Identification of Neurophysiological Markers of Verbal Information Processing Using Cognitive Evoked Potentials for Studying Schizophrenia Spectrum Disorders

The aim of the study is to identify neurophysiological markers of information processing sensitive to verbal thinking impairment in persons with schizotypal personality organization using the method of cognitive evoked potentials.

Materials and Methods. Cognitive evoked potentials were studied in 40 students of higher school with high and low (control) scores obtained on the Schizotypal Personality Questionnaire (SPQ) in response to the presentation of visual verbal information in the form of agreed word-combinations. In the first series of presentations, it was necessary to refer the attribute to one of the categories and to read the noun silently (non-target condition). In the second series, the attribute should be read silently, and then the following noun has to be categorized (target condition). There has been performed a cluster analysis of the evoked potential curves obtained in response to the noun presentation in the target and non-target conditions in the groups of participants with high and low scores gained on SPQ.

Results. Processing of the verbal stimulus under passive reading conditions and under the conditions of word categorization within the frameworks of a simple context has shown that in the group with low scores on the schizotypal questionnaire, lateralization of the N150 component to the left side was observed in contrast to the group with high scores. In this group, increase of the N400 component amplitude was found in response to the words presented for their passive reading in comparison with the categorization condition. On the contrary, in the group with high schizotypy scores, the N400 component appeared to be insensitive to the type of the task, i.e. neurophysiological differences were not expressed between reading and performing stimuli categorization task. These persons were found to have the decreased amplitude of the late positive component as compared to the control group under the condition of passive reading of the words. Increase of the late negative wave amplitude was registered in response to the target words subjected to categorization in comparison with reading in both groups of participants. Insufficiency of language lateralization and deficit connected with the language networks being activated automatically at the initial stage of word recognition are observed in the examined persons with schizotypy. Additionally, processing of the information in these persons at the stage of lexical-semantic processes is weakly modulated by the task imposing different requirements on the level of mental activity control. Some reduction of mnestic process activation is also possible, which is manifested during passive reading of the words, but not in the conditions of their categorization.

Conclusion. The research conducted may serve as a starting point for a more detailed and long-term study of the fundamental mechanisms of impairment in information processing in the course of clinically evident pathology formation. In the applied aspect, the work may be considered as a contribution to the ongoing search for neurophysiological markers for early diagnosis of schizophrenia spectrum disorders.

1. Lenzenweger M.F. Schizotypy, schizotypic psycho­pathology and schizophrenia. World Psychiatry 2018; 17(1): 25–26, https://doi.org/10.1002/wps.20479.
2. Lenzenweger M.F. Schizotypy, schizotypic psycho­pathology, and schizophrenia: hearing echoes, leveraging prior advances, and probing new angles. Schizophr Bull 2018; 44(suppl_2): S564–S569, https://doi.org/10.1093/schbul/sby083.
3. Radanovic M., de Sousa R.T., Valiengo L., Gattaz W.F., Forlenza O.V. Formal thought disorder and language impairment in schizophrenia. Arq Neuropsiquiatr 2013; 71(1): 55–60, https://doi.org/10.1590/s0004-282x2012005000015.
4. Tonelli H.A. How semantic deficits in schizotypy help understand language and thought disorders in schizophrenia: a systematic and integrative review. Trends Psychiatry Psychother 2014; 36(2): 75–88, https://doi.org/10.1590/2237-6089-2013-0053.
5. Delogu F., Brouwer H., Crocker M.W. Event-related potentials index lexical retrieval (N400) and integration (P600) during language comprehension. Brain Cogn 2019; 135: 103569, https://doi.org/10.1016/j.bandc.2019.05.007.
6. Hagoort P., Hald L., Bastiaansen M., Petersson K.M. Integration of word meaning and world knowledge in language comprehension. Science 2004; 304(5669): 438–441, https://doi.org/10.1126/science.1095455.
7. Mar’ina I.V., Strelets V.B. Verbal stimuli semantics and relevance of ERPs. Zhurnal vysshei nervnoi deyatelnosti imeni I.P. Pavlova 2010; 60(1): 22–31.
