In patients suffering from schizophrenia, polysomnographic findings are less consistent than in depression. Some authors noted SWS reduction 114; however, this was not confirmed by other investigators 115, 116. Lauer and associates 117 did not find any significant differences in sleep structure between a paranoid group of schizophrenic patients and a healthy control group, while, according to Mendelson and co-workers 118, REM sleep percentage increases exactly before the exacerbation of psychotic symptoms and tremendously decreases during the exacerbation.
In some studies REM sleep latency was reduced 115,119-121, while in other studies it was normal 122-124. Some authors 121 suggested that symptoms of depression may be related to the decrease of REM sleep latency in schizophrenia; however, in other investigations 114, 125, REM latency was not related to depressive symptoms.
The difference between schizophrenia with the predomination of positive and negative symptoms in numerous clinical and physiological variables allows a prediction that this difference may also influence sleep architecture. Some sleep investigations have been performed using this paradigm directly or indirectly 115,120,122,126. These investigations concentrated mostly on the relationships between positive versus negative symptoms, SWS and REM sleep latency.
We investigated 34 patients with chronic schizophrenia on stable doses of neuroleptic medication10,127. They were divided into two groups according to the positive and negative syndrome score (PANSS) rating128. Group I contained seven men and two women (mean age 40 years) with positive/negative ratio > 1. Group II contained eight men and two women (mean age 41 years) with positive/negative ratio < 0.5. Thus, positive symptoms dominated in group I (28.1 vs. 11.8 in group II) and negative symptoms dominated in group II (30.8 vs. 20.0). The neuroleptic treatment was approximately similar in both groups. Sleep data were collected on two consecutive nights. There were no significant differences between both groups according to most sleep variables except for REM sleep percentage and EM density in REM sleep. In group I the mean REM sleep percentage was significantly lower (20%) than in group II (25%). REM sleep in the first cycle displayed a tendency to be higher in group II, but REM sleep latency was similar in both groups.
We also compared positive and negative symptoms in 11 patients with more than 25% REM sleep (group A) and in 14 patients with less than 20% REM sleep (group B). The mean level of positive symptoms was 15 m group A, and 20 in group B, while the mean level of negative symptoms was 27 and 25, respectively. Negative symptoms were relatively more predominant in group A with the increased REM sleep percentage. REM sleep latency demonstrated a non-significant tendency to be shorter in the group with an increased REM sleep percentage; however, it was in the normal range.
According to these data the ratio between positive and negative symptoms is not the only factor determining the representation of REM sleep. In group I this ratio was > 1; however, the mean REM sleep percentage was 20, while in group B, where REM sleep was less than 20, this ratio was less (0.8). On the other hand, in group II positive/ negative ratio was 0.38 and REM sleep percentage was 25%, while in group A, where REM percentage was more than 25%, this ratio was 0.55. In control healthy subjects matched to patients with schizophrenia according to age, the mean REM sleep percentage was 19%, very similar to patients in group I. These results suggest that a strong predominance of negative symptoms is associated with a relative increase of REM sleep percentage. However, the predominance of positive symptoms is not associated with REM sleep suppression less than the normal level and there is no linear relationship between REM sleep variables and the positive/ negative symptom ratio.
Also, we have estimated the relationship between EM density (averaged EM frequency in 1 min of REM sleep) and positive versus negative symptoms. In subgroups with a high (> 6) and low (< 2.5) mean EM density the level of negative symptoms was almost equal (31 and 33), but the level of positive symptoms was significantly higher in the subgroup with low EM (25.2 vs. 12.6). This finding was confirmed in further analysis of the data. In patients with a low score of positive symptoms, mean EM density was significantly higher than in patients with high scores 127. At the same time in patients with high and low scores of the negative symptoms EM density was similar. In patients with positive/negative symptom ratio < 0.4, EM density achieved maximum values in the first cycle. In other cycles, it was lower and almost equal, thus resembling EM distribution in depressed patients129. A significant negative correlation was found between the score of the positive symptoms and EM density in the first and third cycles, -0.45 and -0.50, respectively. These findings are in agreement with Neylan and colleagues 125, who reported an increased severity of psychosis after neuroleptic withdrawal simultaneously with the decrease in EM density. Our results correspond also with those of Tandon and associates 115, who reported that schizophrenic patients who were drug free only for 2-4 weeks (when the effect of neuroleptics is still present) displayed higher EM density in comparison with schizophrenic patients who were drug free for a longer time or drug naive. Tandon and co-workers 115 did not present data on positive symptoms after drug withdrawal. It is, however, not rare that the withdrawal of neuroleptics causes the exacerbation of psychotic (positive) symptoms 125.
