Ncuropsychologia. Vol. 17, pp. 5S7 to 583. Pergamon Press Ltd. 1979. Printed in Great Britain.

DEDICATED

TO HANS-LUKAS

TEUBER*

IS IT REALLY BETTER TO HAVE YOUR BRAIN LESION EARLY? A REVISION OF THE “KENNARD PRINCIPLE” GERALD E. SCHNEIDER Department

of Psychology, Massachusetts

Institute of Technology,

Cambridge,

Massachusetts,

U.S.A.

Abstract-Redirected growth of the optic tract in hamsters with lesions of the midbrain tectum at birth results in anomalous retinal projections with correlated functional effects; these include a sparing of visually elicited turning responses which are lost after comparable lesions in adulthood. However, the animals sometimes overshoot or undershoot the target, and the responses are slow to be completed. In cases of early unilateral lesions, an optic tract projtction to the wrong side of the midbrain is correlated with turning in the wrong direction in response to stimuli in specific locations. These misdirected movements can be enhanced by reward or suppressed by non-reward, or abolished by surgical section of the abnormal pathway in the mature animal. Principles derived from the experiments with animals allow us to predict that specific lesions in fetal and neonatal humans will cause particular patterns of altered growth of neuroanatomical pathways. These alterations can be expected to cause behavioral anomalies, not only in sensorimotor functions, but also in cognitive functions and in emotional responses and expression; some neuropsychological findings can be interpreted in this manner. HANS-LUKAS TEUBER liked to begin a discussion of early brain injury with a summary of MARGARET KENNARD’S work on the effects of lesions in the motor cortex of baby monkeys

[l--3]: “It is better to have your brain lesion early . . . that is, if you can arrange it!” Many experiments with animals have since confirmed that when the behavioral effects of lesions differ according to the age when they are inflicted, the difference is one of greater sparing of function for the earlier lesion (reviewed by TEUBER [4]). Parallels are easily found for human brain injury [4-71. The greater resiliency of the younger human brain may hold for patients injured at ages as advanced as the mid-20s according to an analysis of several neuropsychological results for wartime head injury cases carried out by W. HURT and TEUBER(see [S]). However, Teuber always went on to describe how experimental and clinical observations of human patients revealed exceptions to the “deceptively simple” view he dubbed the Kennard Principle [4, 9, 10, 111. The degree of functional sparing or loss not only varies with the age at testing and with the specific nature of the test employed, as found also in recent animal experiments [12-181, but some functions appear to be more impaired after the earlier lesions [19-221. Thus, children who have suffered early damage to the cerebral hemispheres may show little of the specific sensory or motor impairments seen in cases of cortical injury in adulthood, but they commonly suffer from a harder-to-define cognitive retardation which is not a characteristic effect of later injury. This type of finding is generally absent from the literature on early lesions in animals, probably due to the narrow focus of behavioral testing. (However, in experiments on hamsters with neonatal lesions of visual *This paper and the following paper continue the series of papers, published in Neltropsychologia 17 (2), dedicated to Hans-Lukas Teuber who died in January 1977.

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cortex, I have noted a severe retardation, relative to the performance of normal animals or animals with lesions at maturity, in initial learning to negotiate a path through a visual discrimination testing apparatus, despite a considerable sparing of pattern discrimination ability by the early lesions [23].) Behavioral observations of humans with early brain injury have revealed more than just quantitative differences from cases of later injury in the degree of sparing or loss of function. Teuber and his colleagues also uncovered some apparently anomalous functions, totally unexpected from studies of adult-injured patients. Thus, they found a group of brain damaged children that appeared to show a genuine hyperesthesia in tests of sensitivity to light touch and of two-point discrimination [24]. In another study, brain-injured children showed a peculiarly deficient ability to walk the paths indicated on visually presented maps: unlike normal children or normal and brain-damaged adults, they avoided diagonal paths [21]. Anomalous motor control has also been found: childhood hemiparesis is accompanied by a high incidence of persistent mirror movements, and these movements are the most evident when the indicators of brain damage appear before the children’s first birthday [25]. The data of the last study noted above, as well as those from earlier work, led Woods and Teuber to a tentative hypothesis which may have considerable generality in explaining the bewildering variety of early lesion effects in man: “The earlier the lesion, the greater the reorganization of neural mechanisms underlying behavior” (WOODS, personal communication). An alteration of neuronal connections after early lesions had been proposed by Kennard as an explanation of sparing of function, but the idea received little attention in the absence of histological evidence. Now, experimental neuroanatomical findings obtained over the last decade in experiments with animals have lent credence to this type of notion (though it may not help explain the original Kennard observations-see [26]). In work with Syrian hamsters, encouraged and supported by Teuber from its inception in the laboratory of W. J. H. Nauta at MIT, my co-workers and I have found a correlated reorganization of both brain connections and behavior after lesions in the visual system soon after birth. Our evidence reveals not only the types of “collateral sprouting” of axons and axonal endings which have been reported to follow certain lesions in mature animals ([27-311 reviewed in [32]). We also find a redirected growth of axonal pathways interrupted before their development is completed, and a spreading of axon terminal arbors over a larger-than-normal territory [23, 32-381. To illustrate these findings, I will review some effects of neonatal lesions of the midbrain tectum in hamsters; several of these effects have been confirmed in other mammals ([39-41]; SCHNEIDER, unpublished data on Turkish hamsters and Mongolian gerbils). Following this review, I will present findings, includin, 0 some new data, on the behavioral consequences of abnormal connections of the optic tract. These findings not only underscore the importance of a basic understanding of the phenomena of neuronal development and plasticity, but they also lead us to specific expectations about the consequences of prenatal, perinatal and early postnatal brain injury in human beings. Implications for human neurology and psychiatry will be considered after presentation of the findings with animals. EARLY Subjects

POSTNATAL LESIONS OF THE SUPERIOR COLLICULUS IN HAMSTERS : NEUROANATOMICAL STUDIES

and methods

The Syrian hamster (Mesocricefrrs auratus) is born on the 16th day after a successful mating. terminal projections of the optic tract have not yet formed, although some of the retinofugal

Most of the axons have

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already reached the superior colliculus [42, 431. (This stage is reached long before birth in the human; we estimate it to be about 2) months after conception.) Hamsters at birth can be subjected to surgical procedures carried out under mild hypothermia. The superior colliculus (SC) at this age is not yet covered by the cerebral hemispheres, and can be seen through the transparent, cartilagenous interparietal bone. It is possible to destroy the superficial layers of the SC, where the optic fibers normally terminate, by applying heat to the overlying skull surface [23, 351. Experienced hamster mothers usually accept the operated pups back in the nest, and rear them normally. We have carried out some of our subsequent neuroanatomical experiments on 6-week-old animals, but we have allowed them to reach full size, at 12 weeks, before beginning most of our behavioral or electrophysiological experiments. For tracing of axonal pathways, we have relied primarily upon the staining of degenerating fibers and terminals after retinal or other lesions, or eye removal, using modified Nauta techniques [44, 451. In recent work we have also used the autoradiographic technique of tracing pathways labelled by radioactive proteins, after eye injections of tritium labelled amino acids [46]. In our electrophysiological studies, we have recorded from single and multiple units with microelectrodes, using standard procedures adapted for hamsters and for the requirements of accurate mapping of receptive fields throughout the entire visual field [47].