8. Hokama H., Hiramatsu K., Wang J., O’Donnell B.F., Ogura C. N400 abnormalities in unmedicated patients with schizophrenia during a lexical decision task. Int J Psychophysiol 2003; 48(1): 1–10, https://doi.org/10.1016/s0167-8760(02)00156-3.
9. Kiang M., Kutas M., Light G.A., Braff D.L. An event-related brain potential study of direct and indirect semantic priming in schizophrenia. Am J Psychiatry 2008; 165(1): 74–81, https://doi.org/10.1176/appi.ajp.2007.07050763.
10. Lepock J.R., Mizrahi R., Korostil M., Maheandiran M., Gerritsen C.J., Drvaric L., Ahmed S., Bagby R.M., Kiang M. N400 event-related brain potential evidence for semantic priming deficits in persons at clinical high risk for psychosis. Schizophr Res 2019; 204: 434–436, https://doi.org/10.1016/j.schres.2018.08.033.
11. Kiang M., Kutas M. Association of schizotypy with semantic processing differences: an event-related brain potential study. Schizophr Res 2005; 77(2–3): 329–342, https://doi.org/10.1016/j.schres.2005.03.021.
12. Kiang M., Prugh J., Kutas M. An event-related brain potential study of schizotypal personality and associative semantic processing. Int J Psychophysiol 2010; 75(2): 119–126, https://doi.org/10.1016/j.ijpsycho.2009.10.005.
13. Del Goleto S., Kostova M., Blanchet A. Impaired context processing during irony comprehension in schizotypy: an ERPs study. Int J Psychophysiol 2016; 105: 17–25, https://doi.org/10.1016/j.ijpsycho.2016.04.009.
14. Mathalon D.H., Faustman W.O., Ford J.M. N400 and automatic semantic processing abnormalities in patients with schizophrenia. Arch Gen Psychiatry 2002; 59(7): 641–648, https://doi.org/10.1001/archpsyc.59.7.641.
15. Mathalon D.H., Roach B.J., Ford J.M. Automatic semantic priming abnormalities in schizophrenia. Int J Psychophysiol 2010; 75(2): 157–166, https://doi.org/10.1016/j.ijpsycho.2009.12.003.
16. Ryu V., An S.K., Ha R.Y., Kim J.A., Ha K., Cho H.S. Differential alteration of automatic semantic processing in treated patients affected by bipolar mania and schizophrenia: an N400 study. Prog Neuropsychopharmacol Biol Psychiatry 2012; 38(2): 194–200, https://doi.org/10.1016/j.pnpbp.2012.03.009.
17. Rugg M.D., Curran T. Event-related potentials and recognition memory. Trends Cogn Sci 2007; 11(6): 251–257, https://doi.org/10.1016/j.tics.2007.04.004.
18. Van Strien J.W., Hagenbeek R.E., Stam C.J., Rombouts S.A.R.B., Barkhof F. Changes in brain electrical activity during extended continuous word recognition. Neuroimage 2005; 26(3): 952–959, https://doi.org/10.1016/j.neuroimage.2005.03.003.
19. Bermúdez-Margaretto B., Beltrán D., Domínguez A., Cuetos F. Repeated exposure to “meaningless” pseudowords modulates LPC, but not N(FN)400. Brain Topogr 2015; 28(6): 838–851, https://doi.org/10.1007/s10548-014-0403-5.
20. Toth M., Sambeth A., Blokland A. EEG correlates of old/new discrimination performance involving abstract figures and non-words. Brain Sci 2021; 11(6): 719, https://doi.org/10.3390/brainsci11060719.
21. Kim M.S., Kwon J.S., Kang S.S., Youn T., Kang K.W. Impairment of recognition memory in schizophrenia: event-related potential study using a continuous recognition task. Psychiatry Clin Neurosci 2004; 58(5): 465–472, https://doi.org/10.1111/j.1440-1819.2004.01287.x.
22. Rebreikina A.B., Larionova E.V., Varlamov A.A. Event-related synchronization/desynhronization during processing of target, no target and unknown visually presented words. Zhurnal vysshei nervnoi deyatelnosti imeni I.P. Pavlova 2015; 65(1): 92–104, https://doi.org/10.7868/s004446771501013x.
