AN INTEGRATIVE PSYCHOPHYSIOLOGICAL APPROACH TO BRAIN HEMISPHERE FUNCTIONS IN SCHIZOPHRENIA

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Publication Date:
February 28, 2013

Neurocience and Biobehavioral Review, Vol. 18, No. 4. pp. 487-495, 1994 Copyright 11

Vadim S. Rotenberg

E-mail: vadir@post.tau.ac.il

Received February 1993

The present paper proposes a new psychophysiological approach to the genesis of positive and negative schizophrenic symptoms. According to this approach, the initial factor in schizophrenic disorders is a functional insufficiency of the right hemisphere which can be determined by early emotional experience in combination with subtle brain damage. This functional insufficiency causes (a) the inability to grasp and select information before its realization; and (b) the inability to produce a polysemantic context which is crucial for creativity, psychological defense, and the restoration of search activity, all of which determine psychophysiological adaptation to the environment. Right hemisphere insufficiency causes left hemisp'ficre hyperactivity as an ineffective attempt to compensate for this functional deficiency. As a result, normal search activity is replaced by artificial search activity which is represented by "positive" symptoms, and which uses the predisposition of the left hemisphere's catecholamine system for its increased activity. The suggestion is made that cognitive impairment in schizophrenia (the inability to use appropriate previous information in relation to current perceptual input) is related to the competition between information processing which requires left hemisphere activity, and the formation of positive symptoms, also based on ieft hemisphere activity.

INTRODUCTION

The role of different factors in the pathogenesis of schizophrenia remains unclear, ambiguous, and controversial. The aim of this presentation is to integrate data on brain hemisphere functions in schizophrenic patients, to compare these data to the clinical picture, and to explain them in the context of the Search Activity Concept (81), which displays a broad and holistic psychophysiological approach to behavior, adaptation to the environment, body resistance, REM sleep functions, and brain catecholamine (CA) metabolism. Search Activity Concept is useful inasmuch as it brings together different topics, each of which is usually discussed separately in relation to the problem of the pathogenesis of schizophrenia. Therefore, in this introduction I shall present the main assumptions of this concept as well as a short critical review of the modern theories of brain hemisphere asymmetry.

Search activity is defined as activity that is oriented to change the situation (or at least the subject's attitude to it) in the absence L-F a precise prediction of the outcome of such activity but taking into consideration real outcomes at all stages of activity. Search activity is represented in different forms of behavior: active self-stimulation in animals, creative behavior in humans, as well as outward oriented, exploratory and active defense (avoidance and fight/flight) behavior in animals and humans. Renunciation of search is the opposite psychobiological state that encompasses neurotic anxiety and depression in humans and freezing in animals, as well as panic and stereotyped behavior. One of the best indicators of search activity in animals is a high amplitude and well organized hippocampal thetarhythm: all forms of behavior that are accompanied by hippocampal thetarhythm (orienting, training, 1; 106; organized arbitrary movement in searching for food and for escape, 103; planned behavior, 53, directed attention, 40, startle reaction, 38) include search activity. Conversely, theta-rhythm is absent during freezing, which reflects the reaction of surrender, as well as during stereotyped consummatory behavior with a definite predictability of outcome (e.g., during the performance of an unconditioned reaction) (38).

Search activity and renunciation of search display an opposite influence on body resistance to the development of psychosomatic disorders in stressful conditions: search activity increases it while renunciation of search decreases it (88,90,91). These two different states also have an opposite influence on steep structure: search activity decreases REM sleep requirement while renunciation of search increases REM sleep requirement (84,89). It is suggested that REM sleep represent a special kind of covert search activity. REM sleep is a mechanism that permits compensation for the biologically and psychologically harmful state of renunciation of search and ensures the restoration of search activity (for detailed arguments see 81,85,87,94).

A high level of trait anxiety, frustration of requirements, fixation on obstacles, a high level of the motivation to avoid failures -all these factors predispose healthy subjects to the rentihciation of search in artificial stressful conditions (92).

There are reasons to believe that the brain monoamine systems are closely connected with search activity. The locus coeruieus, a basic element of the brain noradrenergic system, at the same time performs a most important function in the organization of different forms of search behavior in wakefulness (fight/flight) as well as in sleep (73). In the waking state, norepinephrine cells are exquisitely responsive to all occurrences in the environment to which the organism responds (5). Norepinephrine mediates selective attention (61) and selfstimulation (34). It was suggested that the major function of norepinephrine is sensory arousal in a new situation (orienting response-71, which includes search activity). The general function of dopamine activity in appetitive behavior is to promote the expression of motivational searching for and expecting rewards (71).

Depressive-like behavior caused by unavoidable punishment beyond the animal own control is observed only in the case of a drop in the brain CA level (65). The prevention of the brain norepinephrine depletion (aided by MAO inhibitors) increases stress resistance and restores the animal's ability to exhibit coping responses to stress (50). It was convincingly proved (4) that if the aversive stimuli induce coping behavior, which includes search activity (see 87), this is accompanied by an intensified utilization and-synthesis of CA. When such behavior is impossible (renunciation of search) the utilization of amines intensifies, exceeding their synthesis. This utilization is caused by the increased emotional tension (panic, anxiety) which corresponds to renunciation of search.

Recently the following hypothesis has been developed (81,83,87): search activity can start in the presence of a certain critical level of brain monoamines which are utilized in the course of search behavior. However, search activity itself, once it begins, further stimulates the synthesis of these brain monoamines and ensures their availability. During renunciation of search such positive feedback system does not function, and monoamine expenditure increases in rate. Monoamine functioning forms a vicious circle, since renunciation of search leads to a drop in the brain catecholamine level, which in turn leads to renunciation of search.

The science of brain hemisphere functional asymmetry has a complicated history and in this paper we are going to present only a short review of the most important concepts in this area, which will be concluded by our own approach to the problem.

According to the results of the first investigations performed by Sperry and his co-workers on split-brain patients (33,97) it was suggested that the right and the left hemisphere process qualitatively different information. The function of the left hemisphere is the handling of verbal material, of signs and symbols which ensure verbal communication. The function of the right hemisphere is the handling of nonverbal material: the perception of images, melodias, intonations; space and body position orientation; Field dependence; identification of complicated patterns (like human faces) and the performance of kinaesthetic functions (49,98).

These conclusions, made on the basis of functional analysis of the split brain, corresponded to the results of clinical observations. Left hemisphere strokes cause speech disorders (46). On the other hand, damage to the right hemisphere may cause upset of the body scheme, spatial disorientation, misidentift cation of events and faces, deterioration of the musical ear, as well as decline of creative abilities in a wide range of fields including painting, poetry, music, chess-playing, and nontrivial solving of mathematical problems (14,19,25,1 15).

With the presentation of space-image perceptual tasks, the testee first turns his eyes left at the very onset (an indicator of the activation of his right hemisphere), while in the handling of simple arithmetic and phrase-construction tasks the first involuntary eye movement is to the right [a sign of left hemisphere activity (52)].