Although the relationships between clinical symptoms and both REM sleep variables (REM sleep percentage and EM density) are in the same direction, it is worth mentioning the difference. The increase of REM sleep percentage is determined mainly by the predominance of negative symptoms, while the decrease of EM density is related to the level of positive symptoms. However, this is at least one possible interpretation of both relationships in the frame of the search activity concept. I suggest that the increased REM sleep percentage in group II is caused by the absence of search activity in patients with predominantly negative symptoms. Negative symptoms (apathy, flattened affect, low social activity, inattentiveness, lack of spontaneity in behavior and in mental activity, poverty of speech), like depression, display a lack of search activity that requires REM sleep for its compensation. However, in contrast to depression, negative schizophrenia is not accompanied by the regular decrease of REM sleep latency. It may depend on the different context of the renunciation of search in depression and negative schizophrenia. While in depression, and especially in anxious and agitated depression, renunciation of search is usually combined with increased affective tension, in negative schizophrenia it is usually accompanied by flattened affect. At the same time, any form of schizophrenia may be combined with depressive symptoms, and this can be an additional factor determining the lack of linear relationships between positive/negative symptom ratio and REM sleep.
There is another possible interpretation of the normal REM sleep latency in our patients. It has been shown 121,125 that REM latency correlates with SWS time. The exacerbation of psychosis following acute neuroleptic withdrawal may determine the suppression of SWS and as a result the decrease of REM latency 125. At the same time, the relapse of psychosis after neuroleptic withdrawal decreases the total REM time. Thus, the relapse of psychosis may cause a paradoxical combination of decreased REM sleep latency, decreased REM time and decreased phasic REM activity, while stable neuroleptic treatment, like in our investigation, causes a combination of increased REM duration and REM activity with normal REM sleep latency. However, the relationships between positive/ negative symptoms and sleep structure may be even more complicated and contradictory. Not only may the exacerbation of positive symptoms suppress SWS, Ganguli and associates 122 showed also that SWS and negative symptoms were negatively correlated, which may influence REM latency, especially in non-medicated schizophrenic patients. Positive symptoms represent very particular, misdirected and maladaptive, but at the same time very intense, search activity 20. Paranoid ideation and hallucinations correspond to the definition of search activity: active overt or covert behavior without definite forecast. Auditory hallucinations are associated with increased metabolic activity in brain centers for inner speech, i.e. that represent active verbalization. A schizophrenic patient cannot be sure about future 'events' in the artificial world he is building for himself, or about outcomes of his interactions with this world. At the same time, the person remains sensitive to all events and outcomes related to this artificial world. The hyperactivity of the brain catecholamine system in positive symptom schizophrenia also corresponds to the notion of search activity 20.
In healthy subjects, EMs in REM correlate with the active participation of the dreamer in dream scenarios and with dream content 35,75. Active events in dreams represent search activity that has to compensate the renunciation of search in the previous wakefulness 5. If search activity during wakefulness is already high, there is no need for high EM density in REM sleep. From my point of view, this may explain how neuroleptic withdrawal precipitated a psychotic relapse associated with the decline in REM sleep duration and EM activity 125, and explains why positive symptoms correlated negatively with EM density in our investigation.