23. Prodius P.A., Nuzhina N.S., Mukhina I.V. Lexical and regulative features of processing visual verbal information in simple context. Vestnik novyh medicinskih tehnologij 2017; 24(4): 157–162, https://doi.org/10.12737/article_5a38fc3a38f3f0.18058568.
24. Bender S., Behringer S., Freitag C.M., Resch F., Weisbrod M. Transmodal comparison of auditory, motor, and visual post-processing with and without intentional short-term memory maintenance. Clin Neurophysiol 2010; 121(12): 2044–2064, https://doi.org/10.1016/j.clinph.2010.05.008.
25. Bender S. P 17 neural signatures of post-perceptual attention and selective working memory encoding. Clin Neurophysiol 2017; 128(10): e334–e335, https://doi.org/10.1016/j.clinph.2017.06.096.
26. Niznikiewicz M.A., Shenton M.E., Voglmaier M., Nestor P.G., Dickey C.C., Frumin M., Seidman L.J., Allen C.G., McCarley R.W. Semantic dysfunction in women with schizotypal personality disorder. Am J Psychiatry 2002; 159(10): 1767–1774, https://doi.org/10.1176/appi.ajp.159.10.1767.
27. Wang K., Wang Y., Yan C., Wang Y.N., Cheung E.F.C., Chan R.C.K. Semantic processing impairment in individuals with schizotypal personality disorder features: a preliminary event-related potential study. Prog Neuropsychopharmacol Biol Psychiatry 2013; 40: 93–102, https://doi.org/10.1016/j.pnpbp.2012.08.019.
28. Treiman R. Linguistics and reading. In: Handbook of linguistics. 2nd edition. Aronoff M., Rees-Miller J. (editors). Wiley-Blackwell; 2017; p. 617–626.
29. Noesselt T., Shah N.J., Jäncke L. Top-down and bottom-up modulation of language related areas — an fMRI study. BMC Neurosci 2003; 4: 13, https://doi.org/10.1186/1471-2202-4-13.
30. Bemis D.K., Pylkkänen L. Simple composition: a magnetoencephalography investigation into the comprehension of minimal linguistic phrases. J Neurosci 2011; 31(8): 2801–2814, https://doi.org/10.1523/jneurosci.5003-10.2011.
31. Raine A. The SPQ: a scale for the assessment of schizotypal personality based on DSM-III-R criteria. Schizophr Bull 1991; 17(4): 555–564, https://doi.org/10.1093/schbul/17.4.555.
32. Lyashevskaya O.N., Sharov S.A. Chastotnyy slovar’ sovremennogo russkogo yazyka [Frequency dictionary of the modern Russian language]. Мoscow: Azbukovnik; 2009; 1087 p.
33. Maris E., Oostenveld R. Nonparametric statistical testing of EEG- and MEG-data. J Neurosci Methods 2007; 164(1): 177–190, https://doi.org/10.1016/j.jneumeth.2007.03.024.
34. Williams L.M., Gordon E., Wright J., Bahramali H. Late component ERPs are associated with three syndromes in schizophrenia. Int J Neurosci 2000; 105(1–4): 37–52, https://doi.org/10.3109/00207450009003264.
35. Bramon E., Rabe-Hesketh S., Sham P., Murray R.M., Frangou S. Meta-analysis of the P300 and P50 waveforms in schizophrenia. Schizophr Res 2004; 70(2–3): 315–329, https://doi.org/10.1016/j.schres.2004.01.004.
36. Rosburg T., Boutros N.N., Ford J.M. Reduced auditory evoked potential component N100 in schizophrenia — a critical review. Psychiatry Res 2008; 161(3): 259–274, https://doi.org/10.1016/j.psychres.2008.03.017.
37. Ferreira-Santos F., Silveira C., Almeida P.R., Palha A., Barbosa F., Marques-Teixeira J. The auditory P200 is both increased and reduced in schizophrenia? A meta-analytic dissociation of the effect for standard and target stimuli in the oddball task. Clin Neurophysiol 2012; 123(7): 1300–1308, https://doi.org/10.1016/j.clinph.2011.11.036.