All these data seem to confirm the functional difference between hemispheres as a difference between processed information. However, many other data refute this point of view as too simplified:

I . In split-brain subjects, the right hemisphere is able to process verbal constructions if they are not too complicated (26,76). Moreover, it has been demonstrated that proverb interpretation is a function of the right hemisphere (8), as is sense of humor (107) and processing of metaphors (I I 1).

2. EEG activity of the right hemisphere predominates during reading stories, while EEG activity of the left hemisphere predominates during reading textbooks in science (68); however, both belong to verbal information.

3 . The right car (i.e., the left hemisphere) of healthy subjects dominates the perception of dichotically presented melodies if they differ only in rhythm (37). However, all kinds of melodies belong to nonverbal information.

4. Split-brain subjects are periodically able to report their dreams (48), although the dream is usually a visual experience.

5. The left hemisphere in some conditions may be more accurate even in the identification of faces, if they contain some definite outstanding features, like a very long nose etc. (72).

6. Deaf and dumb sign language is nonverbal in its nature, but is localized in the left hemisphere and is damaged by left hemisphere stroke (7).

Thus, it is necessary to suggest that the verbal/nonverbal sdichotomy is inadequate for gaining an insight into the actual and specific features of hemispheric activity.

Another formulation suggests a temporally organization of information in the right and left hemispheres (37). According to this concept, the basic function of the left hemisphere is a consecutive analysis of information, whether verbal or nonverbal while the function of the right hemisphere is a singlestage processing of many elements of information as an unitary whole. This makes possible rapid single stage grasping of the essence of an object or phenomenon even before it is analyzed. This concept is much more fitting as it partly reflects real relationships between brain and reality.

However, it was shown (75) that the left hemisphere is also able to grasp a series of data simultaneously, and as rapidly as the right one, but only if the differences between the elements of such a series are very definite and easily expressed. If these differences are vague and indefinite being dependent on many interrelations between elements, the advantage is on the right side. For instance, the right hemisphere exceeds the left one in the identification of normal faces, but if a face has an out standing and definite feature the left hemisphere can do this task better and more rapidly.

By taking into consideration all the abovementioned data and contradictions, we have suggested that in its most general form, the difference between the two strategies of thinking is reduced to opposite modes of organizing the contextual connection between elements of information. "Left-hemisphere" or formal logical thinking so organizes any sign material (whether symbolic or iconic) as to create a strictly ordered and unambiguously understood context. Its formation requires an active choice, from the many real and potential connections between the multiform objects and phenomena of a few definite connections which would not create internal contradictions, (would be the most natural, and would facilitate an ordered analysis). Such a strategy of thinking makes it possible to build a pragmatically convenient but simplified model of reality. It is based on probability forecasting and a search for concrete cause-and-effect relations, and it is precisely for this model that the vector of time orientation exists.

In contrast, the function of right-hemispheric or image thinking is a simultaneous "capture" of an infinite number of connections and the formation due to this capture of an integral but ambiguous context. In such a context, the whole is not determined by its components since all specific features of the whole are determined only by interconnections between these parts. On the contrary, any concrete element of such a context bears a determining stamp of the whole. A new experience is incorporated in this holistic picture of the world. Individual facets of images interact with each other on many semantic planes simultaneously. Examples of such contextual connections are the connections between images in sleep dreams or in work of art. The advantages of this strategy of thinking manifest themselves only when the information itself is complex, internally contradictory and basically irreducible to an unambiguous context (79,80,82,86).

According to the results of our investigations (93), it is only the organization of the monosemantic left hemispheric context that required the additional nonspecific activation of the brain from the reticular formation. This conclusion is in agreement with data suggesting that the left hemisphere has stronger connections with the brain stem reticular formation (35). The formation of the polysemantic context produced by the right hemisphere does not require additional efforts in subjects who are initially prepared for such activity, as, for instance, in creative persons (60) because the polysemantic context is characterized by numerous connections between "facets" of things and phenomena. The amount of connections is not going to be artificially restricted which requires a lot of efforts. The organization of the polysemantic context does not require additional activation of the brain (23,93): in the process of the creation of the polysemantic context alpha-index in the right hemisphere does not decrease. At the same time brain activation cannot compensate for the functional insufficiency of image thinking in neurotic patients and in subjects with an incomplete lateralization of speech (I 13). The additional activation of the brain in subjects with predominately left hemisphere functions during the solution of right hemisphere tasks displays the insufgcient efforts of the brain to overcome the obstacles produced by weakness of image thinking (91,93).

The flexibility of image thinking makes this mode of thinking very important in task solutions and especially in the resolutions of contradictions. The domination of image thinking in dreams may help them to maintain search activity even in those conditions in which the monostmantic mode of thinking is useless (82,85,87). It explains the role of REM sleep in the restoration of search activity and makes a bridge between the Search Activiiy Concept and the brain hemisphere asymmetry concept.

EVIDENCE OF RIGHT HEMISPHERE DYSFTINCTION IN SCHIZOPHRENICS

One of the most common signs of schizophrenia is the peculiarity of nonverbal behavior which is sometimes even used as a diagnostic criterion (78). Schizophrenic patients often show motor coordination problems and clumsiness. However, motor coordination and the grace of performance of nonverbal behavior as a whole are under the control of the right hemisphere (98).

Nonverbal behavior reflects the deeper levels of personality: it is possible to use a person's nonverbal behavior in dance for an assessment of his/her emotional problems, and also to correct them in dance therapy (2).

The control of such nonverbal behavior may be closely related to self image. Self-image, as every polysemantic image, is localized in the right hemisphere (80). Thus, clumsiness, awkwardness, and motor uncoordination may be considered as signs of right hemisphere dysfunction. This suggestion is confirmed by findings that the "intention" to perform movements either of left or of right extremities is controlled by the right hemisphere (15), and that stroke in the right emisphere makes it difficult for a subject to differentiate self from other (20). There is additional support for this viewpoint; for instance, a higher percentage of nonrighthandedness among schizophrenic patients, in comparison to healthy subjects (43). It means the higher incidence of incomplete lateralization in schizophrenia. But the incomplete lateralization of functions determines also the relative functional insufficiency of both hemispheres, and especially of the right one (113).

A second sign of right hemisphere dysfunction in schizophrenic patients is their difficulty in grasping information immediately before the latter is processed in the left hemisphere (55). Healthy subjects are able to grasp information as a holistic image, without analyzing details; this is suggested to be a function of the right hemisphere which assumes a dominant role in attention across both visual fields (110). This was confirmed in psychophysiological investigations (56): in healthy persons an evoked potential (P300,) appears first in the right hemisphere with the presentation stimulus, including a verbal one. However, schizophrenic patients do not demonstrate such right hemisphere priority (55). The ability to process information unconsciously in the right hemisphere greatly facilitates development of sophisticated psychological defense mechanisms (80). Absence of this ability in schizophrenic patients could underlie their use of primitive defense mechanisms (projection, denial, distortion) and would be consistent with a dysfunctional right hemisphere.