REVIEW

AND

DISCUSSION

OF ANATOMICAL

FINDINGS

If the superficial layers of the SC are destroyed at birth or on day 1, 2 or 3, the axons of the optic tract not only grow into and terminate in the remaining tectal tissue, but they also develop anomalous connections along their route over the surface of the caudal diencephalon (Fig. 1).

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FIG. I. Left: lateral-view reconstruction of rostra1 brainstem of normal adult Syrian hamster. A group of optic-tract axons and their terminations are depicted schematically; the tectothalamic pathway is shown in a similar manner. Right: similar view of brainstem of adult hamster which had undergone destruction of the superficial layers of the superior colliculus on the day of birth. Abbreviations: IC, inferior colliculus; LGd, dorsal nucleus of the lateral geniculate body; LGv, ventral nucleus of the lateral geniculate body; LP, nucleus lateralis posterior; OCh, optic chiasm; PT, pretectal area; SC, superior colliculus. (From [32].)

They form an abnormally dense terminal projection to the outermost layer of the ventral nucleus of the lateral geniculate body (LGv). In addition, after passing over or through the dorsal nucleus of the lateral geniculate, where they have a normal-looking terminal field, they end densely in the posterior part of the lateral nucleus (LP). In a normal hamster, the optic tract has very few terminals in this structure. The abnormal projection to LP has been

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confirmed with electron-microscopic observations [34,48]. It is interesting to note that both of these regions of anomalous input from the retina, in LGv and LP, normally receive a projection from the superficial layers of the superior colliculus, a projection which is abolished by the early lesion [35] (Fig. 1). An abnormally dense projection is also found in the pretectal area, which not only loses a projection from SC after the early surgery, but generally suffers partial direct damage (Fig. 1). In some of the hamsters with tectal lesions inflicted on the day of birth, the brachium of the inferior colliculus (BIC) was also destroyed. This band of fibers carries auditory information from the inferior colliculus to the medial geniculate body (MGB) of the thalamus. The axons of the caudal edge of the optic tract normally pass over the MGB without terminating there. However, in the hamsters with complete destruction of the BIC in addition to the lesion of SC, we have consistently found evidence of a direct retina1 projection to this auditory-system structure [34,35]. Synapses of this projection, as well as the one to LP, have been charted with the aid of an electron microscope [34]. The location of the anomalous retinal projections in a hamster with a combined lesion of the SC and the BIC are charted on a reconstructed lateral view of the brainstem in Fig. 2.

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/

FIG. 2. Brainstem of hamster case 19-1, viewed from the right side, reconstructed from serial sections. The superficial layers of the right superior colliculus (SC) and the brachium of the inferior collicuius (IC) were destroyed at birth. Anomalous retinal projections, as seen in silver-stained sections, are indicated by dots: heavy dots, degeneration that reaches the optic tract at the surface; unfilled dots, deep-lying degeneration; fine dofs, degeneration in the SC, PT and in the dorsal and lateral nuclei of the accessory optic tract. Arrows indicate plane of sections used in electron-microscopy of LP and the medial geniculate nucleus (MG). Other abbreviations: HAB, habenula; ped, cerebral peduncle; others as in Fig. 1. Scale: 1 mm. (From [34].)

If the early tectal lesion is made unilaterally, the anomalous projections described above develop on the side of the brain corresponding to the lesion. However, there is an additional anomaly which has led to a series of further experiments: axons which have reached the area of early tectal damage from the opposite eye recross the tectal midline to end in the media1 third of the superficial gray layer of the intact colliculus [35]. When this happens, the terminals of the axons from the other eye, which would normally be expected to occupy this space, are excluded (Fig. 3).

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FIG. 3. Upper: dorsal view of rostra1 brainstem of normal adult hamster. The courses of the left and right optic tracts are indicated, with terminal areas depicted by open and filled circles, respectively. Lower left: similar view of brainstem of adult hamster which had undergone ablation of the superficial layers of the right superior colliculus on the day of birth. The right optic tract has developed abnormal connections. Lower right: similar view in a case with right colliculus lesion as in previous case, but the right eye was also removed at birth. For simplicity, the small ipsilateral projection of the retina is omitted. Abbreviations: DTN, dorsal terminal nucleus of the accessory optic system; others as in Figs. 1 and 2. (From [32].)

It appears as if the populations of retinofugal axons from the two eyes compete for exclusive occupancy of the available tectal terminal space. This suggestion was supported by the results of a further experiment: the normal innervation of the intact colliculus was eliminated by removal of the opposite eye at birth, in addition to the unilateral tectal lesion. In this case, with their competition removed, the recrossing axons from the intact eye spread over the whole colliculus, on the “wrong” side of the brain [35] (Fig. 3). These experiments yielded an additional finding which is important for assessing the factors which influence the patterns of anomalous axonal growth. When the recrossing axons were able to increase their area of termination in the superior colliculus, the volume of tissue in LP receiving a dense, abnormal optic tract innervation was found to be reduced. Thus, it appears that the growth into LP represents not simply an invasion of a denervated area by adjacent axons; it represents also a “compensatory sprouting” of axons unable to find their normal terminal space elsewhere. This led to the hypothesis that growing axons tend to conserve the total quantity of their terminal arbor; the effect on anomalous axonal growth was called the “pruning effect” because of its resemblance to compensatory growth in trees after pruning [35, 491. Further evidence for this hypothesis has been reported by DEVOR [50] in a study of early lesions of the lateral olfactory tract. He found evidence not only for compensatory sprouting of transected or blocked axons, but also for a compensatory

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stunting of olfactory tract axons which had sprouted supernumerary collaterals along their route, into a region of denervation (see Fig. 4). One may propose that many neurons are genetically programmed to form a specific number of synapses (see [jl]). The mechanism underlying this rule would have to involve a retrograde axonal flow of information from synpases to cell body.

FIG. 4. Diagrammatic representation of the proposed principle of conservation of total axonal arborization. The normal states are depicted at the left of each pair of diagrams. Sites of lesions are indicated by heavy lines. (A) Compensatory sprouting of cut fibers. @) Compensatorystunting of distal branches of the axon on the left (arrow) parallels growth of its more proximal branches into vacated terminal space above the lesion. (From [49].)