38. Spironelli C., Angrilli A., Stegagno L. Failure of language lateralization in schizophrenia patients: an ERP study on early linguistic components. J Psychiatry Neurosci 2008; 33(3): 235–243.
39. Vercammen A., de Haan E.H.F., Aleman A. Hearing a voice in the noise: auditory hallucinations and speech perception. Psychol Med 2008; 38(8): 1177–1184, https://doi.org/10.1017/s0033291707002437.
40. Ilankovic L.M., Allen P.P., Engel R., Kambeitz J., Riedel M., Müller N., Hennig-Fast K. Attentional modulation of external speech attribution in patients with hallucinations and delusions. Neuropsychologia 2011; 49(5): 805–812, https://doi.org/10.1016/j.neuropsychologia.2011.01.016.
41. Aleman A., Böcker K.B.E., Hijman R., de Haan E.H.F., Kahn R.S. Cognitive basis of hallucinations in schizophrenia: role of top-down information processing. Schizophr Res 2003; 64(2–3): 175–185, https://doi.org/10.1016/s0920-9964(03)00060-4.
42. Mar’ina I.V., Strelets V.B, Garakh Zh.V., Novototskii-Vlasov V.Iu., Zaitseva Iu.S. Analysis of event-related potentials to verbal stimuli in healthy subjects and schizophrenia patients. Zhurnal vysshei nervnoi deyatelnosti imeni I.P. Pavlova 2012; 62(2): 157–164.
43. Kiang M. Schizotypy and language: a review. J Neurolinguistics 2010; 23(3): 193–203, https://doi.org/10.1016/j.jneuroling.2009.03.002.
44. Kutas M., Van Petten C., Besson M. Event-related potential asymmetries during the reading of sentences. Electroencephalogr Clin Neurophysiol 1988; 69(3): 218–233, https://doi.org/10.1016/0013-4694(88)90131-9.
45. Franklin M.S., Dien J., Neely J.H., Huber E., Waterson L.D. Semantic priming modulates the N400, N300, and N400RP. Clin Neurophysiol 2007; 118(5): 1053–1068, https://doi.org/10.1016/j.clinph.2007.01.012.
46. Lau E.F., Phillips C., Poeppel D. A cortical network for semantics: (de)constructing the N400. Nat Rev Neurosci 2008; 9(12): 920–933, https://doi.org/10.1038/nrn2532.
47. Leavitt V.M., Goldberg T.E. Episodic memory in schizophrenia. Neuropsychol Rev 2009; 19: 312–323, https://doi.org/10.1007/s11065-009-9107-0.
48. Toulopoulou T., Rabe-Hesketh S., King H., Murray R.M., Morris R.G. Episodic memory in schizophrenic patients and their relatives. Schizophr Res 2003; 63(3): 261–271, https://doi.org/10.1016/s0920-9964(02)00324-9.
49. Sahakyan L., Kwapil T.R. Moving beyond summary scores: decomposing free recall performance to understand episodic memory deficits in schizotypy. J Exp Psychol Gen 2018; 147(12): 1919–1930, https://doi.org/10.1037/xge0000401.
50. Hahne A., Friederici A.D. Electrophysiological evidence for two steps in syntactic analysis: early automatic and late controlled processes. J Cogn Neurosci 1999; 11(2): 194–205, https://doi.org/10.1162/089892999563328.
51. Contier F., Weymar M., Wartenburger I., Rabovsky M. Sustained attention as measured by reaction time variability is a strong modulator for the P600, but not the N400. J Cogn Neurosci 2022; 34(12): 2297–2310, https://doi.org/10.1162/jocn_a_01918.

Nuzhina N.S., Prodius P.A., Mukhina I.V. Identification of Neurophysiological Markers of Verbal Information Processing Using Cognitive Evoked Potentials for Studying Schizophrenia Spectrum Disorders. Sovremennye tehnologii v medicine 2022; 14(6): 53, https://doi.org/10.17691/stm2022.14.6.06