Schizophrenic patients often show inability to form a holistic picture of the world and of complex situations. They perceive the world as a sum of numerous disconnected events or objects (17,39). Such perception, as well as poor powers of reality testing and impaired real-world knowledge (21), characterize right hemisphere dysfunction. The ability of schizophrenic patients to process spatial information is decreased (18,20) even when such information is presented directly to the right hemisphere (43). When schizophrenic patients were asked to label the emotions expressed in magazine photographs of a number of faces, they were less accurate than normals (36,102). Similarly, schizophrenics identified less accurately than normal persons, which emotion was being expressed in nonsense sentences (101). Schizophrenic patients underestimate the intensity of negativeness of expressed negative emotions (6). In healthy subjects the identification of emotional tone of human voice, and especially the identification of negative emotional tone, is a function of the right hemisphere (98).

In the context of all the above mentioned data, it is worthwhile to interpret the data of La Russo (57). In his experiment, paranoid-patients and normal subjects had to judge whether the person presented on videotape expected to receive, according to signal stimulus, a genuine electric shock or a simulated one. Paranoid patients demonstrated significantly higher accuracy than normals for genuine stimuli, while normal subjects were more accurate for simulated stimuli. The author (57) concluded that paranoid patients are highly sensitive to genuine nonverbal facial cues that communicate a particular stress. However, if patients are really more sensitive to nonverbal cues it is necessary to explain what makes them less accurate in identification of simulated nonverbal cues. It should also be noted that normal subjects were more accurate for simulated stimuli than they were for genuine stimuli, while patients were not. This means that normal subjects are more flexible in their reactions, and being more sensitive to nonverbal cues as a whole (according to their reaction to simulated stimuli), they are also more sensitive to genuine stimuli; however, the latter, being emotionally significant, require them to use defense mechanisms which help to underestimate the genuine signal, thus preventing their feeling of empathy from being frustrated. Paranoid patients are less sensitive to nonverbal cues in general and do not use their defense mechanisms. Thus the real question is not why are paranoid patients more accurate in their reactions to genuine stimuli (because they are equally accurate for genuine and simulated stimuli) but why are normal subjects less accurate to genuine stimuli. This point of view is confirmed by the finding that patients proved to be significantly slower than normals in responding to simulated stimuli whereas no difference was found between the two groups for genuine stimuli. It means that normals became slow in responding to genuine stimuli, and such a delay can reflect an interference by defense mechanisms. Thus, it appears that paranoid patients, as well as all schizophrenics are less sensitive to nonverbal cues.

It is possible to suggest that some negative symptoms of schizophrenia reflect functional insufficiency of the right hemisphere. Thus, affective blunting (flattened affect) may be a sign of right hemisphere dysfunction because affective reaction to reality as well as appropriate perception of the expression of affect of other subjects are skills of the right hemisphere (10,62). Visuospatial and visuomotor behavior is disturbed in schizophrenics with negative symptoms (54). Focal damage of the right hemisphere produces phenomena remarkably like those seen in schizophrenia poor appreciation of social nuances, impaired use of prosody, a tendency toward over categorization of objects and incorrect proverb interpretation (20). Deficits in interpersonal behavior such as facial expressiveness or eye contact may be manifestations of a right hemisphere lesion (9). Schizophrenics with negative symptoms demonstrate reduced left-ear advantage on nonverbal dichotic tasks (70).

Disorganization of the affective process, as well as disorders of the form,of thought and poverty of speech content, correlates with right'side ventral prefrontal abnormality (50).

The authors stressed that although formal thought disorder is a cardinal feature of the disorganization syndrome in schizophrenia, the preponderance of frontal perturbations is on the right side of the, brain. It is possible to explain this by our concept that the right hemisphere is responsible for the integrbtion of information in the holistic polysemantic context. The inability to produce such context must lead to the disorganization of thought processes. The inability of the right hemisphere to grasp and estimate information prior to its conscious awareness and to select information according to its relevance may causes the overwhelming of consciousness by irrelevant or even inappropriate information.

Disturbance of associations reflects the inability to create a polysemantic context, which, according to numerous relationships, brings together many different, but naturally related, objects and events. Schizophrenic patients have difficulties in contextual learning (39). According to Chapman et al. (12), chronic schizophrenics, when presented with a word that has several meanings, ignore contextual cues provided in a sentence and choose the strongest (statistically strongest) meaning of the word. From my point of view, this reflects the weakness of the right hemisphere which normally is flexible and does not select the strongest meaning. Probability forecasts which determine the use of the strongest meaning, are a function of the left hemisphere. Delusional patients focus more often on stimuli that are strong or prominent, neglecting weaker stimuli (13). This is consistent with the suggestion that delusions, as well as hallucinations, reflect hyperactivation of the left hemisphere (see below). At the same time, the right hemisphere is especially sensitive to weak and subtle stimuli with a low rate of occurrence (63).

Schizophrenic patients often perceive their own willed actions as being determined from outside (32). It is reasonable to speculate that such phenomena reflect the separation of subject's own willed acts from his Self-image. In this condition, willed acts are regulated by the left hemisphere in the same manner as the acts of a robot without subjective identification with his own acts. It is possible to compare this phenomenon to the common subject's feeling after a right hemisphere stroke-a feeling that movements of his extremities (and especially left extremities) do not belong to him.

Ambivalent behavior may be also a result of the disturbed Self-image. If willed actions and wishes are perceived as being determined from outside, the subject has to feel ambivalent attitudes to most of his acts and desires. It has been shown that right hemisphere damage is more likely to result in delusions (18,28). This confirms the role of the right hemisphere in information selection.

Some recent investigations confirm the role of the right hemisphere dysfunction in the genesis of negative symptoms. The latter are accompanied by the hypometabolism in the right dorsolateral convexity (I 12). In neuroleptic naive patients as well as in patients with chronic schizophrenia, decreased activation in the right parietal cortex is combined with typical symptomatology (3). Never medicated schizophrenic patients had higher left than right hemisphere metabolic rates in the temporal lobe, while normal controls had higher right than left metabolic rates (I 1,44,45).

Of course, it would be a simplification to relate all negative symptoms to right hemisphere dysfunction. There are many data suggesting that left hemisphere dysfunction is also all important factor in producing negative symptoms, especially after the disappearance (exhaustion?) of positive symptoms (42,96). However, it is necessary to stress that even when the nature of the thought and speech disorders is discussed, data on the left hemisphere dysfunction are usually combined with data on right hemisphere dysfunction (58,96). It is possible to suggest that right hemisphere insufficiency produces a general predisposition to schizophrenic disorders (negative), while predominance of negative orpositive symploms in the clinical picture depends more on left hemisphere activity (to be discussed later).