The phenomenon of recrossing retinotectal axons after unilateral lesions of the SC a birth in hamsters has also made possible a particularly clear demonstration of the role of age in the growth of anomalous projections [38]. The superficial layers of the right SC were ablated on the day of birth, and the right eye was removed at different ages in different hamsters. When the eye was removed between days 6 and 12, there was a progressive decrease in the quantity of the recrossing projection. If the eye removal was delayed until day 14 (the day when eye opening is just beginning), no obvious spreading of the recrossing axons could be detected. It is as if the terminals of the optic tract become fixed at the age of 2 weeks after a period of plasticity. In general, it appears that when neuroanatomical anomalies are associated with lesions inflicted before a “critical age”, this age can be different from one brain region to the next, even for the same species [35, 50, 52-541. This should not be surprising for phenomena dependent on redirected growth after damage to developing axons, considering the heterochronicity of developmental events. However, it should be kept in mind that in some systems, regenerative sprouting of transected axons, and collateral sprouting of partly damaged, or even intact, axons has been observed in adult animals (for reviews, see [32, 55-601). The above examples of altered retinal projections in animals which had suffered brain lesions in the neonatal period lay a sufficient groundwork for a consideration of functional effects on the whole organism. However, our ability to predict, and perhaps even in some measure to control, the development of such projections-in man as well as in other animals -will require an understanding of the growth rules acting at the level of single cells. It is these rules, distinct from any functional usefulness, which determine the quantity and pattern of the connections. Discussions of some of the possible cellular factors have appeared previously [32, 33, 35, 36, 38, 49, 50, 56, 61-641. These include the conservation rule, and the

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tendency for axons to invade adjacent denervated tissue, and “mechanical” factors involving growth along available surfaces. The topographic order in the representations of the retina found in optic tract terminal areas is, with little doubt, of great importance for normal function. Therefore, it is of interest to know the degree of topographic order found in areas of abnormal or reorganized retinal projections. At the cellular level, the order found makes clear the need to invoke additional axon ordering factors, which have long been a subject of intense interest among developmental neurobiologists [65-681. If the rostra1 or the caudal half of the superficial layers of the SC is removed in a newborn hamster, the entire retina forms an orderly projection to the remaining SC [36, 69, 701. The temporalmost part of the visual field is often not represented at the caudal tectal surface; instead, one finds successively more temporal parts of the field represented as one penetrates progressively below the surface of the SC [69]. In addition, one finds patches of totally aberrant topography, e.g. cells representing temporal field near the rostra1 border of SC [69, 701. When part of the superficial gray stratum (SGS) of the superior colliculus remains after the neonatal lesion, retinotopic order characterizes the retinal projection more than the signs of disorder. However, when the SGS is totally ablated, there is considerable disorder in the anomalous projection to the surface of the remaining deeper layers (see Fig. 3). Visual receptive fields of tectal cells in this region are abnormally large, and little retinotopic order is found [62]. The retinal projection to the wrong side of the midbrain in hamsters with early unilateral tectal lesions (Fig. 3) shows a fairly orderly, but subnormal, topography [62]. The axons recrossing the midline terminate in a pattern which is predominantly mirror-symmetric to the normal contralateral projection. Distortions in this pattern vary in degree. Small patches of retina may send their axons to multiple, separated patches of tectum. Local inversions of the mirror-symmetric topography sometimes occur, and there are distortions in the local “magnification factor”-the tectal area devoted to a given area in the visual field. Knowledge of the organization of the remaining retinotectal projection found in hamsters with neonatal tectal lesions, as reviewed above, helps explain some behavioral effects of these early lesions, described below.

FUNCTIONAL

IMPACT

OF ABNORMAL

RETINAL

PROJECTIONS

The optic tract of the Syrian hamster not only forms structurally normal-looking synapses in abnormal places after neonatal lesions of the superior colliculus [34, 48, 711, but these synapses are functionally active. The most direct evidence for this has been obtained with microelectrode recording in the damaged SC [62, 69, 721, in the intact SC on the wrong side of the midbrain after early unilateral tectal lesions [62], and in the nucleus lateralis posterior [72]. Our behavioral studies indicate the capacity for at least some of the anomalous connections to control visually elicited behavior. (1) Sparing of function

attributed

to anomalous connections

Turning of the head in response to visual presentation of food (sunflower seeds) appears to be permanently lost after sufficiently complete lesions of the SC in adult hamsters [23, 73, 741. Complete bilateral ablation of the superficial collicular layers in newborn hamsters, however, at least partially spares this ability [23]. Similarly, early unilateral lesions spare some of this orienting ability for stimuli presented in the affected visual field [32, 3.51. We have

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argued that this sparing of function is due to the anomalous retinal projection to the residual deep layers of the SC spared by the early ablation [23, 35, 361. The inability of the anomalous and the normal projections to the diencephalon (the two nuclei of the lateral geniculate body and the LP) to mediate the orienting movements independent of the retinal projection to the SC is supported by the results of recent experiments by SO [54]. He found that if the brachium of the superior colliculus was transected in hamster pups 4 days old, or older, the axons of the optic tract failed to grow past the lesion, but did form anomalous projections to LP and abnormally dense projections to the outer layer of the ventral nucleus of the LGB. However, the animals shelved no ability to orient toward visually presented seeds; directed turns occurred only when the vibrissae were touched. Thus, it appears that there is a true sparing of function that can be attributed to anomalous axonal connections, when lesions of the SC are inflicted sufficiently early in life in the hamster. Further data, on effects of a second tectal lesion in mature animals, increase the strength of this conclusion (see below). However, the spared orienting ability is not completely normal: a detailed analysis of the head movements of several hamsters with neonatal lesions of the SC has revealed various signs of an abnormal clumsiness, including overshooting of the goal, undershooting and abnormal slowness in reaching the target, and other signs of mismatch between sensory and motor systems ([32]; SCHNEIDER, AYRES and SINGER, unpublished, and see below). (2) Behavioral analysis of normal and abnormal turning by hamsters with unilateral tectal lesions at birth If the superficial layers of the superior colliculus on the right-hand side of the brain are ablated on the day of birth in a Syrian hamster, the left eye develops connections not only to the residual deeper layers of the right SC, but also, via an abnormal midbrain decussation, to the intact left SC (Fig. 3). With a visual stimulus presented in various parts of the visual field of the left eye, it is possible to elicit head turning not only in the normal, left-ward direction but also in the opposite, wrong direction [32, 351. Using videotape recording and subsequent slow- and stop-motion analysis, we have been able to obtain two kinds of data on this behavior. First, we are able to specify the positions of the stimulus, measured with respect to the head, from which turns in the correct or wrong directions can be elicited. Maps of the visual field, using the “food perimetry” technique described below, have been obtained for 15 hamsters with lesions of the right SC plus removal of the right eye at birth, and for 6 hamsters with only the early unilateral tectal lesion; similar maps have been obtained for 2 hamsters with one eye removed at birth, 4 hamsters with one eye removed in adulthood, and 5 normal animals. Second, we are able to plot the changing position of the head over time as it moves in response to a visual stimulus [32]. We have plotted such head movement trajectories, for stimuli presented at “eye level”, for a wide sampling of turning movements made by 5 normal hamsters, and for a more restricted sample of turns made by various animals with early lesions of the SC. Next, a description of the behavioral method is included. A more detailed report of these procedures is in preparation (Schneider and Ayres). Method. The apparatus consists of a round, Plexiglas platform glued to the top a plastic rod which holds it 28.5 cm above a table top. A hamster is placed on the platform and trained to wait relatively motionless with his nose close to a small raised hole, through which he is given sunflower seeds (Fig. 5a). When an animal will wait for at least 5 set without a

of

FIG. 5. Photos of hamsters on the “food perimetry”apparatus for testingvisuallyelicited turning towarda foodobject,asexplainedin the text.(a’)Hamsterwaiting for thestimulus toappear; stimulus hidden by baffle. (b) Hamster being rewarded, with a sunllo\ver seed, for a response. (c) Hamster at, or nearly at, end of a normal turning response. (d) Hamster ivith early lesion of right superior colliculus and right eye at end of a stimulus-elicited turn in the wrong direction. (Photos by John Urban.)