The peculiarity of the FNE in schizophrenia also can be explained in the frame of the search activity concept. Neylan and associates 125 did not find FNE in schizophrenic patients on and off haloperidol therapy. In our investigations 10, 127, FNE according to our criteria (see above) was present only in 35% of schizophrenic patients, less than in MD. Interestingly, the age of patients who demonstrated FNE was significantly higher than the mean age of patients without FNE. Positive symptoms were higher in patients with FNE while negative symptoms were almost equal in both groups. When the ratio of positive/ negative symptoms was > 0.6, FNE was present in 71% of all cases, whereas when this ratio was < 0.4, FNE was present only in 17%. It was difficult to discriminate the influence of age and positive symptoms on the difference between REM sleep latency on the first and the second nights. The ratio of the first REM period to the total amount of REM sleep was not increased in the first night of schizophrenic patients, and in patients with FNE this variable was less than on the second night. In patients with a FNE, sleep efficiency on the first night was lower and the number of awakenings higher than on the first night in the control group of healthy subjects who demonstrated a FNE. Thus, it is possible to suggest that there is an exaggerated FNE in schizophrenic patients with relatively high positive symptoms in comparison to normal subjects.
Although patients with FNE were, in general, older than patients without FNE, it is very unlikely that FNE is directly determined by age. In the investigation of Ganguli and co-workers 122 almost half of the patients suffering from schizophrenia demonstrated FNE although all patients were young. In normal young subjects, FNE is a typical finding 45, 130. There are some reasons to suggest that positive symptoms play a key role in the FNE:
(1) Schizophrenic patients with positive symptoms, like PTSD patients, display an exaggerated orienting reaction 131. At the same time, patients whose negative symptoms predominate demonstrate a failure to respond to the environment 132.
(2) Schizophrenic patients with positive symptoms display higher reactivity to sensory and affective stimuli in comparison to patients with negative symptoms 135. Such sensitivity may increase with age.
(3) A relatively higher response of the brain monoamine system in patients with positive symptoms, in comparison to patients with negative symptoms 134, may also explain the appearance of the FNE as an exaggerated reaction in a new environment.
(4) As we have already shown, positive symptoms decrease REM sleep pressure. As a result, REM sleep pressure does not prevent FNE (the reverse of the situation in depressed patients with high REM sleep pressure and a low REM sleep flexibility).
It is interesting to discuss the difference between schizophrenic patients with positive symptoms and the above-mentioned patients with psychotic depression. The latter do not display FNE. It is possible to speculate that hallucinations and delusions of schizophrenic patients cause an active and outside oriented, although inappropriate and misdirected, search behavior while delusions in depressed patients are often mood-congruent and are related to the feeling of guilt, worthlessness, failure, to ruminative self-blaming and self-annihilation. Such delusions provide a basis for renunciation of search. It was shown 135 that psychotic depressive patients, in comparison to melancholic patients and to those with major depression without psychotic features, were significantly more likely to demonstrate marked psychomotor disturbances, to report feeling sinful and guilty, and to suffer from constipation, terminal insomnia, appetite loss and loss of interest and pleasure.
Our approach to the difference between psychotic mood-congruent depression and schizophrenia is in line with data 136 that cortisol non-suppression on the dexamethasone suppression test is most prominent in depression with mood-congruent delusions, in comparison to both non-psychotic depression and depression with mood-incongruent delusions. Lower rates of non-suppression were also observed in schizophrenia 137.
These data suggest that psychotic features in depression and schizophrenia may have different significance, and this proposition is confirmed by our data derived from sleep investigations.
Our group has shown that melatonin treatment of chronic schizophrenia definitely restored FNE in these patients in comparison to placebo treatment 138. There are different possibilities to explain these data. It is possible that melatonin enhances the alertness of schizophrenic patients in the unfamiliar situation as an outcome of the improved sleep quality on melatonin treatment during the previous nights 138. The restoration of FNE may result from the modulation of dopaminergic activity by melatonin in the neuroleptic-treated patients with schizophrenia.
Finally, we have investigated the relationship between objective sleep variables and subjective sleep estimation in schizophrenia 139. There are no systematic investigations of this topic. Patients with chronic schizophrenia demonstrated a high, and unexpected, ability to estimate correctly the duration of sleep latency. The correlation between objective and subjective sleep latency in patients was higher than in healthy subjects and in depressed patients. In healthy subjects and patients with mood disorders the duration of wakefulness before sleep onset is probably overestimated, owing to emotional tension caused by sleep delay. This emotional tension may interfere with the ability to estimate sleep latency. In chronic schizophrenic patients with a relative predominance of negative symptoms and with blunted affect, alteration of sleep onset does not cause any emotional reaction and its subjective estimation is not distorted.