POSSIBLE REASONSFOR RIGHT HEMISPHERE INSUFFICIENCY

There are different possible reasons for the right hemisphere dysfunction. First of all, it may be an organic brain disorder, inherent or acquired in early childhood. It was found that enlarged ventricles and decreased brain weight are associated with abnormalities of cognition, personality and social functioning in childhood, and such abnormalities are precursors of the adult negative syndromes (74). It was also shown (29) that schizophrenia with many negative symptoms is associated with poor premorbid functioning. However, we are not going to overestimate organic brain disorders, and especially organic right hemisphere disorders as a main source of right hemisphere dysfunction. Brain functions in early childhood are very flexible, and the adaptability of the brain is high enough to overcome mild or moderate organic damage. Since the right hemisphere is organized as a neural network with numerous duplications of functions (I 15), it is especially resistant to organic damage in early childhood. For this reason, organic brain damage may only cause a nonspecific predisposition to functional insufficiency. The realization of this predisposition depends more on the conditions of the child's development.

We suggest that early education has an especially important influence on right hemisphere activity. So far, this is only a speculation, but a reasonable speculation. It is a common assumption in psychodynamic literature (2,67) that deficient parental emotional support in early childhood and especially lack of emotional contact with the mother, can predispose the subject to mental and psychosomatic disorders by disturbing the "potential space" (67) which is crucial for the development of imagination.

In the context of the present approach, this means that the child is chronically deprived of those meaningful relationships which can develop his ability to organize the polysemantic context. Emotional relationships are polysemantic in their nature: it is difficult to explain logically and express completely why a person loves or hates somebody. Emotional relationships are based on numerous connections between subjects, and these connections being disposed in different semantic planes cannot be covered by monosemantic notions. It is possible to express emotions in art because art is also polysemantic in its nature. From this point of view it is easy to explain why only the right hemisphere is able to discriminate emotional expressions (22,62). It means that emotional relationships are the most effective and natural way to develop the right hemisphere's ability to form polysemantic context, especially in early childhood, when the potential resources of right hemisphere are high enough (98). However, it means also that the deprivation of natural emotional relationships prevents the development of the ability to create polysemantic context.

Another possible reason for the suppression of right hemisphere functions is the peculiarity ofschool education in Western culture. This education is oriented almost exclusively to the development of left hemisphere functions (91). Most of the tasks presented to pupils are based on logical monosemantic rules. In most cases neither children nor adolescents use tasks which require creativity or unusual ways of thinking. As a result, right hemisphere functions are not trained and can be repressed. In the context of,this approach, it would be interesting to compare the psychophysiological peculiarities of schizophrenics in Western and Eastern countries, according to their right hemisphere ability.

LEFT HEMISPHERE HYPERACTIVATION

As was shown above, right hemisphere ability to create as well as understand the polysemantic context plays an important role in adaptation, in defense mechanisms, and in the process of integration with the world. If this ability is lost or decreased, the subject has only one option-to increase left hemisphere activity in an attempt to resolve difficult tasks and to overcome obstacles. The functional insufficiency of the right hemisphere determines the attempts of compensatory additional physiological and psychological activation of the left hemisphere, while additional activation of the right hemisphere is ineffective: right hemisphere style of thinking does not require additional brain activation (23) and such additional activation does not help to improve right hemisphere functions (91,93).

This suggestion was confirmed in psychophysiological investigations: subjects who are characterized by a decreased lateralization of functions (incomplete dominance for speech) and by weakness of right hemisphere skills (caused by competition of different functions in the same hemisphere, 30,95, 113) demonstrate a compensatory hyperactivation of the left hemisphere not only in the process of logical thinking, but also in the process of decision-making in nonverbal tasks which principally require competence of the right hemisphere (I 13). Such additional left hemisphere hyperactivity is accompanied by an increased mimetic muscle tension probably due to the close connections between the left hemisphere and the brain stem activating mechanisms. The brain attempts to do its best by mobilizing all resources, but without real success.

The ability to create a polysemantic context is an important link in the maintenance and restoration of search activity (82), as well as in information selection and in the protection of consciousness from the disorganized stream of information. If this link is lost there is increased requirement for left hemisphere activity which usually requires additional physiological activation (93). The left hemisphere creates an artificial explanatory system, in the form of delusions, paranoid ideas and verbal hallucinations, and this explanatory system has to displace the natural ability to grasp reality as a whole and to overcome contradictions in the process of grasping (right hemisphere function). Thus, search activity is based totally on the exaggerated left hemisphere functions. Positive feedback between search activity and brain catecholamines helps to maintain search activity and even to increase it (see above). The left hemisphere is naturally predisposed to become such a closed self-determined system according to the catecholamine distribution in the brain (the activity of the dopamine system of the left hemisphere is higher than that of the right one dopamine pathways favor the left hemisphere over the right (77,100). The number of dopamine receptors is increased in left subcortical structures (108), making the left hemisphere more sensitive to the dopamine.

The functional hyperactivation of the left hemisphere in schizophrenia is confirmed in many investigations. In unmedicated schizophrenic patients, increased left hemisphere blood flow and metabolic activity is combined with reduced blood flow and metabolic activity in the right hemisphere (44,45,58).

Some EEG data strongly confirm left hemisphere hyperactivation in schizophrenic patients (43). Psychosis-prone students demonstrated a significantly exaggerated right-ear advantage and reduced left-ear advantage on a consonant-vowel task (69).

Thus, on the one hand, brain CA systems afe more active in the left hemisphere and supply search activity. On the other hand, left hemisphere is functionally more active in schizophrenia, and positive symptoms are related to this left hemisphere activity (58,96). At the same time, according to the well known monoamine conception of schizophrenia (see 39,99) the appearance of the positive symptoms is determined by the hyperactivity of brain CA systems (dopamine, norepinephrin,l!), and the beneficial effect of neurolepties in reducing positive symptoms is based on the blocking of dopamine receptors of the limbic system of the brain. Parkinsonian-like disorders caused by neurolepties are considered to be a side effect of the impairment of brain CA activity. By taking into consideration all these data, it is possible to suggest that positive symptoms may represent an intensive but irregular and misdirected search activity, which tries to compensatefor the right hemisphere insufficiency.

Hyperactivation of the left hemisphere may result in misdirected search activity precisely because the left hemisphere is able to create an artificial world disconnected from reality (86). Schizophrenic patients may be predisposed to left hemisphere hyperactivation due to dysregulation and instability of brain CA release and metabolism (104). The following reasons suggest that positive symptoms are representative of misdirected search activity:

1.Paranoid behavior and hallucinations are examples of search activity: both are active behaviors (at least active perceptive behaviors) without definite promise of results. A subject never can be sure about future events in his artificial world or about outcomes of his own interaction with this world. At the same time the subject remains highly sensitive to all events and outcomes, which also is consistent with the definition of search activity.

2. Aggravation of psychotic symptoms is accompanied by a reduction of REM sleep requirement: REM sleep is reduced without a subsequent rebound effect (64). This is a typical pattern of increased search activity (81,84). On the other hand, neuroleptic treatment leads to an increase in REM sleep. Being neuroleptic-free, patients demonstrate a decrease of REM sleep in parallel with the increase of positive symptoms (66).

