplastic changes in patients with functional seizures following neurobehavioral therapy, 2025, Sharma et al.

[SNT Gatchaman]

Neuroplastic changes in patients with functional seizures following neurobehavioral therapy
Sharma; Allendorfer; Correia; Gaston; Goodman; Grayson; Philip; LaFrance; Szaflarski

Given the high prevalence of functional neurological symptom disorder and its negative effects on the individual, family, and society, the development of interventions to treat it—including the subtype of functional seizures (FS)—is critical. Although we have limited understanding of the neurobiological effects of neurobehavioral therapy (NBT), studies indicate that NBT reduces seizures and improves psychological comorbidities in FS.

In this study, healthy adults (N = 33) and patients with a history of TBI with (TBI-FS; N = 50) and without FS (TBI-only; N = 50) underwent magnetic resonance imaging (MRI) at 3 T approximately 12 weeks apart. TBI-FS participants underwent up to 12 sessions of NBT between scans. Structural MRI data were analyzed using voxel-based morphometry. A voxelwise repeated measures ANOVA tested changes in grey matter volume (GMV) between groups over time.

Following treatment with NBT, TBI-FS participants showed a 1.23 % GMV increase in the left inferior and middle temporal gyri (pFWE < 0.05) along with a 35.78 % reduction in seizure events and decrease in depressive (p < 0.001) and anxiety (p = 0.01) symptoms. Left temporal GMV increases were directly associated (p = 0.04, r = 0.26) with improvements in overall psychological, social, and occupational functioning (p < 0.001).

We observed structural brain changes within the left inferior temporal gyrus following NBT that correspond to functional and psychological improvements in patients with TBI-FS. This work highlights the need for further research into the neurobiological effects of NBT, building on the relationship between NBT and brain plasticity and demonstrating putative targets for interventions.

HIGHLIGHTS
• Neurobehavioral therapy (NBT) reduces functional seizures.

• No previous study has investigated structural brain changes underlying NBT’s effects.

• In this study, left temporal grey matter volume increased in patients with FS after NBT.

• Gray matter increases were linked to better psychological health.

• NBT may boost brain plasticity in patients with functional seizures.

Link (NeuroImage: Clinical) [Open Access]

 

[SNT Gatchaman]

Functional seizures (FS), (also called psychogenic nonepileptic (PNES) or dissociative seizures), present with a complex array of physical, cognitive, and psychological symptoms along with various psychiatric features. The past two decades have witnessed a significant evolution in our understanding of FS and other subtypes of functional neurological disorder (FND), leading to improved recognition, diagnosis, and treatment across multiple medical specialties. […] As a result, behavioral and neuroimaging studies of FS have revealed a spectrum of structural, functional, genetic, and neuroinflammatory abnormalities in brain regions crucial for inhibition, executive control, emotion regulation, and sensorimotor processing.

Overall, the studies conducted to date have provided valuable information about the neuromorphometric changes associated with TBI-FS. However, further research is needed to determine the exact cause of these structural abnormalities and whether targeted therapies fulfill neurorestorative or neuroregenerative functions.

The present study addressed an important knowledge gap by examining structural brain changes following NBT treatment in individuals with TBI-FS.

This study is the first to our knowledge to demonstrate structural changes in patients with FS following a psychotherapy intervention, specifically NBT.

The post-NBT GMV increases observed in these regions may therefore represent enhancement of neural infrastructure supporting improved cognitive control, executive function, and emotional self-regulation—processes that NBT directly targets. Since these temporal gyri are important constituents of the neural networks that support these processes, their structural enhancement may have cascading effects on broader neural systems involved in symptom management and functional improvement in patients with FS.

Given that both TBI and FS have been associated with altered neuroinflammatory profiles, the post-NBT GMV increases observed in the present study could partly reflect normalization of glial cell function and morphology.

Stress reduction components of NBT may particularly impact these processes, as chronic stress and elevated glucocorticoid levels are known to influence glial cell function and neuroinflammatory signaling. Therefore, these cellular-level changes could provide a mechanistic basis for the structural alterations found in the present study.

Together, these epigenetic processes create a molecular bridge between psychotherapy interventions and MRI-detectable structural brain changes. This epigenetically-mediate environment may support structural recovery in regions associated with emotional processing and cognitive control, as seen in the present study. Future research investigating these interconnected phenomena could reveal the specific mechanisms underlying NBT-induced neuroplasticity and even potentially identify biomarkers of treatment response, thus advancing the ongoing development of targeted interventions for patients FS and other subtypes of FND.

 

[SNT Gatchaman]

FND researchers might have crossed the structural Rubicon. Not sure where that leaves the "it's software not hardware" people.

The authors did note the absence of a control group. But they're convinced nonetheless.

Limitations of this study include the following. The absence of a TBI+FS control group that did not receive NBT is a limitation of the current study. While the TBI-only group received treatment with SMC, the identified brain changes in the TBI+FS cohort attributable to NBT could be assessed in future studies by recruiting a TBI+FS group that does not receive the study intervention (however, since there is no longer equipoise between NBT and no treatment, an active control study would need to be designed).

 

[Hutan]

I'm not sure if we just have a bad batch of studies today or if I am just grumpy. But, for goodness sake.

A mean 1.23% change in the grey matter of a bit of the brain, in imaging taken 3 months apart? That's virtually nothing.
This is what AI has to say about that, and I support it:

A 1% increase in brain volume over two MRIs is generally not considered significant in most research contexts. While any change is a change, such small fluctuations are often attributed to normal variations in factors like hydration, blood pressure, and the inherent precision limitations of MRI measurements. Larger changes, often exceeding 5%, are more likely to indicate meaningful changes or a need for further investigation.

And, yeah, NO CONTROL. There's a lot going on in this study, but most of it is window dressing. A lot of action but without a relevant control we can't actually know if the observed changes have anything to do with the treatment.

There's a lot more that could be said, even just based on the abstract.

 

[Sean]

As a result, behavioral and neuroimaging studies of FS have revealed a spectrum of structural, functional, genetic, and neuroinflammatory abnormalities in brain regions crucial for inhibition, executive control, emotion regulation, and sensorimotor processing.​

Doesn't sound functional to me.

 

[Jonathan Edwards]

A mean 1.23% change in the grey matter of a bit of the brain, in imaging taken 3 months apart?

Sounds as if it might be a calibration artefact due to shifting the pillow in the MRI machine. Without controls ... And p<0.05. I cannot be bothered to see if that is appropriately corrected.

 

[rvallee]

We observed structural brain changes within the left inferior temporal gyrus following NBT that correspond to functional and psychological improvements in patients with TBI-FS

Putting aside the issue of how 'structural' changes doesn't fit with the idea of 'functional' this or that, did they introduce a similar word to correlate, in using correspond, because it means the same thing but avoids the whole "correlation isn't causation"?

One thing is sure is that this 'study' says nothing about the effects of this "NBT" thing because there was no comparison.