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reward, we begin to present the visual stimulus, a small black rubber ball (1.2 cm in diameter) which is slotted for holding a small seed, and mounted on the end of a stiff white wire which is held by hand. The stimulus appears against a white background, when it is moved from behind an opaque, white baffle which is 12-18 cm from the hamster’s head (Fig. 5a). Any turning response, regardless of its accuracy or direction, is rewarded by rapid presentation of a seed (Fig.Sb), which the hamster usually puts in a cheek pouch. Videotaping begins only after turning responses are occurring regularly. Pictures are obtained through an overhead camera (see Fig. 5c), and simultaneously through a side-view camera; our machine (Pana-. sonic NV-204 uses l-in. videotape, which we later analyse frame-by-frame on a 21-in. monitor screen. It should be mentioned that the hamsters generally ignore the white wire if the rubber ball is missing, though they will respond to the ball even if the sunflower seed is not attached. A one-eyed animal fails to respond when the stimulus is placed anywhere in the blind field, which assures us that non-visual cues play no significant role in eliciting the turning movements we are recording. To be included in our analysis, a turning response must meet several criteria. The movement must begin within 2 set of stimulus appearance. It is not used if the animal turns just before, or during, the initial presentation of the stimulus. If in a day’s session the animal is not exhibiting 5 set or longer delays at the hole, the entire session is not analysed, and the hamster is given an additional training session, with seeds presented only through the hole, on the following day. During testing sessions, we attempt to elicit an equal number of turns to both right and left sides, using stimulation of the vibrissae to elicit turns to the right when the eye on the right side is missing. Stimulus positions can be measured to an accuracy of about 5” in a polar coordinate system centered on a point midway between the eyes, with 0” being the straight-ahead position of the head before the response onset. Elevation at eye level is considered to be 0”. For plotting a head movement, the angle between the stimulus and a line extended straight forward through the center of the head, as seen by the overhead camera, was measured on every 5th frame, equivalent to every & set (83+ msec). Visualfield mapsjor correct- and wrong-direction turns. Figure 6 shows typical maps of the left visual field for two hamsters with removal of the superficial layers of the right SC at birth (both eyes left intact). Maps for animals with an additional removal of the right eye at birth have been published previously (35, 36, 75) and another appears in Fig. 8. In our testing situation, turns in the wrong direction have only very rarely been seen except in animals with early lesions that cause retinal projections to the wrong side of the midbrain. In the hamsters with such an anomalous re-crossing projection, wrong-direction turns occur predominantly in the upper temporal field of the head. If this position is determined with respect to the eyeball, it corresponds to the upper field as determined by eye muscle attachments. It is interesting to note that this area corresponds to the medial part of the SC in a normal hamster, where the recrossing retinal projections are most dense in the one-eyed animals with early unilateral tectal lesions, and where they are restricted in the two-eyed animals (Fig. 3). However, a few wrong direction turns occur in some animals for stimuli presented in the lower field of the eye (lower-nasal with respect to the head), as shown in Fig. 6. Although there are areas of the visual field where turns only in the correct or in the wrong direction are seen, there is usually a large area where turns in both directions are obtained. Some of this overlap may represent effects of eye movements, which are not measured or controlled. However, electrophysiological data indicate that there are retinal areas with projections to both sides of the midbrain [62].

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FIG. 6. Results of videotape analyses of the left visual field in hamster cases 44-7 (kfr) and 42-12 (right) in which the superficial layers of the right superior colliculus were ablated on the day of birth. The visual field is represented as the surface of a sphere, centered on the point midway between the eyes, with the nasal pole at the left. Grid lines are 20” apart with extra lines at horizontal eye level and at 90” from the straight ahead. Open circles represent positions of the stimulus where turns in the correct direction were elicited. Black squares represent stimulus positions where turns in the opposite (wrong) direction were evoked. Circles inside squares represent turns which included a reversal of direction (“ambivalent” turns). Dots represent a failure to respond.

Head-movement trajectories. Normal hamsters, after becoming accustomed to making orienting movements to obtain sunflower seeds in the apparatus, turn towards eye-level stimuli in an accurate and regular manner (Fig. 7a). The head turns rapidly at first, then more slowly until it is directly in line with the stimulus (_I 5’). The completion of a turn was signalled by the head’s reaching a position which it then maintained (to within 5”) for at least 3 sec. Normal animals typically completed their turning movements in about + set; this varied slightly from animal to animal. Although shorter turns were often completed in less time, this was not always the case since the initial speed was often lower for shorter turns. Some of the left-ward (correct direction) turns made by the hamsters with early lesions of the right SC were fairly normal in their trajectories. However, we have frequently observed very innacurate turns with trajectories not seen in the normal records, e.g. consistent overshooting for stimuli placed in the nasal part of the field [32] (also Fig. 7b). Several animals have shown turns that take an abnormally long time to complete, and are broken by frequent pauses (Fig. 7c) whereas other turns simply come to a halt far short of the goal (Fig. 7d). Such behavioral anomalies, like the turns in the wrong direction, can be interpreted as a consequence of a mismatch between the sensory map near the tectal surface, determined by the topography of the retinofugal afferents, and the “motor map”, determined by the organization of the deeper-lying tectal output neurons (cf. [76]). Thus, if a large part of the visual field is represented in the rostra1 end of the SC, which normally represents only the nasalmost field, one would expect that the turning movements elicited by the more temporal stimuli would initially be directed at points in the more nasal field, i.e. the animal would show undershooting, repeatedly until the goal was finally reached. By similar reasoning, overshooting would be predicted in cases where the nasal field is represented in more caudal parts of the tectum than normally.

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FIG. 7. Head-movement trajectories plotted for four adult hamsters from videotape records. Curves show movement in the horizontal plane in response to the small black stimulus that appeared at various positions, at eye level or up to 20” above eye level, in the left visual field. Ordinate: position of stimulus with respect to the straight-ahead position of the head, in degrees of arc. Abscissa: time from onset of response; a point was plotted for every l/12 set (every 5th frame on the videotape). (a) Three turns by normal hamster no. 2. (b) Four turns by normal no. 1. Normal turns can be considered ended when the head remains within 10” of one position for l/3 set, but they are extended further here for comparison purposes. (c) Two undershoots, ending above the zero line, and two overshoots ending below it. The solid lines represent turns by hamster 102-2, and the dashed lines are for case 102-l ; each of these animals had lesions of the right superior colliculus plus removal of the right eye on the day after birth. (d) Three slow or “hesitant” turns by the same two animals.