According to the search activity concept brain CA overactivity being a main biological marker of positive schizophrenic symptoms is not to be understood as a cause of psychotic symptomatology but rather as a correlate of intensive search activity. Neuroleptics reduce search activity and remove positive symptoms. In our previous investigation (88), we established that the artificial extrapyramidal syndrome caused by neurolepties is more prominent and appears more rapidly in a state of freezing (renunciation of search). Active avoidance or self-stimulation of the lateral hypothalamic nucleus, led to reduction and delay of this neuroleptic syndrome. Thus, neuroleptics may produce the general predisposition for the development of the neuroleptic syndrome by blocking brain CA receptors and, consequently, by blocking search activity. That's why the restoration of search activity can prevent the development of this syndrome. It may also explain the "paradoxical kinesia" in the parkinson-like disorders in the face of sudden activating events (91).

There are some contradictions in the relationship between positive symptoms, catecholaminergic overactivity and latent inhibition: latent inhibition correlates better with dopaminergic overactivity find with the acuteness of the disease than with positive symptoms (38). This contradiction can be resolved by assuming that "true" positive symptoms include only irregular search activity, while stereotyped delusions and hallucinations in chronic patients do not belong to this description and do not correlate (negatively) with latent inhibition.

The hypothesis of the left hemisphere hyperactivation as an attempt to compensate for the functional disability of the right corresponds to experimental data presented by Gur (43), as well as to some general ideas of Venables (105). It is also in agreement with studies which stress the role of the left hemisphere hyperactivity in the production of positive symptoms paranoid ideas, verbal hallucinations and delusions (24,41,42, 58,96). The "hyperpriming" effect on a series of lexical decision tasks in schizophrenia (59) confirm patients increased ability to expect signals according to the probability forecast, which is the function of the left hemisphere (63). It was shown that the more the stimulus material is predigested or structured, the better the performance of schizophrenic patients becomes (16), and it is also in agreement with the left hemisphere hyperactivity, because exactly left hemisphere works better with structured material.

EXPLANATION OF PARADOXES

By accepting the concept of left hemisphere compensatory hyperactivity we have to explain data that seem inconsistent with this conception. The main paradox is that the physiological and functional hyperactivity of the left hemisphere is combined with inability to perform psychological functions controlled by the left hemisphere. Recent psychological investigations have led to the conclusion that the common feature in information processing of schizophrenics with predominantly positive symptoms is their inability to use appropriate previous information in relation to current perceptual input (47). The inability to form the appropriate monosemantic context by using relations between past and current information is a specific feature of acute schizophrenia with positive symptoms. This idea can account for results of many different investigations (see 39): the absence of latent inhibition and the Kamin blocking effect (schizophrenics, in contrast to healthy subjects, are able to find regular connections between information which is relevant to the current task condition but was irrelevant to the previous task condition); the inability to discriminate between relevant and irrelevant information (many schizophrenics with positive symptoms display either the absence of habituation to the orienting reaction, or the absence of the orienting reaction from the very beginning of stimulation (51). These two types of reaction seem to be contradictory only in the face of it. According to the first one, every signal, even if it is meaningless and irrelevant, becomes meaningful and relevant to the subject. According to the second one, every signal, including even the first which is new and unexpected and has to be meaningful, remains meaningless as if it had already been presented many times. The inability to discriminate between relevant and irrelevant information means that the subject does not compare current information to the previously formed model of reality and does not include new information in this model which determines the estimation of the new information as being relevant to the task or not. The absence of the probability forecast (the absence of the Sharpantje illusion, 27) confirms the inability to use previous information.

However, the inability to make a model of reality reflects dysfunction of the left hemisphere. Probability forecast is a function of the left hemisphere (63,114), as is the estimation of regularities of previous input. Thus, paradoxically, the hyperactive left hemisphere performs its own functions ineffectively.

But it is possible to resolve this paradox. If the left hemisphere is involved in manipulation of the artificial world created by this hemisphere (with delusions, compulsive ideas, hallucinations) than the skills of the left hemisphere are not used in the process of adaptation to the real world. According to Frith (3 1) schizophrenics perform tasks as if they have other task competing for their attention. And they really have! One might predict that if the information presented in mental tasks is relevant to the context of hallucinations and delusions, this information will be used much more effectively.

The present conception helps to propose a new approach to an old problem the similarity and difference between genius and madness. Creativity is based on the ability to be free, if necessary, from previous information and to overcome a restricted model of reality. However, to be able not to use information is not the same as to be unable to use it (86), due to the decreased functional efficiency of the right hemisphere, combined with the preoccupation of the left hemisphere by positive symptoms.

In the context of our conception it is worthwhile to discuss the animal model of schizophrenia caused by amphetamine administration.

Amphetamine abolishes latent inhibition while neuroleptics restore it, and it seems to be similar to what happened in human schizophrenia (109). This phenomenon can be explained without using the concept of the probability forecast: it is possible to suggest that the general brain hyperactivity (caused by the stimulation of the brain CA metabolism by amphetamine) increases the subjective relevance of the irrelevant stimulus. However, this phenomenon is not specific for schizophrenia. It is typical also for the increased emotional tension, for general anxiety which is not accompanied by positive symptoms while in schizophrenia the disturbance of the latent inhibition mostly characterizes patients with positive symptoms (39). The animal model cannot explain the absence of the Sharpantje illusion in schizophrenic patients, while our approach helps to explain the absence of this illusion in the same paradigm as the absence of latent inhibition according to the inability to form the relevant model of reality. Thus, although increased emotional vulnerability can change the irrelevant stimulus into the relevant one, this mechanism is not enough to explain the peculiarities of schizophrenic disorders.

SUMMARY

According to the present model of the pathogenesis of schizophrenia, the crucial point in the development of this disorder is not hyperactivity of the left hemisphere (although the latter may be based on an inherent predisposition of the brain CA system), but rather the hypofunction of the right hemisphere. It is the right hemisphere that determines the harmonic integration of the person in the polysemantic world and a normal development of self-image. It suggests that early education and the organization of appropriate social (emotional) relationships in early childhood and orientation the school education toward the development of right hemisphere functions may be crucial in the preventing emergence of schizophrenic disorders, and the treatment of schizophrenia requires the activation of right hemisphere abilities.

My best thanks to Dr. R. Greenberg and Dr. Ch. Pearlman for revising of this paper.

REFERENCES

1. Adey, W. R. Hippocampal states and functional relations with corticosubcortical systems in attention and learning. Brain Res. 27:228-237; 1967.

2. Ammon, G. Der mehrdimensionale Mensch. Munchen, Pinel; 1986.

3. Andreasen, N. C.; Rezai, K.; Alliger, R.; Swayze, V. W.; Flaum, M.; Kirchner, L.; Cohen, G.; O'Leary, D. S. HypofronWity in neuroleptic naive patients and in patients with chronic schizophrenia. Arch. Gen. Psychiatry 49:943-958; 1992.

