ИСТИНА

Saccadic eye-movements present an informative model for the study of adaptive behavior cognitive control. Attention, decision-making and inhibition processes at different stages of saccade programming can be evaluated by the analysis of ERP components (Slavutskaya et al., 2008). The saccadic eye-movement dysfunctions were repeatedly found in sсhizophrenia however the data on the prodromal stage of the disease are rather inconsistent. The aim of the study was to identify EEG markers associated with different subcomponents of cognitive control processes and to analyze their impairment in patients at ultra-high risk (UHR) of schizophrenia. In 20 mentally healthy subjects and 20 UHR patients (right - handed men, 18-20 years old) P1, N1, P2, N2 and P3 ERP components in "Go / No go" saccadic paradigm have been studied. “Go” and “No go” visual stimuli were presented on darkened display as white circles or crosses (correspondingly or vice versa in 50% of subjects) at 7 degrees distance to the left or right from the central fixation point. Eye movements were recorded using EOG. 25 channels EEGs were recorded also. In Go condition the method of selective EEG averaging was applied. EEG fragments in the range of saccade mean latency ± 20-30 ms were averaged. In “No go” condition the same number of randomly chosen fragments was averaged. Error saccades to inhibitory stimuli were higher in patients as compared to healthy subjects (46 ± 7% and 24 ± 4%, respectively, p <0.001), which may be due to violation of attention and voluntary inhibition control functions at the prodromal stage of schizophrenia. The Go-P1 amplitude was 1.9 ± 0.4 μV higher (p <0.001) in UHR patients group Also, No go P1 amplitude was 1.4 ± 0.3 μV lower than Go-P1 one (p <0.005). The findings may reflect a compensatory increase of the cortical activation to “Go” stimuli in condition of “hypofrontality” and suppression of attention to inhibitory stimuli. In patients, N1 amplitudes both to Go and No go stimuli were decreased for rightward stimuli only (by 1.3 ± 0.3 μV, p <0.05), that may be due to a violation of right-directed attention processes which are attributed to the left hemisphere dysfunction as was reported earlier in schizophrenia (Sharma et al., 2013). So, sensory processing mechanisms in the right hemisphere seems partially intact at the prodromal stage of schizophrenia. At the same time, N1 peak latency was 17.8 ± 7ms lower in UHR patients as compared to healthy subjects (p <0.05) regardless of the stimulus signal value and saccade direction. It was in line with a decrease of saccade latencies in the former group (209 ± 76 ms vs 251 ± 72 ms, p <0.001, respectively). The findings may indicate the sensory processing shortening as a factor that attenuates the effectiveness of cognitive control (Strelets et al., 2012). P2 and N2 were analyzed only in the “No go” conditions, since they were often distorted by artifacts from eye movements and motor potentials in “Go” condition. There were no intergroup differences by No go-P2. No go-P2 in some paradigms is considered as a marker of decision making (Schuermann B. et al. 2012). Therefore, corresponding processes in UHR patients seems partly intact. N2 peak latency was higher or similar to saccade latency, which allows us to consider it as a marker of response monitoring and memory updating – the processes usually attributed to P3 range. Half of both groups showed No Go-N2 peak location in medial areas (Fz, FCz, Cz, CPz, or Pz) that are presumably involved in frontal- and parietal-medial-thalamic selective attention networks (Schlag- Rey, Schlag, 1992). This fact may suggests that No Go-N2 component reflects the attention influence at the final stage of the inhibitory response. There were no intergroup differences by No Go-N2 and No Go-P3 amplitudes, which allows for similarity of neuronal circuits activity magnitude during the final stage of inhibitory response. On the other hand, No go-N2 and No Go- P3 latencies were increased in UHR group. However, the significant differences by No go-N2 latency occurred only for the left inhibitory stimuli projected to the right hemisphere. This fact may emphasize partial “normality” of corresponding left hemisphere circuits at the stage of saccade inhibition monitoring in UHR patients. Intergroup differences by peak topography and spatiotemporal dynamics of ERP components may be associated with the diversity of spatial organization of cognitive control networks in norm and UHR. In patients, ERP subcomponents peaks were located mainly in fronto-central areas. The latter presumably reflects the compensation of “frontal deficiency” accompanying by attenuation of prefrontal top-down effects in prodrome of schizophrenia. Therefore, ERPs in the “Go\No go” paradigm point to violation of sensory perception, spatial attention, and result monitoring in UHR patients. The findings suggest a complicated trajectory of cognitive impairment development at the pre-manifest stage of schizophrenia. Neuronal circuits of right hemisphere are seemingly functioning almost as in norm at the stage of sensory processing. The same can be assumed for the left hemisphere circuits at the stage of result monitoring and memory updating.