When the hamsters turn in the wrong direction, they generally fail to turn to positions which are mirror image to the position of the seed, whereas the retinal representation in the wrong colliculus shows a mirror-image polarity [69, 771. These data are compatible with the hypothesis that the hamster, unlike the frog in a similar situation [78], does not turn in a completely ballistic manner, but can modulate his movements on the basis of visual input obtained during the turn. This is supported by the fact that the hamsters’ turns take about three times as long as the frogs’ [77]. A hamster making a wrong-direction turn will usually halt his movement when it causes the stimulus to move beyond the edge of his visual field’ (SCHNEIDER and SINGER, unpublished data [32]). This use of visual feedback to modulate ongoing turning movements may vary from time to time and from animal to animal,

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suggesting that the sensory-motor mismatch in the SC, even if known in detail, is compatible with a considerable variability in head-turning trajectories. This fits our observations on hamsters with lesions of the SC at birth. (3) Abnormal behavior due to anomalous connections can be abolished by “corrective surgery” in adult animals In hamsters with ablations of both the right eye and the right SC at birth, many of the optic tract axons which recross the midline at the tectal surface are fasciculated, forming a large bundle of fibers which can readily be seen grossly if the midbrain surface is exposed in the mature animal (see Fig. 16 in [35]; also Fi g. 3 above). In two hamsters with this anomaly, we have first mapped the visual field for correct- and wrong-direction turns as described above, and then we have surgically transected the recrossing bundle through a small right occipital craniotomy, after aspiration of a small part of the overlying hemisphere. In one case (heretofore unpublished), the retinal projections were studied with the autoradiographic method after behavioral testing was complete. The histology revealed no midbrain damage except for an incomplete, but nevertheless considerable, transection of the abnormal decussation at the tectal midline. The anomalous projection to the damaged right SC was intact, whereas very few axons reached the medial SC on the left, where the recrossing projection is normally most dense. Sections stained for degenerating axons [44] showed a complementary picture of heavy anterograde degeneration of axons crossing the tectal midline in the anomalous bundle. Behaviorally, this animal showed a nearly total loss of wrong-direction turning after the adult surgery, while the field of correct-direction turning was intact (Fig. 8). In a second, earlier case, the adult surgery caused a much deeper midline lesion, with damage to the medial part of the residual right SC. After this operation, nearly all wrong-direction turning was abolished, whereas correct-direction turning gradually recovered except in the upper nasal field ( Figure in [75]).

b

FIG. 8. Maps of left visual field, plotted as in Fig. 6, I or case 98-6, with a lesion of the right superior colliculus and removal of the right eye on the day after birth. When this animal was 14 months old, most of the recrossing retinotectal fibers were transected at the tectal midline surface after a right occipital craniotomy. (a) Before the adult surgery; (b) data obtained after the adult surgery over a period of 2 months, beginning I month after operation. Dots outside right edge of hemisphere represent control stimulus presentations directly behind the animal.

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(4) Abnormal behavior attributable to anomalous connections can be “unmasked” by brain damage in adulthood Electrophysiological recording of unit activity in the left colliculus of hamsters with lesions of the right SC and right eye at birth has generally revealed an anomalous representation of a larger part of the visual field than would be predicted from the visual field maps of wrongdirection turning. This contrast has been verified in two animals which were recorded from after the behavioral mapping procedure had been completed [62]. The absence of wrongdirection turning in response to stimuli in the lower nasal field (lower field of the eye) indicates that activity in the recrossing retinofugal axons projecting to the lateral part of the left SC does not lead to a behavioral response, although it can lead to unit activity. This suggests that projections from the corresponding areas of the retina terminate on both sides of the brain, and the projection to the early damaged right side is dominant. To test this hypothesis, we have attempted to undercut the right SC after aspiration of overlying hemisphere tissue, using an incision through the lateral margin of the mesencephalon, attempting to avoid the optic tract axons coursing over the surface. Three case descriptions, previously unpublished, will be given. In one case with this second lesion of the right SC (Fig. 9), the initial postoperative behavior revealed a complete loss of correct-direction turning,’ while wrong-direction turning was retained. Some correct-direction turning gradually recovered, but this recovery was very incomplete. Most interesting was an expansion of the field from which wrong-direction turns could be elicited (Fig. IO). Some of these abnormal turns now occurred for stimuli in the lower nasal field, indicating an “unmasking” of the function of the corresponding retinal projections to the wrong side of the midbrain. A second case gave similar results except for a lack of a clear expansion of the field of wrong-direction turning. A third case revealed a different type of “unmasking” of anomalous function. In this animal, the undercutting in the adult animal was attempted with a caudal approach, avoiding damage to the hemispheres [23, 73, 741. Histology revealed that the lesion had undercut most of the medial 3 of the right SC; it had also transected some of the recrossing axons, and had undercut the medial half of the left SC (Fig. 11). Thus, only the lateralmost part of the retinal projection to the residual right SC was on cells for which a direct passage to deeper tissue was unobstructed. Behaviorally, this animal lost all wrong-direction, as well as correct-direction turning in the nasal and uppermost part of the visual field (Fig. 12a, b). In further testing, the animal was intentionally rewarded on the “wrong” side (the right-hand side): visual stimulus presentations on the left were followed by elicitation of right-ward turning by whisker stimulation. Although the field of correct-direction turns expanded slightly in final testing, no turns in the wrong direction could be elicited (Fig. 12~). However, it was noted that most of the turns in response to stimuli 20” or more above eye level had an abnormal downward component (Fig. 12c), in contrast to the preoperative behavior, in which the animal generally turned without a noticeable upward or downward component, regardless of stimulus position. This peculiarity would be expected if cells with input from the upper field were connected with the output of the lateral tectum, which normally gets input from the lower field. This condition probably occurred in the present case because of the sparing of the lateral SC by the adult undercut, and because of the abnormally diffuse organization of the retinal projections to the residual deep layers of the SC after a superficial lesion at birth [62]. If this type of organization occurred in this case, input from a large part of the visual field reached the part of the lateral tectum which had not been undercut.

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.,

:

.

IC

FIG. 9. Histological results for case 137-1, subjected to a lesion of the right superior colliculus (SC) and removal of the right eye on the day of birth, and an undercut of the residual right SC at age 18 months via a lateral approach after removal of overlying cortex. When the animal reached 23 months, 20 PCi each of tritiated leucine and proline were injected into the vitreous body of the left eye, and after 24 hr the animal was perfused and prepared for autoradiography. Left: Frontal section through center of intact left SC. Small dots represent optic-tract fiber and terminal labelling. The undercutting knife entered the lateral edge of the brainstem just caudal to this level. Righf: Dorsal-view reconstruction of rostra1 brainstem. Dotted outlines are from a normal brain, solid lines are reconstructed from this case. Solid horizontal bars: terminal labelling reaching the brain surface (in SC) or the optic tract (elsewhere); interrupted bars indicate reduced densities; open bars represent terminal labelling not reaching the surface (data plotted from every 5th section). Tissue overlying the vertical hatching was undercut. Double arrows indicate level of the section at the left. Scale marker, I mm. Abbreviations: CG, central gray; IC, inferior colliculus; MGB, medial geniculate body; LGd, dorsal nucleus of the lateral geniculate body; LP, nucleus lateralis posterior; PT, pretectal area; SGS, superficial gray stratum of SC; SN, substantia nigra.