At the same time, the subjective estimation of the duration of wakefulness in sleep correlated in schizophrenic patients with EM density in REM sleep. The same correlation was found in patients with MD (see above). As stressed previously, in healthy subjects EM density correlates with some features of dream reports. However, in schizophrenic patients we found a negative correlation between EM density and dream reports. It is possible to speculate that schizophrenic patients, as well p as patients with MD, perceive mental activity in REM sleep as wakefulness, and it is an important sign of the REM sleep functional insufficiency. According to the search activity concept, such functional insufficiency of REM sleep may play an important role in the pathogenesis of different mental disorders.
ADAPTIVE VS. MALADAPTIVE EMOTIONAL TENSION (ANXIETY) AND SLEEP
It is well known that anxiety is one of the main reasons for sleep disturbances. Anxiety causes prolonged sleep latency, decreased total sleep time, reduced SWS and reduced sleep efficiency partly due to the increased number of awakenings. Beyond the alterations of the objective sleep structure, anxiety may cause a negative subjective estimation of sleep 140. Sleep latency may be overestimated; awakenings filled with anxious feelings might be more easily fixed in memory than those without and will result in reports of poor sleep. Moreover, awakenings in NREM sleep, especially in the first sleep cycles, may cause the underestimation of the depth and duration of the preceding part of sleep 84.
The alterations of REM sleep variables in anxiety are less definite than alterations of non-REM sleep or of sleep duration. This may relate to the problem of the definition of anxiety.
Emotional tension (anxiety) is not a united psychophysiological state. It can be either maladaptive or adaptive in both nature and outcome. Adaptive emotional tension helps the subject to solve problems and to overcome obstacles, and has no negative outcome on health. Despite the theoretical and practical importance of the distinction between adaptive and maladaptive emotional tension, neither adequate theoretical approaches nor valid methods appear to distinguish between the two in past research. According to general activation theory, an optimal level of emotional tension is adaptive in helping the individual to solve problems and to overcome obstacles without any negative outcome for the organism. The Yerkes-Dodson law postulate that when the level of tension is extremely low or high, its outcome is regarded as negative with respect to performance, adaptation and health 141,142. However, there are many exceptions to the Yerkes-Dodson law. First, pathological emotional tension (neurotic anxiety) is always harmful, with respect not only to health but also to performance, thereby decreasing the effectiveness of the latter in a linear manner 143,144. Second, even a very high level of emotional tension can promote the activity of the subject (Figure 3.1).
According to Dienstbier 145, naturally evoked peripheral catecholamines never seem to be too high for optimal performance. In addition, when methods of coping were available, even very high arousal levels failed to elicit discomfort and negative emotions 146.
I suggest that the difference between productive emotional tension (the normal anxiety of a healthy individual in a state of stress), instrumental in mobilizing all psychological and physical resources to overcome obstacles, and unproductive emotional tension that hampers successful activity is determined by the presence or absence of search activity in the structure of emotional tension. Until search activity is present, anxiety is adaptive. All forms of maladaptive anxiety (like panic and neurotic anxiety) do not correspond to search activity, both according to the theoretical notion and clinical observations. During panic the results of the activity are not considered at any stage and cannot be used for the correction of behavior. Panic behavior during catastrophic events is usually displaced by or combined with depression 147,148. Panic may represent an exaggeration of normal anxiety that corresponds to the final point of the curvilinear line displaying relationships between emotional tension and adaptation or performance (see Figure 3.1). In this final point the emotional tension is very high while performance and adaptation are low. This happens, in particular, when vital motivations are increased and fear of the consequences of failure predominates over constructive attempts to find a reasonable solution to the problem; such fear does not allow the subject to follow up, to the end, any way of search and to use the current outcome of his/her own activity in order to correct this way. Finally, such fear deteriorates behavior. In panic, like in other states of emotional tension without search activity, the expenditure of brain monoamines exceeds their synthesis, and eventually there comes a pronounced drop in their levels and a secondary depression.