4. Anisman, H.; Zacharko, R. M. Depression: The predisposing influence of stress. Behav. Brain Sci. 5:89-138; 1982.

5. Aston-Jones, G.; Bloom, F. E. Norepinephrine-containing locus coeruleus neurons in behaving rats exhibit pronounced responses to nonnoxious environmental stimuli. J. Neurosci. 8:117-190; 1981.

6. Bellack, A. S.; Mueser, K. T.; Wada, J.; Sayers, S.; Morrison, R. L. The ability of schizophrenics to perceive and cope with negative affect. Br. J. Psychiatry 160:473-480; 1992.

7 .Bellugi, O.; Poizner, H.; Klima, E. S. Brain organization for languages: Clues from sign aphasia. Hum. Neurobiol. 2:155170; 1983.

8. Benton, A. L. Differential behavioral effects of frontal lobe disease. Neuropsychologia 6:53-60; 1968.

9. Borod, J. C.; Alpert, M.; Brozgold, A.; Martin, C.; Welkowitz, J.; Diller, L.; Passlow, E.; Angrist, B.; Lieberman, J. A. A preliminary comparison of flat affect schizophrenics and braindamaged patients on measures of affective processing. J. Commun. Dis. 22:93-104; 1989.

10. Bryson, S. E.; McLaren, J.; Wadden, N. P.; MacLean, M. Differential asymmetries for positive and negative emotion: Hemisphere or stimulus effects? Cortex 27:359-366; 1991.

11. Buchsbaum, M. S.; Haier, R. J.; Potkin, S. G.; Neuchterlein, K.; Bracha, H. S.; Katz, M.; Lohr, J.; Wu, J.; Lottenberg, S.; Jerabek, P. A.; Trenary, M.; Tafalla, R.; Reynolds, Ch.; Bunney, W. Fronto-striatat disorder of cerebral metabolism in never-medicated schizophrenics, Arch. Gen. Psychiatry 49:935-942; 1992.

12. Chapman, L. J.; Chapman, J. P.; Daut, R. L. Schizophrenic inability to disattend from strong aspects of meaning. J. Abnorm. Psychol. 85:35-40; 1976.

13. Chapman, L. J.; Chapman, J. P. The genesis of delusions. Delusional Beliefs. Wiley; 1986.

14. Chernigovskaya, T. V.; Deglin, V. L. Brain functional asymmetry and neural organization of linguistic competence. Brain Lang. 29:141-153; 1986.

15. Coslett, H. B.; Heilman, K. M. Hemihypokinesia after right hemisphere stroke. Brain Cogn. 9:267-278; 1989.

16. Cremer, P.; Bowen, J.; O'Neil, M. Schizophrenics and social judgements. Why do schizophrenics get it wrong? Br. J. Psychiatry 160:481-487; 1992.

17. Cutting, J. The psychology of schizophrenia. Edinburgh: Churchill Livingstone; 1985.

18. Cutting, J. The right cerebral hemisphere and psychiatric disorders. Oxford: Oxford University Press; 1990.

19. Cutting, J. Delusional misidentification and the role of the right hemisphere in the appreciation of identity. Br. J. Psychiatry 159(14):70-75; 1991.

20. Cutting, J. The role of right hemisphere dysfunction in psychiatric disorders. Br. J. Psychiatry 160:583-588; 1992.

21. Cutting, J.; Murphy, D. Schizophrenic thought disorder: Psychological and organic perspectives. Br. J. Psychiatry 152:310319; 1988.

22. David, A. S.; Cutting, J. Affect, affective disorder and schizophrenia: A neuropsychological investigation of right hemisphere function. Br. J. Psychiatry 156:491-495; 1990.

23. De Pascalis, V.; Palumbo, G. EEG alpha asymmetry: task difficulty and hypnotyzability. Percep. Mot. Skills 62:139-150; 1986.

24. Early, T. S.; Reiman, E. R.; Raichle, M. E. Left globus pau!dus abnormality in never-medicated patients with schizophrenia. Proceeding of the National Academy of Science. 84:561-563; 1987.

25. Ehrlichman, M.; Barret, R. Right hemispheric specialization for mental imagery: a review of the evidence. Brain Cogn. 2:55-76; 1983.

26. Ellis, A. W.; Yong, A. W., Andersen, Ch. Modes of word recognition in the left and right cerebral hemispheres. Brain Lang. 35: 254-277;1988.

27. Feigenberg, 1. M. Funktionelle Verbindungen der Sensorischen Systeme. In: Norm und Pathologie, Stuttgart, Hippokrates Verlag; 1972.

28. Feinberg, T. E.; Shapiro, R. M. Misidentification-reduplication and the right hemisphere. Neuropsychiatry, Neuropsychol. Behav. Neurol. 2:39-48; 1989.

29.Fenton, W. S.; McGleshan, Th. H. Natural history of schizophrenic subtypes. 1. Longitudinal study of paranoid, hebephrenic and undifferentiated schizophrenics. Arch. Gen. Psychiatry 48:969-977; 1991.

30. Ferris, G. S.; Dorson, N. M. Agenesis of the corpus callosum. 1. Neuropsychological studies. Cortex 11:95-122; 1975.

31. Frith, C. D. Consciousness, information processing and schizophrenia. Br. J. Psychiatry 134:225-235; 1979.

32. Frith, C. R., Done, D. J. Experiences of alien control in schizophrenia reflect a disorder in the control monitoring of action. Psychol. Med. 19.-359-363; 1989.

33. Gazzaniga, M. S. The bisected brain. New York: Apieton; 1970.

34. German, D. C.; Bowden, D. M. Catecholamine systems as the neural substrated for intra-cranial self-stimulation: A hypothesis. Brain Res. 73:381-419; 1974.

35. Geschwind, N. Specialization of the human brain. Sci. Am. CCXLI:180-201; 1979.

36. Gessier, S.; Cutting, J.; Froith, C. D. Schizophrenic inability to judge facial emotion: a controlled study. Br. J. Clin. Psychol. 28:19-29; 1989.

37. Gordon, H. Left hemisphere dominance for rhythmic elements in dichotomically present melodies. Cortex 14:58-70; 1978.

38. Gray, J. A. Precis of the neuropsychology of anxiety. An enquiry into the functions of the septo-hippocampal system. Behav. Brain Sci. 5:469-534; 1982.

39. Gray, J. A.; Feldon, J.; Rawlins, J. N. P.; Hemsley, D. R.; Smith, A. D. The neuropsychology of schizophrenia. Behav. Brain Sci. 14:1-64; 1991.

40. Green, J. D.; Arduini, A. A. Hippocampal electrical activity in arousal. J. Neurophysiol. 17:533-537; 1954.

41. Gruzelier, J. Cerebral laterality and schizophrenia: A review of the interhemispheric disconnection hypothesis. In: Glass, A., ed. Individual differences in hemispheric specialization. New York: Plenum Press; 1987:357-375.

42. Gruzelier, J.; Manchanda, R. The syndrome of schizophrenia: Relations between electrodermal response, lateral asymmetries and clinical ratings. Br. J. of Psychiatry 141:488-495; 1982.