N

:T

N

FIG. 10. Maps of left visual field for case 137-1, obtained before the adult undercutting surgery (a), or afterwards (b) over a period of 5 months beginning 1 week postoperatively. Plotted as in Figs. 6 and 8.

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FIG. 11. Histological results (prepared and displayed as in Fig. 9) for case 102-2, subjected to ablation of the superficial layers of the right SC and removal of the right eye on the day after birth, and a partial tectal undercut at age 19 months via a caudal approach (neocortex undamaged). Two-and-a-half months later the eye was injected, as for case 137-1, to label the optic tract axons. Lefr: Frontal section showing tectal undercut; just caudal to this level, the cut partially transected the fibers crossing the midline surface into the left SC. Dots represent optic tract fibers and terminals. Right: Dorsal-view reconstruction with data displayed as in Fig. 9. Short slanting lines represent labelled fibers of the recrossing bundle. Additional abbreviation: MTN, medial terminal nucleus of accessory optic tract.

(5) Abnormal behavior due to anomalous connections can be suppressed or enhanced by reward conditions (preliminary

report)

In the behavioral testing of hamsters with an anomalous retinal projection to the wrong side of the midbrain described above, animals were rewarded for turning responses regardless of their accuracy. If the reward conditions are varied, somewhat different results are obtained ([35] and SCHNEIDER and SADUN, unpublished data obtained without the benefit of videotape analysis). If turning in the wrong direction is never rewarded, this abnormal behavior is suppressed, but not replaced by normal function. In areas of the visual field where responses in both correct and incorrect directions are obtainable (see Fig. g), nonreward of either the correct- or the wrong-direction turning responses leads to their disappearance, while the rewarded type of response remains strong. Thus, for this sector of the visual field, it appears that the reward contingencies can determine whether the more normal or the more abnormal behavior will occur. When turns in the wrong direction have dropped out due to non-reward, they may reappear after a period of several days without visual stimulus presentations, and they can be easily reinstated if they are rewarded. They have also been observed to reappear, without reward, under conditions of arousal produced by extraneous novel auditory stimulation.

POSSIBLE

RELEVANCE

FOR OUR OWN SPECIES: AND SPECULATIONS

COMMENTS

The experimental work with animals we have reviewed and presented above shows the plausibility of the belief that the earlier the brain damage, the greater the likelihood of a reorganization of neuronal connections underlying behavior. This is essentially the hypothesis of Woods and Teuber, cited in the introduction, based on studies of early brain injury in man. The research with hamsters shows that redirected growth of axons after damage to their normal area of termination can cause striking behavioral anomalies as well

GERALD E. SCHNEIDER

FIG. 12. Maps of left visual field for case 102-2, plotted as in Figs. 6 and 8. (a) Before adult surgery. (b) After adult tectal surgery; testing during 27 day period beginning 2 weeks after operation. (c) Data from final 12 days of testing, after 1 month of training as explained in text. Filled circles: “correct-direction” turns with abnormal downward component.

as various degrees of functional sparing. These studies, and experiments with other mammals reported in the literature, have provided some clues to the rules of cellular growth which can enable us to make some predictions about neuroanatomical anomalies which may develop after specific types of early lesions. It is difficult to judge how common early brain damage, especially prenatal damage, in man may be since obvious behavioral signs of the type seen in cases of adult injury may not be found, because of functional sparing, except for the more massive lesions. Neuropathological study of brains could not easily uncover morphological signs of very early focal damage, since if lesions occur before a certain age they will not cause a glial scar* [35, 791; the only morphological trace may be a quantitative change in sizes of certain structures, *Scar formation can occur in human fetal telencephalon after 26-27 weeks of gestation, according to unpublished studies by F. Gilles and collaborators, Children’s Hospital, Boston.

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perhaps some alterations in cytoarchitectural details, and most importantly, some anomalies in axonal pathways and connections that would not be evident in the absence of experimental tracing methods. In the face of these difficulties, it may be helpful (and provocative) to use the experimental studies of animals to suggest some behavioral consequences of brain injury in man that is incurred sufficiently early to cause some reorganization of axonal connections. On the behavioral side, the work with animals has been concentrated on simple sensorimotor function, but the widespread neuroanatomical and correlated electrophysiological anomalies suggest that a much greater variety of behavioral consequences will be uncovered. Thus, one can expect alterations in sensory systems to affect sensory abilities. The finding that a topographic projection can be compressed or expanded into smaller or larger than normal areas after early lesions [33, 36, 69, 701 suggests that sensory acuity may be altered in a correlated manner; this speculation is based on the finding that the area of neocortex devoted to a given part of the visual field is specifically related to acuity [SO]. Thus, the reduced somatosensory acuity in the absence of focal signs seen in children with early cortical injury, as well as the less commonly observed enhancement of acuity [24], may find an explanation. A redirected growth of axons in motor systems could cause anomalous movements. Thus, the abnormal persistance and severity of mirror movements in childhood hemiplegia examined by WEEDS and TEUBER[25] may be due to an abnormally large uncrossed pyramidal tract. This possibility is suggested by the finding of an abnormal uncrossed corticospinal pathway in rats with early hemispherectomy [16, 81, 821. Abnormal connections may also result in a sparing of function, but an apparent sparing may be associated with misdirected movements or a clumsiness which is the motor equivalent of reduced acuity in sensory systems. Sensorimotor anomalies due to abnormal central connections in mammals have been well documented only for the hamster, as described above, but there is no reason to doubt that brain lesions at critical sites and times will lead to such anomalies in other species as well, including man. However, the modulations of such behavior produced by reinforcement contingencies (reward and non-reward) may be considerably more prominent in humans and other mammals with enlarged endbrainscf. the phenomenon of adaptation to peripheral nerve crossing, as studied in rats [83], cats [84] and monkeys [8.5]. It seems likely that axonal growth in the fimbic system follows rules similar to those operating in growth of sensory pathways after lesions (reviewed above). Redirected axonal growth in this system could result in an abnormal organization of emotional responsiveness and of autonomic nervous system control, as well as anomalies in cognitive control of these functions. Thus, it appears possible that some cases of psychosis may be a consequence of abnormal connections caused by early brain damage. Evidence pointing to an association between psychotic behavior (often diagnosed as schizophrenia) and early-specifically prenatal-temporal lobe tumors (hamartomas) has been assembled by FALCONER [86] and TAYLOR [87] from their studies of temporal lobe epileptic patients treated with unilateral temporal lobectomy. Although it appears that neuronal abnormalities attributable to frequently repeated ictal activity in temporal lobe structures can lead to psychotic symptoms [88], the Falconer and Taylor evidence raises the possibility of a separate factor, namely, anomalous growth of forebrain pathways after very early limbic system lesions. The majority of schizophrenic patients, however, are not temporal lobe epileptics, and there have been no consistent neuroanatomical anomalies demonstrated by examination of