Neurotic anxiety, according to the psychodynamic concept, is a consequence of the repression of an unacceptable motive from consciousness. The repression can be regarded as a purely human variant of renunciation of search, of the modes of realization, of the unacceptable motive in overt behavior, and modes of integration of it with other realized behavioral orientations. Thus, repression simply represents a state of giving up in front of the inner motivational conflict and its outcome is, speaking metaphorically, a mental "freezing". It is the reason why neurotic anxiety caused by repression is maladaptive 85 and does not follow the Yerkes-Dodson law.
Benzodiazepines have different outcomes for adaptive and maladaptive emotional tension. It is well known that benzodiazepines sometimes enhance and sometimes diminish the behavior (motor) response to threatening signals 149. In moderate doses, they do not block active avoidance or even increase it, but they usually block freezing as a sign of renunciation of search 150. Maladaptive anxiety is more sensitive to anxiolytics, and because of the competition between renunciation of search and search behavior, freezing can be replaced by active avoidance.
However, benzodiazepines also block adaptive anxiety containing search activity, by increasing the sensory threshold for any meaningful information that can cause frustration. Imagine, for instance, a lecturer who is worrying about the possible outcome of his lecture. Even if it is a mobilizing and adaptive emotional tension, subjectively it is accepted as an unpleasant anxiety and has a negative connotation for the person: he prefers not to worry. If in order to cope with this anxiety he uses benzodiazepines, the adaptive mobilization is reduced and the lecture will be less successful.
Ledoux and Gorman 151 have recently confirmed our approach to anxiety. They stressed that a shift from passive suffering to active coping is the best way to treat anxiety caused by recent social events.
The search activity concept helps to solve some contradictions related to the dynamic of autonomic patterns in different forms of anxiety. Thus, there is a marked difference between the habituation of orienting reactions in healthy subjects versus subjects with psychopathology. In healthy subjects, the amplitude of the electrodermal reaction (EDR) during the first two orienting reactions is higher and the habituation is faster, while the spontaneous electrodermal activity is lower 152. If the spontaneous electrodermal activity reflects an inner emotional tension not relevant to the external task, and the evoked EDR reflects the emotional tension during decision making 153, it can be suggested that pathological subjects are overwhelmed by their emotional tension, which causes hyperarousal. This high arousal, however, reflects maladaptive emotional tension, is in competition with search activity and blocks normal forms of behavior requiring search activity, in particular, the orienting reaction. From my point of view, this is a more reasonable explanation than the explanation according to the 'law of initial level' 154. Wilder proposed that the higher the initial level of activity of the physiological system, the lower the reaction of the system on the relevant task. However, in healthy subjects involved in a meaningful activity and highly motivated, autonomic variables may increase regardless of their initial level 155,156. Wilder's law seems to be relevant only for pathological anxiety. Thus, the low autonomic reaction in pathologically anxious persons may not relate to the high initial level by itself, but rather to the inability of the subject to accept the challenge of the task that requires search activity.
Sleep structure is also able to separate adaptive and maladaptive anxiety. We analyzed sleep change in 27 healthy students on a post-examination night in comparison to post-holiday nights 2. Thirty minutes before the examination and 30 min after, we recorded their heart rate frequency, arterial blood pressure and bioelectrical activity of the orbicular muscles of the mouth. The latter, as other autonomic variables, is very sensitive to emotional tension. The control data on these indices were obtained on one of the term days. Before the examination all subjects showed an increase in autonomic variables and muscle tension compared with the control measures. However, after the examination, two groups could be separated. The group I subjects' (16 students) indices dropped to the control level, whereas the indices of subjects in group II remained at a stable high level. Students of group II demonstrated a significant increase in REM sleep percentage on the post-examination night compared with the control night and with the post-examination night of the group I subjects. On the post-examination night, the subjects of group II showed a positive correlation between the total duration of sleep and the proportion of REM sleep (0.74) and a negative correlation (- 0.6) between the duration of REM sleep and that of delta sleep. The subjects of group II showed worse results in resolving logical tasks on the evening after the examination (before sleep) than on the following morning; also, their results were worse than those of group I. They were working relatively faster but they made significantly more mistakes - thus they behaved in a more impulsive way. It is important to note that subjects in both groups did not differ according to the objective outcome of the stressful situation -all students passed the examination. Thus, stable emotional tension was not caused by the negative outcome of the examination.
