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Original research
Relationship between intrinsic network connectivity and psychiatric symptom severity in functional seizures
  1. Adam M Goodman1,
  2. Pranav Kakulamarri1,2,
  3. Rodolphe Nenert1,
  4. Jane B Allendorfer1,
  5. Noah S Philip3,4,
  6. Stephen Correia3,4,
  7. W Curt LaFrance Jr3,4,5,6,
  8. Jerzy P Szaflarski1
  1. 1 Neurology, The University of Alabama at Birmingham, Birmingham, Alabama, USA
  2. 2 Psychology, The University of Alabama at Birmingham, Birmingham, Alabama, USA
  3. 3 RR&D Center for Neurorestoration and Neurotechnology, VA Providence Healthcare System, Providence, Rhode Island, USA
  4. 4 Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA
  5. 5 Neurology, Alpert Medical School of Brown University, Providence, RI, USA
  6. 6 Division of Neuropsychiatry and Behavioral Neurology, Rhode Island Hospital, Providence, Rhode Island, USA
  1. Correspondence to Dr Adam M Goodman; amgood{at}; Dr Jerzy P Szaflarski; jszaflarski{at}


Background Traumatic brain injury (TBI) may precipitate the onset of functional seizures (FSs). Many patients with FS report at least one prior TBI, and these patients typically present with more severe psychiatric comorbidities. TBI and psychopathology are linked to changes in neural network connectivity, but their combined effects on these networks and relationship to the effects of FS remain unclear. We hypothesised that resting-state functional connectivity (rsFC) would differ between patients with FS and TBI (FS+TBI) compared with TBI without FS (TBI only), with variability only partially explained by the presence of psychopathology.

Methods Patients with FS+TBI (n=52) and TBI only (n=54) were matched for age and sex. All participants completed psychiatric assessments prior to resting-state functional MRI at 3 T. Independent component analysis identified five canonical rsFC networks related to emotion and motor functions.

Results Five linear mixed-effects analyses identified clusters of connectivity coefficients that differed between groups within the posterior cingulate of the default mode network, insula and supramarginal gyrus of the executive control network and bilateral anterior cingulate of the salience network (all α=0.05, corrected). Cluster signal extractions revealed decreased contributions to each network for FS+TBI compared to TBI only. Planned secondary analyses demonstrated correlations between signal and severity of mood, anxiety, somatisation and global functioning symptoms.

Conclusions These findings indicate the presence of aberrant connectivity in FS and extend the biopsychosocial network model by demonstrating that common aetiology is linked to both FS and comorbidities, but the overlap in affected networks varies by comorbid symptoms.


Data availability statement

Data are available upon reasonable request. Data will be available at (Neuroimaging Biomarker For Seizures, ID#398) after the terminal date of an embargo period or are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request. Data will be available at (Neuroimaging Biomarker For Seizures, ID#398) after the terminal date of an embargo period or are available upon reasonable request.

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  • AMG and PK contributed equally.

  • Contributors AMG and PK analysed and interpreted the data and drafted and revised the manuscript for intellectual content. RN, JBA, NSP, SC, WCL and JPS revised the manuscript for intellectual content. JBA, WCL and JSP developed, designed and conceptualised the study. WCL and JSP obtained funding support for the study. AMG is the guarantor of the study.

  • Funding U.S. Department of Defense (W81XWH-17-1-0619).

  • Disclaimer Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the University of Alabama at Birmingham, Brown University or Rhode Island Hospital. This material is the result of work supported with resources and the use of facilities at the VA Providence Healthcare System, Providence RI. The contents do not represent the views of the US Department of Veterans Affairs, Department of Defense or the US government.

  • Competing interests AMG was funded by US Department of Defense (grant W81XWH-17-1-0619) and National Institutes of Health (NIH) (grant R01HD102723). RN, SC, PK has no conflicts to report. NSP received clinical trial support from Wave Neuro and Neurolief through Veterans Affairs contracts. JBA was funded by the US Department of Defense (W81XWH-17-1-0619), the state of Alabama 'Carly’s Law', the Evelyn F. McKnight Brain Institute at University of Alabama at Birmingham and NIH (R01HD102723 (PI)) and has served as a consultant for LivaNova Inc. WCL Jr. Dr. LaFrance served on the editorial boards of Epilepsia, Epilepsy & Behavior; Journal of Neurology, Neurosurgery and Psychiatry, and Journal of Neuropsychiatry and Clinical Neurosciences; received editor’s royalties from the publication of Gates and Rowan’s Nonepileptic Seizures, 3rd ed. (Cambridge University Press, 2010) and 4th ed. (2018); received author’s royalties for Taking Control of Your Seizures: Workbook and Therapist Guide (Oxford University Press, 2015); received research support from the Department of Defense (DoD W81XWH-17-0169), NIH (NINDS 5K23NS45902 (PI)), Providence VAMC, Center for Neurorestoration and Neurotechnology, Rhode Island Hospital, the American Epilepsy Society, the Epilepsy Foundation, Brown University and the Siravo Foundation; served on the Epilepsy Foundation New England Professional Advisory Board, the Functional Neurological Disorder Society Board of Directors and the American Neuropsychiatric Association Advisory Council; received honoraria for the American Academy of Neurology Annual Meeting; served as a clinic development consultant at University of Colorado Denver, Cleveland Clinic, Spectrum Health, Emory University, Oregon Health Sciences University and Vanderbilt University; and provided medicolegal expert testimony. JPS is funded by NIH, NSF, DoD, State of Alabama, Shor Foundation for Epilepsy Research, UCB Pharma, NeuroPace, Greenwich Biosciences, Biogen, Xenon Pharmaceuticals and Serina Therapeutics; served on consulting/advisory boards for Greenwich Biosciences, NeuroPace, Serina Therapeutics, LivaNova, UCB Pharma, iFovea, AdCel Biopharma LLC, and Elite Medical Experts LLC and served as an editorial board member for Epilepsy & Behavior, Journal of Epileptology (associate editor), Epilepsy & Behavior Reports (associate editor), Journal of Medical Science, Epilepsy Currents (contributing editor) and Folia Medica Copernicana.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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