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brains of such patients [89]. In the absence of quantitative studies that may be needed to detect prenatal damage, it is interesting to note findings of statistical studies which show a relationship bet\veen psychosis and complications of pregnancy and birth [90, 911, which suggest a higher incidence of prenatal and perinatal brain injury in patients with this affliction. Similar findings have been reported for infantile autism 1921. The nature of the anomalous axonal growth that may occur after early forebrain injury is suggested by the conditions which appear to promote the growth of altered connections after neonatal lesions in the hamster’s visual and olfactory systems ([32, 35, 49, 501 and revieued above). Axons Lvith branching in more than one structure may be more susceptible to anomalous growth than axons with more limited terminal distributions because a lesion affecting them is likely to destroy only part of their terminal field; the remaining axonal endings will promote the survival of the cells (by trophic influences that become most important after the initial period of axon elongation), while the loss of some branches will tend to cause a compensatory sprouting of the other branches (Fig. 4). These other branches will tend to invade adjacent areas which are denervated by the same (or another) lesion, although some areas may show such changes only if the lesion occurs before a critical age. Figure 13 illustrates some predicted changes in axonal connections after an early lesion in a hypothetical forebrain network. Two neurons (X and Y) with widely branching projections are depicted; two laminated structures (A, B) and two non-laminated structures (C, D) are outlined. The predicted changes produced by an early ablation of one of these structures(D) are illustrated in the second diagram; one axon (of Y) shows the major alterations, consisting of expanded distributions in A and C, compensating for a loss of its branches in D. Using this model (Fig. 13), we can suggest some possible consequences of prenatal injury to temporal lobe structures. Let structure D represent the amygdala and structures A and C the forebrain structures known to receive amygdala projections [93]. Neuron Y could be taken to represent a catecholamine-containing neuron, e.g. a noradrenalin-containing neuron of the locus coeruleus, believed to project widely to the forebrain [94, 951. The model suggests that injury to temporal lobe structures including the amygdala, if sufficiently early, will result in an enhanced distribution of catecholamine-containing axons in certain forebrain structures, e.g. those of the septal area. Such an alteration of anatomical pathways has been suggested by measures of noradrenalin content in limbic forebrain tissue of chronic paranoid schizophrenic patients [96]. lt is interesting to note that lesions of the hippocampus in ad~tlt rats have been reported to cause increased or altered projections of noradrenalincontaining axons to the septal area (3 1,97, 981. It is not known ivhether these changes would be greater if the lesions were inflicted very early in life. Earlier lesions may well cause different effects, including some anomalous growth of other axonal systems which normally project to the hippocampal formation. In the case of amygdala damage, similar possibilities must be considered. Dopamine-containing axons from the ventral tegmental area of the midbrain [95, 99, 1001 are especially suspect because of the currently popular hypothesis of dopamine anomalies in schizophrenia [lOl, 1021. The same model can be used to suggest some consequences of early lesions of neocortex. Such lesions in man appear to result in a general cognitive retardution which would not be expected from lesions incurred later in life, even though the specific sensory and motor symptoms of later lesions may be absent [ 19, 201. In Fig. 13, let neuron X represent a diffusely projecting neuron of the thalamus, suggested to exist in the ventromedial thalamic nucleus [103]; it could also represent a noradrenalin-containing neuron of the locus coeruhs

FIG. 13. Schematic representation of (top) normal axonal projections of neurons in three brain areas, and (MOW) some predicted effects of an early lesion in one or another of these areas. Changes predicted by coincidence of two factors: conservation of quantity of the terminal arbor (or synapse number), and invasion of adjacent vacated terminal space.

[94, 951. Let areas A and B represent neocortical association areas. An early lesion of one of these areas (B) could result in an expansion of non-specific axons in the other area, occupying terminal space vacated by the loss of the association connection (B to A; see Fig. 13, third drawing). As a consequence of this anomaly, the action of other association connections converging on the same area [104, lOS] could be reduced or even disrupted. Higher cortical functions dependent on association connections 1106, 1071 would suffer. Early lesions of neocortex may also lead to the formation of abnormal callosal connections, as reported for the rat by CUSICK and LUSD [IOS]. These may disrupt the normal functioning of cortical areas receiving such connections.

This paper b?gm %‘lth Hans-Lukas Teub?r‘s question: “15 it reaill; bcttz: to have your brain l&on early‘?” Esperimentj on the visual system of Syrian hamstsrs have indicated that the ansk\sr cannot be a simple yes or no, for it depends on the nature of changes in neuronal pathivays. and on the function one is cons&ring. Chanys in brain structures occur as a result of thz ~oorkinzs of d~~elopmzntai cellular mechanisms. irrespective of Lvhsther the result is functionally adaptive. The nature of the changes and their conssqusnces for behavior vary with ths jitz of thz &ion and Gth the age \vhen thi: damage is incurred. These consrqusnszs may be a functional sparing, nearly complete or wry partial, or they may be a functional retardation or tvf, P. and YULE, I\'. A A’ewopsyciriatric Study in Childhood. J. B. Lippincott, Philadelphia, 1970. TEUBER, H.-L. Recovery of function after brain injury in man. In O~conw of Severe Damage to the Central Nervous System, Ciba Foundation Symp., Vol. 34, pp. 159-l 86. Elsevier, Amsterdam, 1975. TELBER, H.-L. and RUDEL, R. G. Behavior after cerebral lesions in children and adults. Dev. Med. Child hlurol. 4, 3-20, 1962. TECBER, H.-L. The problem of plasticity lvith particular reference to the early development of brain and behavior. Working Paper, National Institute of .Iiental Health, USPHS, pp. I-55, 1972. TELBER, H.-L. Recovery of function after lesions of the central nervous system: history and prospects. .Veurosci. Rex. Prog. Bull. 12, 197-209, 1973. B.&cER, J. H. and HCGHES, K. R. Visual and non-visual behaviors of the rat after neonatal and adult posterior neocortical lesions. Physiol. Behav. 5, 427-441, 1970. GOLD\~AS,P. S. Functional development of the prefrontal cortex in early life and the problem of neuronal plasticity. E.rpl IVerlrol. 32, 366-387, 1971. GoLDus, P. S. An alternative to developmental plasticity: heterology of CXS structures in infants and adults. In Plasticity and Recovery ofFunction, D. G. STEIS, J. J. ROSENand N. BITTERS (Editors), PP. 149-I 74. Academic Press, h’ew York, 1974. GoLoxfks., P. S. Age, sex and experience as related to the neural basis of cognitive development. In Brain .Ilechani.wu in .Llentai Retardation, X, A. BLCHWALD and hl. A. B. BRAZIER(Editors), PP. 37% 392. Academic Press, New York, 1975.

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16. HICKS, S.

P. and D’AMATO,C. J. Motor-sensory and visual behavior after hemispherectomy in newborn and mature rats. ExpI Neural. 29,416-438, 1970. 17. MAHUT, H. and ZOLA, S. Ontogenetic time-table for the development of three functions in infant macaques and the effects of early hippocampal damage upon them. Nearosci. Absfr. 3,428, 1977. 18. NONNEMAN, A. J. and ISAACSON, R. L. Task dependent recovery after early brain damage. Behav. Biol. 8,

143-172.1973. 19. HEBB, D. 0. The effect of early and late brain injury upon test scores, and the nature of normal adult intelligence. Proc. Am. Phil. Sot. 85, 265-292, 1942. 20. HEBB,D. 0. The Orgunizafion ofBehavior. John Wiley, New York, 1949.