We have proposed a hypothesis that the subjects of group I exhibited normal emotional tension, which ensured psychophysiological mobilization for overcoming the stressful situation and diminished when the situation passed. The subjects of group II displayed maladaptive emotional tension. It did not diminish after the stressful situation was over and required REM sleep for its disappearance. Additional support for this approach comes from data demonstrating that slow post-stress catecholamine decline is accompanied by poor performance, neuroti-cism and pathological anxiety 157.
Almost everybody who has ever passed examinations is familiar with such maladaptive tension. It prevents concentration on the particular text the subject is studying because the subject is overwhelmed with fears according to the predicted negative outcome of examinations. Instead of reading the text the subject is continually counting the number of pages he has yet to go. It is possible to suggest that coming examinations, as every stressful condition, provoke in such subjects deep and old neurotic complexes and feelings of inferiority, and this is the reason why the anxiety does not disappear even after the actual stressful situation is over. In order to cope with these activated complexes and feelings that provoke renunciation of search the subject has to go through REM sleep. Maladaptive anxiety determines paradoxical relationships between sleep disturbances and daytime alertness. Recently, we investigated daytime wakefulness/sleepiness and night sleep structure in patients with sleep apnea and in patients with depression/anxiety 158. We found that in patients with sleep apnea the ability to remain awake during soporific circumstances measured by the maintenance of wakefulness test (MWT) correlated negatively with stage 1 sleep. The latter correlated negatively with the total sleep time and with SWS. It looks very natural - the more disturbed the night's sleep due to sleep apnea, the more difficult it is to maintain daytime alertness. However, in patients with depression/anxiety, MWT scores correlated negatively with total sleep time and SWS (stage 3), while the multiple sleep latency test correlated negatively with total sleep time and sleep efficiency. This means that the more disturbed the night's sleep, the less easily is the subject able to go to sleep during the day. Maladaptive tension disturbs nighttime sleep and at the same time prevents daytime sleep. It determines a very well known paradoxical combination of subjective sleepiness (caused by nighttime sleep disturbance) with high irritation and inability to sleep.
ROLE OF SLEEP IN MEMORY FUNCTION: REM SLEEP, BEHAVIOR AND MEMORY
The outlined ideas concerning the function of REM sleep and dreams presented in part of this chapter can help to solve many debatable problems of sleep psychophysiology. Among such problems, in particular, is the role of sleep in memory and learning. Jenkins and Dallenbach 159 in their classical investigation demonstrated that recall was diminished less by a night of sleep than by an equivalent amount of wake time. However, in their theory no active role in memory consolidation and storage was ascribed to sleep; it was considered only as a period free from sensory interference.
The discovery of REM sleep and different NREM sleep stages elicited many modern investigations on the active role of these sleep stages in memory. The recent review by Stickgold 160 summarized data of investigations performed on animals and humans. It was shown that in animals, REM sleep increases after training on very different but complex tasks such as the multiple-goal maze, shuttle avoidance, classical conditioning and operant bar press, mostly after the so-called unprepared learning according to Seligman 161. This REM sleep increase appeared in special time periods (REM sleep 'windows' 162), often just before the critical level of success in the learning process was achieved 163 and correlated with the successful learning of new material. REM sleep deprivation performed after the learning process in such critical periods ('windows') disturbs retention. At the same time, performance of simple tasks was not impaired by REM sleep deprivation 164.
Investigations performed on humans have also shown that the relationship between the learning process and sleep depends on the task peculiarity. Tasks related to declarative memory (word recognition, retention of the word list or paired associates) are REM sleep independent and REM deprivation produced no effect on these tasks 165, while tasks related to procedural memory that require the development of new and flexible perceptual or motor skills - like mirror writing, the word fragment completion task or the Tower of Hanoi task 166 - are REM dependent 160. Declarative memory as opposed to procedural memory depends on SWS 167-169.
