Corticolimbic fast-tracking: enhanced multimodal integration in functional neurological disorder
Open accessAbstract
Objective: Some individuals with functional neurological disorder (FND) exhibit motor and affective disturbances, along with limbic hyper-reactivity and enhanced motor-limbic connectivity. Given that the multimodal integration network (insula, dorsal cingulate, temporoparietal junction (TPJ)) is implicated in convergent sensorimotor, affective and interoceptive processing, we hypothesised that patients with FND would exhibit altered motor and amygdalar resting-state propagation to this network. Patient-reported symptom severity and clinical outcome were also hypothesised to map onto multimodal integration areas. Methods: Between-group differences in primary motor and amygdalar nuclei (laterobasal, centromedial) were examined using graph-theory stepwise functional connectivity (SFC) in 30 patients with motor FND compared with 30 healthy controls. Within-group analyses correlated functional propagation profiles with symptom severity and prospectively collected 6-month outcomes as measured by the Screening for Somatoform Symptoms Conversion Disorder subscale and Patient Health Questionnaire-15 composite score. Findings were clusterwise corrected for multiple comparisons. Results: Compared with controls, patients with FND exhibited increased SFC from motor regions to the bilateral posterior insula, TPJ, middle cingulate cortex and putamen. From the right laterobasal amygdala, the FND cohort showed enhanced connectivity to the left anterior insula, periaqueductal grey and hypothalamus among other areas. In within-group analyses, symptom severity correlated with enhanced SFC from the left anterior insula to the right anterior insula and TPJ; increased SFC from the left centromedial amygdala to the right anterior insula correlated with clinical improvement. Within-group associations held controlling for depression, anxiety and antidepressant use. Conclusions: These neuroimaging findings suggest potential candidate neurocircuit pathways in the pathophysiology of FND.
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Heightened arousal is linked to defensive behaviours driven by the periaqueductal grey, such as tonic immobility and fight or flight responses, which are behavioural programmes that share overlapping semiological features with functional seizures.
“Additionally, heightened arousal is linked to defensive behaviours driven by the periaqueductal grey, such as tonic immobility and fight or flight responses-behavioural programmes that share overlapping semiological features with functional seizures.45,[171][172][173][174]”
From A new science of emotion: implications for functional neurological disorder (2022) · cites this paper as [172]
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- Authors
- Diez, I., Ortiz-Terán, L., Williams, B., Jalilianhasanpour, R., Ospina, J. P., Dickerson, B. C., Keshavan, M. S., LaFrance Jr, W. C., Sepulcre, J., & Perez, D. L.
- Affiliations
- Harvard University (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Perez, David L
- ORCID
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2019-03-08
- Volume
- 90
- Issue
- 8
- Pages
- 929-938
- ISSN
- 0022-3050 (ISSN-L)
- 1468-330X
- PMC
- PMC6625895
- OpenAlex
- W2920853899
- Semantic Scholar
- 59828e3cdf3b1fd5e5b458161109eca010346c35
- Cited by
- 99
- References
- 56
- Citations by year
- 2026: 17 · 2025: 17 · 2024: 15 · 2023: 7 · 2022: 15 · 2021: 8 · 2020: 14 · 2019: 6
- FWCI
- 8.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- TECNALIA Publications (Fundación TECNALIA Research & Innovation) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Basque Country Government Post-Doctoral Research Fellowship
- National Institute of Health (S10RR023043)
- Massachusetts General Hospital Physician-Scientist Development Award
- National Institute of Mental Health (K23MH111983-02)
- Sidney R. Baer, Jr. Foundation
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- conversion disorder, resting-state functional connectivity, anterior insula, temporoparietal junction, middle cingulate cortex, amygdala, centromedial amygdala, symptom severity, clinical outcomes, somatoform symptoms
- MeSH terms
- Adult, Amygdala, Brain, Conversion Disorder, Female, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Membrane Potentials, Motor Cortex, Neural Pathways, Putamen, Surveys and Questionnaires, Severity of Illness Index, Case-Control Studies, Neuroimaging
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