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Resting state functional connectivity and structural abnormalities of the brain in acute retarded catatonia: an exploratory MRI study

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Abstract

In this first cross-sectional MRI study in acute catatonia, we compared the resting state whole-brain, within-network and seed (left precentral gyrus)-to-voxel connectivity, as well as cortical surface complexity between a sample of patients in acute retarded catatonic state (n = 15) diagnosed as per DSM-5 criteria and a demographically matched healthy control sample (n = 15). The patients had comorbid Axis-I psychiatric disorders including schizophrenia spectrum disorders and psychotic mood disorders, but did not have diagnosable neurological disorders. Acute retarded catatonia was characterized by reduced resting state functional connectivity, most robustly within the sensorimotor network; diffuse region of interest (ROI)-ROI hyperconnectivity; and seed-to-voxel hyperconnectivity in the frontoparietal and cerebellar regions. The seed (left precentral gyrus)-to-voxel connectivity was positively correlated to the catatonia motor ratings. The ROI–ROI as well as seed-to-voxel functional hyperconnectivity were noted to be higher in lorazepam responders (n = 9) in comparison to the non-responders (n = 6). The overall Hedges’ g effect sizes for these analyses ranged between 0.82 and 3.53, indicating robustness of these results, while the average Dice coefficients from jackknife reliability analyses ranged between 0.6 and 1, indicating fair (inter-regional ROI–ROI connectivity) to perfect (within-sensorimotor network connectivity) reliability of the results. The catatonia sample showed reduced vertex-wise cortical complexity in the right insular cortex and contiguous areas. Thus, we have identified neuroimaging markers of the acute retarded catatonic state that may show an association with treatment response to benzodiazepines. We discuss how these novel findings have important translational implications for understanding the pathophysiology of catatonia as well as for the mechanistic understanding and prediction of treatment response to benzodiazepines.

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Availability of data and material

The data used in this study are available from the corresponding author, upon a reasonable request.

Code availability

SPM, CAT, and Conn functional connectivity toolboxes are freely available at their respective websites.

References

  1. Fink M (2013) Rediscovering catatonia: the biography of a treatable syndrome. Acta Psychiatr Scand 127:1–47. https://doi.org/10.1111/acps.12038

    Article  Google Scholar 

  2. Haroche A, Rogers J, Plaze M et al (2020) Brain imaging in catatonia: systematic review and directions for future research. Psychol Med 50:1585–1597. https://doi.org/10.1017/S0033291720001853

    Article  PubMed  Google Scholar 

  3. Walther S, Stegmayer K, Wilson JE et al (2019) Structure and neural mechanisms of catatonia. Lancet Psychiatry 6:610–619. https://doi.org/10.1016/S2215-0366(18)30474-7

    Article  PubMed  PubMed Central  Google Scholar 

  4. Walther S, Schäppi L, Federspiel A et al (2017) Resting-state hyperperfusion of the supplementary motor area in catatonia. Schizophr Bull 43:972–981. https://doi.org/10.1093/schbul/sbw140

    Article  PubMed  Google Scholar 

  5. Hirjak D, Rashidi M, Kubera KM et al (2020) Multimodal magnetic resonance imaging data fusion reveals distinct patterns of abnormal brain structure and function in catatonia. Schizophr Bull 46:202–210. https://doi.org/10.1093/schbul/sbz042

    Article  PubMed  Google Scholar 

  6. Hirjak D, Kubera KM, Northoff G et al (2019) Cortical contributions to distinct symptom dimensions of catatonia. Schizophr Bull 45:1184–1194. https://doi.org/10.1093/schbul/sby192

    Article  PubMed  PubMed Central  Google Scholar 

  7. Dean DJ, Woodward N, Walther S et al (2020) Cognitive motor impairments and brain structure in schizophrenia spectrum disorder patients with a history of catatonia. Schizophr Res 222:335–341. https://doi.org/10.1016/j.schres.2020.05.012

    Article  PubMed  PubMed Central  Google Scholar 

  8. Yotter RA, Nenadic I, Ziegler G et al (2011) Local cortical surface complexity maps from spherical harmonic reconstructions. Neuroimage 56:961–973. https://doi.org/10.1016/j.neuroimage.2011.02.007

    Article  PubMed  Google Scholar 

  9. Narr KL, Bilder RM, Kim S et al (2004) Abnormal gyral complexity in first-episode schizophrenia. Biol Psychiat 55:859–867. https://doi.org/10.1016/j.biopsych.2003.12.027