According to the above-mentioned data, many authors 160,162,164,170,171 suggest that REM sleep per se plays an important role in the consolidation of unusual and emotionally significant information, but not in the retention of ordinary information. However, it was shown that the creative (unusual) task, in most cases, is not solved in REM sleep per se, although after a dream with an active position of the dreaming subject the creative task in subsequent wakeful-ness is solved more successfully 172. On the other hand, REM sleep deprivation does not influence the learning process, if the learning prior to the deprivation was performed with intensity and success, and the task was realized during wakefulness 170. This means that REM sleep is not obligatory for the retention of information even if the task by itself is complex. There are some additional arguments against the idea of the direct participation of REM sleep in consolidation mechanisms:
(1) During the active search behavior in the stressful situation, consolidation of the new experience is essential for survival, but under these conditions REM sleep does not increase, and even decreases.
(2) The REM sleep percentage increase under neuroleptic treatment 118 has no beneficial effect on memory.
(3) Activating drugs, like amphetamine, have a tendency to suppress REM sleep but, at least, do not disturb memory 173.
(4) Despite marked suppression of REM sleep, antidepressants on the whole do not disrupt learning/memory 174.
As already mentioned, REM sleep becomes longer at certain stages during the solution of emotionally significant complex problems, which the animal or human subject is originally unprepared to handle 170. There is evidence suggesting that the greatest increase of REM sleep occurs during the 24 h before the critical level of success in the learning process 175,176. REM sleep deprivation carried out directly in this period impedes it. It is possible to suggest that REM sleep is particularly important for the animal during the critical period of an acute conversion from the previous stereotypical behavior to the new and flexible style of behavior.
It might be a sign that REM sleep plays only an indirect role in the process of retention by carrying out its main function - compensation of renunciation of search and restoration of search activity 4. A complex problem that the subject is not ready to solve, a difficult task that requires unprepared learning, may cause renunciation of search with much greater probability than a simple one, especially at the early stages of the solution when failures prevail over successes. In experiments on animals "the learning situation imposed is undoubtedly the most important and traumatic event in the life of the organism" 171, and such an event has a significant chance of producing a giving-up reaction (renunciation of search). Actually, the non- learning rats (rats that remain below the learning criteria) displayed a considerable majority of freezing responses daring training and thereby received the highest number of electric shocks 177. If search activity in REM sleep is unavailable (due to REM deprivation) and, consequently, does not overcome the state of renunciation of search, the latter itself will make it impossible to find the right solution or keep it in memory. REM deprivation after training leaves memory in a labile form and delays the process of consolidation 178, presumably due to the predominance of the maladaptive state of renunciation. Therefore, the lengthening of REM sleep exactly before the critical point in the learning, after which the animal fully develops the habit, is not surprising.
However, in some cases the lengthening of REM sleep may be insufficient to compensate for the very prominent state of renunciation of search. In such cases, REM sleep may increase precisely in those animals that are the least successful in forming the new habit 179, resembling the increase of REM sleep in depression. It is possible to suggest that in non-learning rats the compensatory REM sleep system is usually weak and functionally insufficient. This hypothesis corresponds to data 177 that the average duration of REM sleep episodes of baseline sleep of non-learning rats is significantly shorter in comparison to learning rats. These episodes may be less stable. In such cases stressful conditions of training may cause a relative increase of REM sleep that is nevertheless insufficient for compensation.
The peculiarity of neuronal activity in different functional states also does not confirm the theory of REM sleep's direct participation in memory consolidation. According to the dynamic of neuronal activity, in quiet rest and in SWS, information flows from hippocampus to neocortex, while in REM sleep and during active exploration in wakefulness 160,180, information flows in the opposite direction - from neocortex to hippocampus. Thus according to this variable, as well as according to die hippocampal theta-rhythm, active exploration in wakefulness and REM sleep are very similar to each other and opposite to SWS.
