Delta Power in Sleep in Relation to Neuropsychological Performance in Healthy Subjects and Schizophrenia Patients

The original sample comprised 17 schizophrenia inpatients (seven women) diagnosed according to the International Classification of Diseases (subtypes: paranoid [N=15], hebephrenic [N=1], undifferentiated [N=1]) and 17 healthy subjects matched for age, sex and years of education according to the German school system. In one patient only two EEG channels were admitted, so he had to be excluded from spectral analysis. All patients were on a stable regimen of the antipsychotic amisulpride (median dose=600mg, range=100 to 800mg). Three patients received a concomitant sedative medication with zolpidem (10mg/day; two patients) or diazepam (7.5mg/day; one patient). Any participant with a relevant additional medical condition was excluded by medical history, physical examination, and routine laboratory investigation, including urinary drug screening. All participants gave their informed written consent. The study was approved by the local ethics committee and conforms to the Declaration of Helsinki, Finland.

Each subject spent two nights in our sleep laboratory. The first night was used for adaptation to the conditions in the sleep laboratory. Sleep was recorded between lights off (regulated by the subjects themselves between 10 p.m. and 12 p.m.) and lights on (at 6:45 a.m.). Prior to polysomnography of the second night and the next morning at 7:30 a.m., we performed neuropsychological tasks. Sleep was recorded employing standard procedures, and the following parameters were measured: Electroencephalographic activity (EEG: Fz, F3, F4, F7, F8, C3, C4, T3, T4, T5, T6, Pz, P3, P4, O1, O2 according to the 10–20 system), electrooculographic activity (EOG) and submental electromyographic activity (EMG). Recordings were visually scored according to standard criteria 11 by a trained rater under blind conditions. These results are described elsewhere. 7

For spectral analysis all EEG electrodes mentioned above were referenced against Fpz. The fast Fourier transform (FFT) algorithm was used, and the truncating error was reduced by applying a Hanning window. The EEG signals were A/D converted at 100 samples per second with a 12 bit resolution. Only artifact-free epochs of 30-second duration were analyzed. The log-transformed absolute power values of the delta range (0.5–4 Hz) of each sleep stage and of all channels were used for further analysis.

We used Trail Making Tests A and B for testing attention, cognitive flexibility and psychomotor speed in the evening and in the morning. 12 Declarative memory was assessed by the nonverbal Rey-Osterrieth Complex Figure Test (copy in the evening and announced recall in the morning). 13 For testing procedural learning we used a mirror-tracing skill. Subjects were to trace carefully inside the doubled lines of a triangle (for warming up, data not evaluated) and a star in the evening and in the morning. Direct visual access to the platform with the figures was prevented by a 30- by 22-cm board. The figures could only be seen via a 26- by 18-cm mirror. We assessed the overnight improvement (ratio of drawing time in the morning to drawing time in the evening). Aspects of spatial memory were measured by a test established by Smith and Milner. 14 Eleven toys are placed on a board. In the evening the only task is to guess on the retail price of each item. In the morning the task is to correctly replace all 11 items on the empty board. The distance between the assigned and original position of the objects is measured, and all numbers are added up. For measurement of executive function we performed the Tower of Hanoi (four disk version). To assess verbal intelligence, we used the Mehrfach-Wortschatz-Intelligenz-Test (Multiple Choice Word Fluency Test; MWT-B). 15

As the data do not constantly meet criteria for normal distribution, we used nonparametric statistics and provide median and range as descriptives. A Mann-Whitney test (two-tailed) was used to compare healthy subjects and patients. The relationship between sleep and neuropsychological parameters was examined by nonparametric correlations (Spearman-Rho, two-tailed). The level of significance was set at 5%. No adjustment of the error probabilities for multiple testing was performed because of the explorative nature of the study. Therefore, all results have been treated with particular caution and have been considered for their consistency with other results.

There were no significant differences between healthy subjects and schizophrenia patients regarding age (31 years [24 to 43 years] versus 31 years [22 to 44 years], respectively), premorbid verbal intelligence (107% [92% to 136%] versus 112% [97% to 143%], respectively) and education (13 years [9 to 13 years] versus 12 years [9 to 13 years], respectively; always median and range). The median of the Positive and Negative Syndrome Scale (PANSS) total score 16 was 77 (range=52 to 112). In almost all neuropsychological tasks patients performed significantly worse in the morning and in the evening; only mirror tracing revealed no significant differences between patients and comparison subjects. 7 Delta power in SWS was significantly reduced in schizophrenia patients in comparison to matched healthy subjects in temporal and occipital channels ( Table 1 ). There were no significant differences of delta power in Stage 2 sleep and REM sleep in patients versus comparison subjects.

There were no significant correlations between performance of any neuropsychological task and age, verbal intelligence, or education level. As shown in Table 2, all significant correlations in healthy subjects were seen in this way: the higher the delta power in sleep, the better the waking performance or overnight improvement in different neuropsychological tasks. A highly significant correlation was seen between recall of the Rey figure and delta power in SWS in a left frontal channel. A high number of significant correlations was found between neuropsychological tasks and delta power in SWS. There was a lower number regarding Stage 2 sleep and only few concerning REM sleep. Delta power in SWS or Stage 2 sleep was mainly significantly correlated with performance in tests carried out in the morning. Most of the significant correlations were found in frontal channels.

There were no significant correlations between age, total PANSS score or dosage of amisulpride and performance in any neuropsychological task in schizophrenia patients. Similar to the results of healthy subjects, patients with schizophrenia showed the highest number of significant correlations in neuropsychological performance with delta power in SWS. There were only few significant correlations of neuropsychological performance and delta power in Stage 2 sleep and REM sleep ( Table 3 ).

Because five of 16 patients with schizophrenia showed a duration of SWS of less than 4 minutes, only 11 patients (all with duration of SWS of longer than 18 minutes) were included in the correlation analyses of delta power in SWS compared with 11 healthy subjects matched for age, sex, and education level ( Table 4 ). For SWS in both groups significant positive correlations were found with TMT-A, in comparison subjects mainly with morning execution and in schizophrenia patients mainly with performance in the evening. Whereas a predominance of significant positive correlations between neuropsychological performance and delta power in frontal channels was seen in healthy subjects, this was not so in schizophrenia patients. In contrast to healthy subjects, schizophrenia patients’ better performance on the Tower of Hanoi puzzle correlated with a lower delta power in different sleep stages.