    Article  PubMed  Google Scholar 

  10. Narr KL, Thompson PM, Sharma T et al (2001) Three-dimensional mapping of gyral shape and cortical surface asymmetries in schizophrenia: gender effects. AJP 158:244–255. https://doi.org/10.1176/appi.ajp.158.2.244

    Article  CAS  Google Scholar 

  11. Collantoni E, Madan CR, Meneguzzo P et al (2020) Cortical complexity in anorexia nervosa: a fractal dimension analysis. J Clin Med 9:833. https://doi.org/10.3390/jcm9030833

    Article  PubMed Central  Google Scholar 

  12. King RD, Brown B, Hwang M et al (2010) Fractal dimension analysis of the cortical ribbon in mild Alzheimer’s disease. Neuroimage 53:471–479. https://doi.org/10.1016/j.neuroimage.2010.06.050

    Article  PubMed  Google Scholar 

  13. de Miras JR, Costumero V, Belloch V et al (2017) Complexity analysis of cortical surface detects changes in future Alzheimer’s disease converters. Hum Brain Mapp 38:5905–5918. https://doi.org/10.1002/hbm.23773

    Article  Google Scholar 

  14. Hirjak D, Kubera KM, Wolf RC et al (2020) Going Back to Kahlbaum’s Psychomotor (and GABAergic) origins: is catatonia more than just a motor and dopaminergic syndrome? Schizophr Bull 46:272–285. https://doi.org/10.1093/schbul/sbz074

    Article  PubMed  Google Scholar 

  15. Rasmussen SA, Mazurek MF, Rosebush PI (2016) Catatonia: Our current understanding of its diagnosis, treatment and pathophysiology. World J Psychiatry 6:391–398. https://doi.org/10.5498/wjp.v6.i4.391

    Article  PubMed  PubMed Central  Google Scholar 

  16. Suchandra HH, Reddi VSK, Aandi Subramaniyam B et al (2020) Revisiting lorazepam challenge test: clinical response with dose variations and utility for catatonia in a psychiatric emergency setting. Aust N Z J Psychiatry. https://doi.org/10.1177/0004867420968915

    Article  PubMed  Google Scholar 

  17. Sienaert P, Dhossche DM, Vancampfort D et al (2014) A clinical review of the treatment of catatonia. Front Psychiatry. https://doi.org/10.3389/fpsyt.2014.00181

    Article  PubMed  PubMed Central  Google Scholar 

  18. Raveendranathan D, Narayanaswamy JC, Reddi SV (2012) Response rate of catatonia to electroconvulsive therapy and its clinical correlates. Eur Arch Psychiatry Clin Neurosci 262:425–430. https://doi.org/10.1007/s00406-011-0285-4

    Article  PubMed  Google Scholar 

  19. American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders: DSM-5TM, 5th edn. American Psychiatric Publishing Inc, Arlington. https://doi.org/10.1176/appi.books.9780890425596

    Book  Google Scholar 

  20. Bush G, Fink M, Petrides G et al (1996) Catatonia. I. Rating scale and standardized examination. Acta Psychiatr Scand 93:129–136. https://doi.org/10.1111/j.1600-0447.1996.tb09814.x

    Article  CAS  PubMed  Google Scholar 

  21. Northoff G, Koch A, Wenke J et al (1999) Catatonia as a psychomotor syndrome: a rating scale and extrapyramidal motor symptoms. Mov Disord 14:404–416. https://doi.org/10.1002/1531-8257(199905)14:3%3c404::AID-MDS1004%3e3.0.CO;2-5

    Article  CAS  PubMed  Google Scholar 

  22. Bush G, Fink M, Petrides G et al (1996) Catatonia. II. Treatment with lorazepam and electroconvulsive therapy. Acta Psychiatr Scand 93:137–143. https://doi.org/10.1111/j.1600-0447.1996.tb09815.x

    Article  CAS  PubMed  Google Scholar 

  23. Fink M, Taylor MA (2003) Catatonia: a clinician’s guide to diagnosis and treatment. Cambridge University Press, Cambridge. https://doi.org/10.1017/CBO9780511543777

    Book  Google Scholar 

  24. Li X, Morgan PS, Ashburner J et al (2016) The first step for neuroimaging data analysis: DICOM to NIfTI conversion. J Neurosci Methods 264:47–56. https://doi.org/10.1016/j.jneumeth.2016.03.001

    Article  PubMed  Google Scholar 

  25. Whitfield-Gabrieli S, Nieto-Castanon A (2012) Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connect 2:125–141. https://doi.org/10.1089/brain.2012.0073