This confirms our conclusion about active exploration (search activity) in functionally sufficient REM sleep. However, it shows also that it is not necessary to ascribe memory consolidation by itself to REM sleep. The above-mentioned explanation of the indirect contribution of REM sleep in memory function is here more relevant. Renunciation of search makes any functions in wakefulness and sleep, including memory, less efficient, and if REM sleep overcomes renunciation of search and restores search activity it has also a positive outcome on memory. Furthermore, this approach provides an explanation for data being difficult to explain by the concept of memory consolidation in REM sleep. For instance, what is the functional meaning of the REM sleep increase after immobilization stress or learned helplessness? What sort of information is it so necessary to consolidate by means of REM sleep after such an experience? The subject needs only to overcome the unproductive state of renunciation of search elicited by these conditions. This means that the concept of the indirect positive role of REM sleep in memory functions seems to be more comprehensive and broad.
This concept also allows explanation of some data showing that REM sleep has a double effect on retention: facilitative and inhibitory 169. Latash and Manov 167 have performed an investigation on the task of declarative memory. Human subjects were awakened in the first or second cycle in delta sleep close to REM sleep or after the first or second episode of REM sleep. Every subject passed all four experimental conditions, but every night each subject had only one awakening, during which he was tested for the amount of retention of material he had learned before going to sleep. The authors found that retention after the second REM sleep episode was lower than immediately before this episode. The addition of a short period of time that corresponds to the second REM sleep period had an unexpected inhibitory influence on the declarative memory retention. At the same time, REM sleep facilitated the positive effect of SWS on retention. From my point of view, this facilitative effect was indirect and can be explained as an outcome of the general positive effect of REM sleep on mental state due to the restoration of search activity. A direct negative effect of REM sleep on retention may be due to the interference between dream images and learned material. This double effect of REM sleep may explain the different outcomes of REM sleep deprivation in different conditions. If the learning process per se causes renunciation of search, the requirement in REM sleep has to be particularly high and REM deprivation will inhibit retention. If the learning process stimulates search activity, REM sleep deprivation may sometimes even facilitate retention.
In addition, by accepting this concept, some other contradictions are avoided. As mentioned above, there are data that declarative memory tasks depend on SWS while procedural memory tasks depend on REM sleep. Of course, there are differences between some substantial aspects of declarative and procedural memory tasks - for instance, procedural tasks are more complex and the subject is less prepared for such tasks and this can cause giving up (renunciation of search) during training. However, it is difficult to imagine that these two sorts of task are even opposite according to the essential process of information retention and memory consolidation and that they are related to the opposite directions of flow of information.
It was shown recently 181 that several brain areas activated during the execution of a serial reaction time task during wakefulness were significantly more active during REM sleep in subjects previously intensively trained on the task than in non-trained subjects. In addition, this task was performed better after sleep than before sleep. According to the authors, these results support the hypothesis that memory traces are processed during REM sleep in humans. However, the same brain structures may be involved in search activity during training in wakefulness as well as in REM sleep, and these data can be explained without ascribing to REM sleep a direct participation in memory function. On the other hand, it was shown 182 that dreams may represent, in a very direct way, the previous waking experience and problems the subject was preoccupied with in previous wakefulness. If subjects have been involved in task performance (and even periodically failed in this performance) they can imagine this task in dreams and the relevant brain area may be activated during such imagination, as happens during the imagination in wakefulness. Does it really mean that such imagination contributes to memory consolidation? It seems to be very doubtful because usually people do not see in their dreams any elements of information they have to consolidate in their memory.
The outcome of REM sleep deprivation before training on memory function deserves a short special discussion. A long REM sleep deprivation on the wooden platform before learning destroys simple active avoidance 185, while a short REM deprivation can even stimulate active avoidance 26. If REM deprivation is short, then search activity is frustrated, but brain monoamines and physiological mechanisms responsible for search activity are not yet exhausted. The change from the frustrating conditions on the wooden platform to the conditions of learning and testing may cause a rebound of motor activity and search activity 4. Such new conditions can even promote some forms of learning, for instance, active avoidance. Conversely, if REM deprivation is prolonged, a renunciation of search activity appears, and the whole process of learning is destroyed. Memory traces then become more sensitive to disturbing influences. Thus, REM sleep deprivation before learning creates distress that can interfere with memory.
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