Deficits of entropy modulation of the EEG: A biomarker for altered function in schizophrenia and bipolar disorder?

Deficits of entropy modulation of the EEG: A biomarker for altered function in schizophrenia and bipolar disorder?

J Psychiatry Neurosci 2020;45(5):322-333 | PDF | Appendix

Vicente Molina, MD, PhD; Alba Lubeiro, PhD; Rodrigo de Luis Garcia, PhD; Javier Gomez-Pilar, PhD; Oscar Martín-Santiago, MD, PhD; María Iglesias-Tejedor, MD; Pedro Holgado-Madera, MD; Rafael Segarra-Echeverría, MD, PhD; María Recio-Barbero, MSc; Pablo Núñez, MSc; Mahmoud Karim Haidar, MD; Jessica Fernández-Sevillano, MSc; Javier Sanz-Fuentenebro, MD, PhD

Background: The synchronized activity of distributed neural assemblies — reflected in the electroencephalogram (EEG) — underpins mental function. In schizophrenia, modulation deficits of EEG spectral content during a P300 task have been replicated. The effects of treatment, chronicity and specificity in these deficits and their possible relationship with anatomic connectivity remain to be explored.

Methods: We assessed spectral entropy modulation of the EEG during a P300 task in 79 patients with schizophrenia (of those, 31 were in their first episode), 29 patients with bipolar disorder and 48 healthy controls. Spectral entropy values summarize EEG characteristics by quantifying the irregularity of spectral content. In a subsample, we calculated the network architecture of structural connectivity using diffusion tensor imaging and graph-theory parameters.

Results: We found significant spectral entropy modulation deficits with task performance in patients with chronic or first-episode schizophrenia and in patients with bipolar disorder, without significant pre-stimulus spectral entropy differences. The deficits were unrelated to treatment doses, and spectral entropy modulation did not differ between patients taking or not taking antipsychotics, lithium, benzodiazepines or antidepressants. Structural connectivity values were unrelated to spectral entropy modulation. In patients with schizophrenia, spectral entropy modulation was inversely related to negative symptoms and directly related to verbal memory.

Limitations: All patients were taking medication. Patients with bipolar disorder were euthymic and chronic. The cross-sectional nature of this study prevented a more thorough analysis of state versus trait criteria for spectral entropy changes.

Conclusion: Spectral entropy modulation with task performance is decreased in patients with schizophrenia and bipolar disorder. This deficit was not an effect of psychopharmacological treatment or structural connectivity and might reflect a deficit in the synchronization of the neural assemblies that underlie cognitive activity.

Submitted Feb. 14, 2019; Revised Sep. 30, 2019; Accepted Nov. 17, 2019; Published online Feb. 26, 2020

Acknowledgements: This work has been supported by the following grants: the “Instituto de Salud Carlos III” (PI15/00299 and PI18/00178) the” Gerencia Regional de Salud de Castilla y León” (GRS GRS 1485/A/17 and GRS 1721/A/18); the ‘Ministerio de Economía, Industria y Competitividad” and FEDER (TEC2014-53196-R), “Consejería de Educación de la Junta de Castilla y León” (VA059U13 and VA057P17); and predoctoral fellowship to A. Lubeiro (“Consejería de Educación Junta de Castilla y León”). J. Gomez-Pilar is supported by a predoctoral fellowship from the University of Valladolid. P. Holgado-Madera is supported by a predoctoral fellowship from the Consejería de Educación Junta de Castilla y León and European Social Fund. P. Núñez is supported by a predoctoral scholarship ‘Ayuda para contratos predoctorales para la Formación de Profesorado Universitario (FPU)’ from the ‘Ministerio de Educación, Cultura y Deporte’ (FPU17/00850). J. Fernández-Sevillano is supported by the Predoctoral Training Programme of the Education Department of the Basque Government.

Affiliations: From the Psychiatry Department, School of Medicine, University of Valladolid, Valladolid, Spain (Molina, Lubeiro); the Psychiatry Service, Clinical Hospital of Valladolid, Valladolid, Spain (Molina, Martín-Santiago); the Neurosciences Institute of Castilla y León (INCYL), University of Salamanca, Salamanca, Spain (Molina); the Imaging Processing Laboratory, University of Valladolid, Valladolid, Spain (de Luis Garcia); the Biomedical Engineering Group, University of Valladolid, Valladolid, Spain (Gomez-Pilar, Núñez); the Neurophysiology Service, Clinical Hospital of Valladolid, Valladolid, Spain (Iglesias-Tejedor); the Psychiatry Service, Doce de Octubre University Hospital, Madrid, Spain (Holgado-Madera, Sanz-Fuentenebro); the Psychiatry Service, Cruces Hospital, Bilbao, Spain (Segarra-Echeverría, Recio-Barbero); and the Psychiatry Service, Santiago Apostol Hospital, Vitoria, Spain (Haidar, Fernández-Sevillano).

Competing interests: None declared.

Contributors: V. Molina and R. de Luis Garcia designed the study. V. Molina, A. Lubeiro, O. Martín-Santiago, M. Iglesias-Tejedor, P. Holgado-Madera, R. Segarra-Echeverría, M. Recio-Barbero, P. Núñez, M. Haidar, J. Fernández-Sevillano and J. Sanz-Fuentenebro acquired the data, which V. Molina, R. de Luis Garcia, J. Gomez-Pilar and P. Núñez analyzed. V. Molina and A. Lubeiro wrote the article, which all authors reviewed. All authors approved the final version for publication and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

DOI: 10.1503/jpn.190032

Correspondence to: V. Molina, Department of Psychiatry, School of Medicine, University of Valladolid. Av. Ramón y Cajal, 7, Valladolid 48005, Spain;