    Article  PubMed  Google Scholar 

  26. Gaser C, Dahnke R, Kurth K et al. A computational anatomy toolbox for the analysis of structural MRI data. NeuroImage (In review)

  27. Ardekani BA (2018) A new approach to symmetric registration of longitudinal structural MRI of the human brain. bioRxiv. https://doi.org/10.1101/306811 (Published Online First)

    Article  Google Scholar 

  28. Ardekani BA, Bachman AH (2009) Model-based automatic detection of the anterior and posterior commissures on MRI scans. Neuroimage 46:677–682. https://doi.org/10.1016/j.neuroimage.2009.02.030

    Article  PubMed  Google Scholar 

  29. Ardekani BA, Kershaw J, Braun M et al (1997) Automatic detection of the mid-sagittal plane in 3-D brain images. IEEE Trans Med Imaging 16:947–952. https://doi.org/10.1109/42.650892

    Article  CAS  PubMed  Google Scholar 

  30. Behzadi Y, Restom K, Liau J et al (2007) A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. Neuroimage 37:90–101. https://doi.org/10.1016/j.neuroimage.2007.04.042

    Article  PubMed  Google Scholar 

  31. Smith SM, Nichols TE (2009) Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage 44:83–98. https://doi.org/10.1016/j.neuroimage.2008.03.061

    Article  PubMed  Google Scholar 

  32. Glasser MF, Coalson TS, Robinson EC et al (2016) A multi-modal parcellation of human cerebral cortex. Nature 536:171–178. https://doi.org/10.1038/nature18933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sui J, Pearlson G, Caprihan A et al (2011) Discriminating schizophrenia and bipolar disorder by fusing fMRI and DTI in a multimodal CCA + joint ICA model. Neuroimage 57:839–855. https://doi.org/10.1016/j.neuroimage.2011.05.055

    Article  PubMed  Google Scholar 

  34. Sui J, He H, Pearlson GD et al (2013) Three-way (N-way) fusion of brain imaging data based on mCCA+jICA and its application to discriminating schizophrenia. Neuroimage 66:119–132. https://doi.org/10.1016/j.neuroimage.2012.10.051

    Article  PubMed  Google Scholar 

  35. Zou Q-H, Zhu C-Z, Yang Y et al (2008) An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF. J Neurosci Methods 172:137–141. https://doi.org/10.1016/j.jneumeth.2008.04.012

    Article  PubMed  PubMed Central  Google Scholar 

  36. Durlak JA (2009) How to select, calculate, and interpret effect sizes. J Pediatr Psychol 34:917–928. https://doi.org/10.1093/jpepsy/jsp004

    Article  PubMed  Google Scholar 

  37. Wilke M (2012) An iterative jackknife approach for assessing reliability and power of fMRI group analyses. PLoS ONE 7:e35578. https://doi.org/10.1371/journal.pone.0035578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wasserthal J, Maier-Hein KH, Neher PF et al (2020) Multiparametric mapping of white matter microstructure in catatonia. Neuropsychopharmacol 45:1750–1757. https://doi.org/10.1038/s41386-020-0691-2

    Article  Google Scholar 

  39. Northoff G, Steinke R, Czcervenka C et al (1999) Decreased density of GABA-A receptors in the left sensorimotor cortex in akinetic catatonia: investigation of in vivo benzodiazepine receptor binding. J Neurol Neurosurg Psychiatry 67:445–450. https://doi.org/10.1136/jnnp.67.4.445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Nasrallah FA, Singh KKD, Yeow LY et al (2017) GABAergic effect on resting-state functional connectivity: dynamics under pharmacological antagonism. Neuroimage 149:53–62. https://doi.org/10.1016/j.neuroimage.2017.01.040

    Article  CAS  PubMed  Google Scholar 

  41. Hillary FG, Roman CA, Venkatesan U et al (2015) Hyperconnectivity is a fundamental response to neurological disruption. Neuropsychology 29:59–75. https://doi.org/10.1037/neu0000110

    Article  PubMed  Google Scholar 

  42. Staba RJ (2012) Normal and pathologic high-frequency oscillations. In: Noebels J, Avoli M, Rogawski M (eds) Jasper’s basic mechanisms of the epilepsies. National Center for Biotechnology Information, Bethesda

    Google Scholar 

  43. Liu S, Parvizi J (2019) Cognitive refractory state caused by spontaneous epileptic high-frequency oscillations in the human brain. Sci Transl Med. https://doi.org/10.1126/scitranslmed.aax7830