43. Gur, R. E. Left hemisphere disfunction and left hemisphere overactivation in schizophrenia. J. Abnorm. Psychol. 87:226238; 1978.

44. Gur, R. E.; Resnick, S. M.; Alavi, A.; Gur, R. C.; Caroff, S.; Dann, R.; Silver, F. L.; Saykin, A. J.; Chawluk, J. B.; Kushner, M.; Reivich, M. Regional brain function in schizophrenia. Arch. Gen. Psychiatry 44:119-125; 1987.

45. Gur, R. E.; Resnick, S. M.; Alavi, A. Regional brain function in schizophrenia: a position emission tomography study. Arch. Gen. Psychiatry 44:119-125; 1987.

46. Hecaen, H. Clinical symptomatology in right and left hemispheric lesions. In: Mountecastle, V. B., ed. Interhemispheric relations and cerebral dominance. Baltimore: Johns Hopkins Press; 1962:215-47. Hemsley, D. R. An experimental psychological model for

schizophrenia. In: 14afner, H.; Gattaz, W. F., Janzavik, W., eds. Search for the causes of schizophrenia. Springer Veriag; 1987:179-186.

48. Hoppe, K. D. Split-brain and psychoanalysis. Psychoanalytic Quarter. 46:220-248; 1977.

49. Jones, B. Lateral asymmetry in testing long-term memory for faces. Cortex 15:183-186; 1979.

50. Katz, R. J.; Roth, K. A.; Carrol, B. J. Acute and chronic stress effects on open field activity in the rat: Implications for a model of depression. Neurosci. Biobehav. Rev. 5:247-251; 1981.

51. Kim, D. K.; Shin, Y. M.; Kim, Ch. E.; Cho, H. S.; Kim, Y. S. Electrodermal responsiveness, clinical variables and brain imaging in male chronic schizophrenics. Biol. Psychiatry 33:786793; 1993.

52. Kinsbourne, M. Eye and head turning indicates cerebral lateraiization. Science 176:539-541; 1972.

53. Konorski, J.; Santibanez, G.; Beck, J. Electrical hippocampal activity and heart rate in classical and instrumental conditioning. Acta Biologiae Experimentalis 28:169-185; 1968.

54. Kojima, T.; Mitsushima, E.; Ando, K.; Sekurada, M.; Ohta, K.; Moriya, H.; Shimazono, Y. Exploratory eye movements and neuropsychological tests in schizophrenic patients. Schizophr. Bull. 18:85-94; 1992.

55. Kostandov, E. A. The functional asymmetry of brain hemispheres and subconscious perception. Moscow, Nauka publisher (in Russian); 1983.

56. Kostandov, E. A.; Genkina, 0. A. Hemisphere asymmetry of evoked electrical activity of the cerebral cortex to letter and nonverbal stimuli. Zhurnal Vysshey Nervnoy Deyatelnosti 26: 21-29;1976.

57. La Russo, L. Sensitivity of paranoid patients to nonverbal cues. J. Abnorm. Psychol. 87:463-471; 1987.

58. Liddle, P. F.; Friston, K. J.; Frith, C. D.; Hirsh, S. R.; Jones, T.; Frakowiack, R. S. J. Patterns of cerebral blood flow in schizophrenia. Br. J. Psychiatry 160:179-186; 1992.

59. Manschreck, T. C.; Maher, B. A.; Milavetz, J. J.; Ames, D.; Weisstein, C. C.; Schneider, M. L. Semantic priming in thought disordered schizophrenic patients. Schizophr. Res. 1:61-66; 1988.

60. Martindale, C. What makes creative people different? Psychol. Today 7:44-47; 1975.

61. Mason, S. T. Norepinephrine and selective attention: A review of the model and evidence. Life Sci. 27:617-63 1; 198 1.

62. McLaren, J.; Bryson, S. E. Hemisphere asymmetry in the perception of emotional and neutral faces. Cortex 23:645-654; 1987.

63. Meerson, Y. A. Left and right brain hemispheres in the process of the estimation of the probability forecast. Fiziologia Cheloveka 12:723-731; 1986.

64. Mendelson, W. B.; Gillin, J. Ch.; Wyatt, R. J. Human sleep and its disorders. New York, London: Plenum Press; 1977.

65. Miller, N. E. Learning, stress and psychosomatic symptoms. Acta Neurobiol. Exp. 36:141-156; 1976.

66. Nofzinger, E. A.; van Kammen, D. P.; Gilbertson, M. W.; Gurklis, J. A.; Peters, J. L. Electroencephalographic sleep in clinically stable schizophrenic patients: two weeks vs. six weeks neuroleptic free. Biol. Psychiatry 33:829-835; 1993.

67. Ogden, Th. H. On potential space. Intern. J. Psycho-Anal. 66: 129-140;1985.

68. Ornstein, R.; Herron, J.; Johnstone, J.; Swencionis, Ch. Differential right hemisphere involvement in two reading tasks. Psychophysiology 16:398-401; 1979.

69. Overby, L. A. Perceptual asymmetry in psychosis-prone college students: evidence for left hemisphere overactivation. J. Abnorm. Psychol. 101:96-103; 1992.

70. Overby, L. A.; Harris, A. E.; Leek, M. R. Perceptual asymmetry in schizophrenia and affective disorders: implications from a right hemisphere task. Neuropsychologia 27:861-870; 1989.

71. Panksepp, 1. The neurocheniistry of behavior. Annu. Rev. Psychol. 37:77-107; 1986.

72. Parkin, A. J.; Williamson, P. Cerebral lateralization at different stages of facial processing. Cortex 23:99-1 10; 1987.

73. Paul, A. M.; van Dongen. The human locus coeruleus in neurol"gy and psychiatry. Prog. Neurobiol. 17:97-139; 1981,

74. Pilowsky, L.; Murray, R. M. Why don't preschizophrenic children have dellusions and hallucinations? Behav. Brain Sci. 14: 41-42; 1991,

75. Polich, J. M. Hemispheric differences for visual search: serial vs. parallel processing revisited. Neuropsychologia 20:297-307; 1982.

76. Rastatter, M.; Dall, C. W.; McGuire, R. A.; Loren, C. Vocal reaction times to unilaterally presented concrete and abstract words: Toward a theory of differential right hemispheric semantic processing. Cortex 2:135-148; 1987.

77. Reynolds, G. P. Increased concentrations and lateral asymmetry of arnygdala dopaniine in schizophrenia. Nature 305:527-529; 1983.

78. Rosen, A. J.; Lockhart, J. J.; Grants, E. S.; Westergaard, C. K. Maintenance of grip-induced muscle tension: A behavioral marker of schizophrenia. J. Abnorm. Psychology 100:583-593; 1991.

79. Rotenberg, V. S. Word and image: The problem of context. Dynarnische Psychiatric/Dynaniie Psychiatry 59:494-498; 1979.