21. RUDEL, R. G. and TEUBER,H.-L. Spatial orientation in normal children and in children with early brain injury. Neuropsychologia 9, 401-407, 1971. 22. RUSSELL,W. R. Brain, Memory and Learning: A Neurologist’s View. Clarendon Press, Oxford, 1959. 23. SCHNEIDER,G. E. Mechanisms of functional recovery following lesions of visual cortex or superior colliculus in neonate and adult hamsters. Bruin Behav. Evol. 3, 295-323, 1970. 24. RUDEL, R. G., TEUBER,H.-L. and TWITCHELL,T. E. A note on hyperesthesia in children with early brain damage. Neuropsychologia 4, 35 I-356, 1966. 25. WOODS,B. T. and TELIBER,H.-L. Mirror movements after childhood hemiparesis. Neurology 28, 11521158, 1978. 26. DENNY-BROWN,D., YANAGISAWA,N. and KIRK, E. J. The localization of hemispheric mechanisms of visually directed reaching and grasping. In Cerebral Localization, K. J. ZULCH, 0. CREUTZFELDT and G.C. GALBRAITH(Editors). Springer, Berlin, 1975. 27. GOODMAN,D. C. and HOREL,J. A. Sprouting of optic tract projections in the brain stem of the rat. J. Comp. Nerrrol. 127, 71-88, 1966. 28. H~~MORI,J. Presynaptic-to-presynaptic

axon contacts under experimental conditions giving rise to rearrangement of synaptic structures. In Srucrare and Fancfion of Inhibitory Neuronal Mechanisms. U.S. VON EULER, S. SK~GLUSD and U. S~DERBERG(Editors), pp. 71-80. Pergamon Press, New York, 1968. 29. Ltu, C.-N. and CHAMBERS, W. W. Intraspinal sprouting of dorsal root axons. Arch. Near. Psychiat. 79, 4661, 1958. 30. MCCOIJCH, G. P., AUSTIN, G. M., LIU, C.-N. and Lrr;, C. Y. Sprouting as a cause of spasticity. 1. Neurophysiol. 21,205-216, 1958. 3 I. RAISMAN,G. Neuronal plasticity in the septal nuclei of the adult rat. Brain Res. 14,25-48, 1969. 32. SCHNEIDER,G. E. Growth of abnormal neural connections following focal brain lesions: constraining factors and functional effects. In Neurosurgical Treatmenf in Psychiatry, Pain and Epilepsy, W. H. SWEET, S. OBRADORand J. G. MARTIN-RODRIGUEZ(Editors), pp. 5-26, University Park Press, Baltimore,

1977. 33. 34. 35. 36.

37. 38. 39.

40.

41. 42. 43.

FROST, D. 0. and SCHNEIDER, G. E. Plasticity of retinofugal projections after partial lesions of the retina in newborn Syrian hamsters. J. Comp. Neuro/. 185, 517-568, 1979. KALIL, R. E. and SCHXEIDER, G. E. Abnormal synapticconnections oftheoptic tract in the thalamus after midbrain lesions in newborn hamsters. Brain Res. 100, 690-698, 1975. SCHNEIDER,G. E. Early lesions of superior colliculus: factors affecting the formation of abnormal retinal projections. Brain, Behav. Evoi. 8, 73-109, 1973. SCHNEIDER,G. E. and JHAVERI.S. R. Neuroanatomical correlates of spared or altered function after brain lesions in the newborn hamster. In Plasticity and Recovery of Function in the Central Nervous System, D. G. STEIN, J. J. ROSENand N. N. BUTTERS(Editors), pp. 65-109. Academic Press, New York, 1974. SCHNEIDER,G. E. and NAUTA,W. J. H. Formation of anomalous retinal projections after removal of the optic tectum in the neonate hamster. Ann!. Rec. 163, 258, 1969. So, K.-F. and SCHNEIDER,G. E. Abnormal recrossing retinotectal projections after early lesions in Syrian hamsters: age-related effects. Brain Res. 147, 277-295, 1978. BAISINGER, J., LUND, R. D. and MILLER,B. Aberrant retinothalamic projections resulting from unilateral tectal lesions made in fetal and neonatal rats. Expl Nertrol. 54, 369-382, 1977. CASAGRANDE, V. A., HALL, W. C. and DIAMOND,I. T. Formation of anomalous projections from the retina to the pulvinar following removal of the superior colliculus in neonatal tree shrews. Abstracts, Society for Neuroscience 2nd Annual Meeting, 1972. MILLER,B. F. and LUND, R. D. The pattern of retinotectal connections in albino rats can be modified by fetal surgery. Brain Res. 91, 119-125, 1975. FROST, D. O., So, K.-F. and SCHNEIDER,G. E. Postnatal development of retinal projections in Syrian hamsters: a study using autoradiographic and degeneration techniques. Neuroscience (in press), 1979. So, K.-F., SCHNEIDER,G. E. and FROST, D. 0. Normal development of the retinofugal projections in Syrian hamsters. Anaf. Rec. 187, 719, 1977.

580 44

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IS IT REALLY

BETTER

TO HAVE

YOUR

BRAIN

LESION

EARLY?

Zusammenfassunp

Aberrierendes Wachstum des Tractus opticus bei Hamstern in Folge von Lisionen des Tectum opticum zur Zeit der Geburt resultieren in einer Anomalie der retinalen Projektionen, die mit spezifischen Reaktionen korreliert sind. Unter diesen zeigen sich visuell ausgel8ste Drehreaktionen, die nach veroleichbaren Lisionen im Erwachsenenalter verloren qehen. Manchmal konnnt es jedoch zu "overshoot-" oder "undershoot-" Reaktionen,-und zum Teil Im Falle von frlhen unilateralen Lasionen erfolgen die Reaktionen langsam. oroiiziert der Tractus ooticus zur falschen Seite des Tectum opticum, was fbr_Stimuli in bestimmter Position imGesichtsfeld zu Drehreaktionen in die falsche Richtung flihrt. Diese fehlgesteuerten Bewegungen kinnen durch Belohnung verstarkt, durch Nichtbelohnung unterdrtickt, oder durch Sektion der anomalen Bahn beim erwachsenen Tier ausgelgscht nerden. Die von Tierversuchen abgeleiteten Grundsstze erlauben die Voraussage, dass spezifische Llsionen im menschlichen Ftjtus und in Neugeborenen ein spezifisches Muster alterierten Wachstums der neuroanatomischen Bahnen verursachen. Man darf annehmen, dass diese Ver8nderunqen Verhaltensanonalien verursachen, und zwar nicht nur der sensomotorischen,-sondern such der kognitiven Funktionen, der emotionellen Reaktionen und des emotionellen Ausdrucks. Einige neuropsychologische Untersuchungsergebnisse lassen sich in diesem Rahmen interpretieren. (Titel:

1st es wirklich besser, dass man seine Hirnverletzung Eine Revision des Kennard-Prinzips)

fr6h hat?