    Article  PubMed  PubMed Central  Google Scholar 

  44. Ungvari GS, Leung CM, Wong MK et al (1994) Benzodiazepines in the treatment of catatonic syndrome. Acta Psychiatr Scand 89:285–288. https://doi.org/10.1111/j.1600-0447.1994.tb01515.x

    Article  CAS  PubMed  Google Scholar 

  45. Yassa R, Iskandar H, Lalinec M et al (1990) Lorazepam as an adjunct in the treatment of catatonic states: an open clinical trial. J Clin Psychopharmacol 10:66–67

    Article  CAS  Google Scholar 

  46. Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Routledge Academic, New York. https://doi.org/10.1016/C2013-0-10517-X

    Book  Google Scholar 

  47. Sawilowsky S (2009) New effect size rules of thumb. J Mod Appl Stat Methods. https://doi.org/10.22237/jmasm/1257035100

    Article  Google Scholar 

  48. Sienaert P, Rooseleer J, De Fruyt J (2011) Measuring catatonia: a systematic review of rating scales. J Affect Disord 135:1–9. https://doi.org/10.1016/j.jad.2011.02.012

    Article  PubMed  Google Scholar 

  49. van der Heijden FMMA, Tuinier S, Arts NJM et al (2005) Catatonia: disappeared or under-diagnosed? PSP 38:3–8. https://doi.org/10.1159/000083964

    Article  Google Scholar 

  50. Stuivenga M, Morrens M (2014) Prevalence of the catatonic syndrome in an acute inpatient sample. Front Psych 5:174. https://doi.org/10.3389/fpsyt.2014.00174

    Article  Google Scholar 

  51. Subramaniyam BA, Muliyala KP, Hari Hara S et al (2019) Prevalence of catatonic signs and symptoms in an acute psychiatric unit from a tertiary psychiatric center in India. Asian J Psychiatr 44:13–17. https://doi.org/10.1016/j.ajp.2019.07.003

    Article  PubMed  Google Scholar 

  52. Chumbley JR, Friston KJ (2009) False discovery rate revisited: FDR and topological inference using Gaussian random fields. Neuroimage 44:62–70. https://doi.org/10.1016/j.neuroimage.2008.05.021

    Article  PubMed  Google Scholar 

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Acknowledgements

We acknowledge the support from NIMHANS for carrying out this research as part of the M.D. dissertation of A.G. We thank Mr. Krishnendu Vyas for assistance with the data acquisition of healthy subjects.

Funding

P.P. acknowledges salary support from the Accelerator Program for Discovery in Brain Disorders using Stem Cells (ADBS) project, funded by the Department of Biotechnology, Government of India (BT/PR17316/MED/31/326/2015). No specific funding was received towards this work.

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Author notes

  1. Pravesh Parekh and Anirban Gozi contributed equally to this work.

Authors and Affiliations

  1. Multimodal Brain Image Analysis Laboratory, National Institute of Mental Health and Neurosciences, Bangalore, 560029, India

    Pravesh Parekh, Anirban Gozi & John P. John

  2. Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, 560029, India

    Pravesh Parekh, Anirban Gozi, Venkata Senthil Kumar Reddi & John P. John

  3. Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bangalore, 560029, India

    Jitender Saini

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  1. Pravesh Parekh
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Contributions

The author contributions are based on Contributor Roles Taxonomy (CRediT) (https://casrai.org/credit/): PP: methodology, software, validation, formal analysis, data curation, writing—original draft, writing—review and editing, and visualization. AG: conceptualization, investigation, data curation, and writing—review and editing. VSKR: conceptualization, resources, writing—review and editing, and supervision. JS: conceptualization, investigation, resources, writing—review and editing, supervision, and project administration. JPJ: conceptualization, methodology, validation, resources, data curation, writing—original draft, writing—review and editing, visualization, supervision, and project administration.

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Correspondence to John P. John.

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The authors report no competing interests.

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The study was approved by the Institute ethics committee (NIMH/DO/EHTICS SUB-COMMITTEE 19TH MEETING/2014).

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Written informed consent was obtained from all participants involved in this study.

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Parekh, P., Gozi, A., Reddi, V.S.K. et al. Resting state functional connectivity and structural abnormalities of the brain in acute retarded catatonia: an exploratory MRI study. Eur Arch Psychiatry Clin Neurosci 272, 1045–1059 (2022). https://doi.org/10.1007/s00406-021-01345-w

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