80. Rotenberg, V. S. Funktionale Dichotomic der Gehirnhemisphcren und die Bedeutung der Suchaktivitat fur Physiologische und Psychopathologische Processe. In: Ammon, G. (Herausgeber) Handbuch der Dynamische Psychiatrie, Ernst Reinhardt Verlag, Munchen, Basel, Bd. 2:275-335; 1982.

81. Rotenberg, V. S. Search activity in the context of psychosomatic disturbances, of brain monoamines and REM sleep function. Pavlov. 1. Biol. Sci. 19:1-15; 1984.

82. Rotenberg, V. S. Sleep dreams, cerebral dominance and creation. Pavlov. J. Biol. Sci. 20:53-58; 1985.

83. Rotenberg, V. S. Anxiety, panicky behavior and depression: A psychobehavioral and biological approach. Dynamic Psychiatry 23:302-309; 1990.

84. Rotenberg, V. S. The influence of the emotional stress on sleep in healthy subjects and in psychosomatic patients. la: Founding Congress of World Federation of Sleep Research Societies, Abstracts, Cannas, 15; 1991.

85. Rotenberg, V. S. Sleep and memory 1: The influence of different sleep stages on memory. Neurosci. Diobehav. Rev. 16:497-502; 1992.

86. Rotenberg, V. S. Richness against freedom: two hemisphere functions and the problem of creativity. Eur. J. High Ability 4: 11-19; 1993.

87. Rotenberg, V. S. REM sleep and dreams as mechanisms of the recovery of search activity. In: Moffitt, A.; Kramer, M.; Hoffmann, R., eds. The functions of dreaming. State University of New York Press; 1993:261-292.

88. Rotenberg, V. S.; Arshavsky, V. V. Search activity and its impact on experimental and clinical pathology. Activitas Nervosa Superior (Praha). 21:105-115; 1979a.

89. Rotenberg, V. S.; Arshavsky, V. V. REM sleep, stress and search activity. Waking Sleeping. 3:235-244; 1979b.

90. Rotenberg, V. S.; Alexeyev, V. V. Essential hypertension: A psychosomatic features or a psychosomatic disease? A differential analysis of cases in terms of search activity concept. Dynamic Psychiatry 68:129-139; 198 1.

91. Rotenberg, V. S.; Arshavsky, V. V. Search activity and adaptation. Moscow, Nauka publisher (in Russian); 1984.

92. Rotenberg, V. S.; Korosteleva, 1. S. Psychological aspects of the search activity and learned helplessness in psychosomatic patients and healthy testees. Dynamic Psychiatry 120:1-13; 1990.

93. Rotenberg, V. S.; Arshavsky, V. V. Psychophysiology of hemispheric asymmetry. The 'entropy" of right hemisphere activity. Integrative Physiol. Behav. Sci. 26:183-188; 1991.

94. Rotenberg, V. S.; Boucsein, W. Adaptive vs. maladaptive emotional tension. Genetic, Social and General Psychology Monographs 119:207-232; 1993.

95. Sauerwein, H.; Lassonde, M. Intraand interhemispheric processing of visual information in callosal agenesis. Neuropsychologia 21:167-17 1; 1983,

96. Silverstein, M. L.; Marengo, J. T.; Fogg, L. Two types of thought disorder and lateralized neuropsychological dysfunction. Schizophr. Bull. 17:679-687; 1991.

97. Sperry, R.; Gazzaniga, M.; Bogen, 1. Interhemispheric relationships: The neocortical comissures, syndromes of hemisphere disconnection. Handbook of Clinical Neurology: Amsterdam; 1969:273-290.

98. Springer, S.; Deutsch, G. Left brain, right brain. New York: W. H. Freeman and Co.; 1985.

99. Swerdlow, N. R.; Koob, G. K. Dopamine, schizophrenia and depression. Toward a unified hypothesis of cortico-striatopallido-thalamic function. Behav. Brain Sci. 10: 197-245; 1987.

100. Tucker, D. M.; Williamson, P. A. Asymmetric neural control in human self-regulation. Psychol. Rev. 91:185-215; 1984.

101. Turner, J. Schizophrenics as judges of vocal expression of emotional meaning. In: Davitz, J. R., ed. The communication of emotional meaning. New York: McGrow-Hill; 1964.

102. Vanderberg, S. G. La mesure de la deterioration de la comprension sociale dans la schizophrenia. Revue de Psychologie Appliquee. 12-189-194; 1962.

103. Vanderwolf, C. H.; Kramis, R.; Robinson, T. E. Hippocampal electrical activity during waking behavior and sleep: Analyses using central acting drugs. In: Elliott, K.; Whelan, J., eds. Functions of the septo-hippocampal system. Ciba Foundation Symposium, Amsterdam, Elsevier; 1978:199-221.

104. van Kammen, D. P. The biochemical basis of relapse and drug response in schizophrenia: Review and hypothesis. Psychol. Med. 21:887-895; 1991.

105. Venables, P. H. Cerebral mechanisms, autonomic responsiveness and attention in schizophrenia. In: Spaudling, W. D.; Cole, J. K., eds. Theories of schizophrenia and psychosis. University of Nebraska Press; 1984.

106. Vinogradova, 0. S. Functional organization of the lymbic system in the process of registration of information: facts and hypotheses. In: Isaacson, R. L.; Pribram, K. H., eds. The hippocampus. Neurophysiology and behavior. New York: Plenum Press; 1975:1-70.

107. Wapner, W.; Hamby, S.; Gardner, H. The role of the right hemisphere in the apprehension of complex linguistic materials. Brain Lang. 14:15-33; 198 1.

108. Weinberger, D. R. Implications of normal brain development for the pathogenesis of schizophrenia. Arch. Gen. Psychiatry 44:668-673; 1987.

109. Weiner, I.; Shofel, A.; Feldon, J. Disruption of latent inhibition by low dose of amphetamine is antagonized by haloperidol and apomorphine. J. Psychopharmacol. 4:255; 1990.

110. Weintraub, S.; Masulem, M. M. Right hemisphere dominance in spatial attention. Arch. Neurol. 44:621-625; 1987.

Ill. Winner, E.; Gardner, H. The comprehension of metaphor in brain damaged patients. Brain 100:717-729; 1977.

112. Wolkin, A.; Sanfilipo, M.; Wolf, A. P.; Angrist, B.; Brodie, J. D.; Rotrosen, J. Negative symptoms and hypofroutality in chronic schizophrenia. Arch. Gen. Psychiatry 49:959-965; kkkjjjjjj1992.

113. Yanson, V. N.; Kenga, Z. F. The dynamic of EEG Alpharhythm and lateralization of speech. Izvestia Akademii Nauk Latviiskoi SSR. 10: 103-107; 1984.

114. Yanson, V. N.; Daya, Z. F.; Jolud, V. A. The relationships between psychophysiological characteristics of probability forecast and functional brain asymmetry. Izvestia Akademii Nauk Latviiskoi SSR. 6:115-119; 1986.

115. Zenkov, L. L'inconscient et la conscience dans l'optique de l'interaction interhemispherique. L'inconscient. La discussion continue, Editions du Progress: Moscow; 1989:241-254.