Neuronal plasticity: historical roots and evolution of meaning.

In this paper, we outline some important milestones in the history of the term "plasticity" in reference to the nervous system. Credit is given to William James for first adopting the term to denote changes in nervous paths associated with the establishment of habits; to Eugenio Tanzi for first identifying the articulations between neurons, not yet called synapses, as possible sites of neural plasticity; to Ernesto Lugaro for first linking neural plasticity with synaptic plasticity; and to Cajal for complementing Tanzi's hypothesis with his own hypothesis of plasticity as the result of the formation of new connections between cortical neurons. Cajal's early use of the word plasticity is demonstrated, and his subsequent avoidance of the term is tentatively accounted for by the fact that other authors extended it to mean neuronal reactions partly pathological and no doubt quite different from those putatively associated with normal learning. Evidence is furnished that in the first two decades of the twentieth century the theory was generally accepted that learning is based on a reduced resistance at exercized synapses, and that neural processes become associated by coactivation. Subsequently the theory fell in disgrace when Lashley's ideas about mass action and functional equipotentiality of the cortex tended to outmode models of the brain based on orthodox neural circuitry. The synaptic plasticity theory of learning was rehabilitated in the late 1940s when Konorski and particularly Hebb argued successfully that there was no better alternative way to think about the modifiability of the brain by experience and practice. Hebb's influential hypothesis about the mechanism of adult learning contained elements strikingly similar to the early speculations of James, Tanzi and Cajal, but Hebb did not acknowledge specifically these roots of his thinking about the brain, though he was fully aware that he had resurrected old ideas wrongly neglected for a long time. Lately the concept of neural plasticity has been complicated by attributing considerably different meanings to it. A scholarly paper by Paillard is used to show how an analysis in depth can clarify some confusion engendered by an unrestricted use of the concept and term of neural plasticity.

Behavioural and electrophysiological analysis of strabismus in cats: modern context.

We studied the effects of paralytic strabismus on visual behaviour and binocularity of cortical visual mechanisms by immobilization of one eye in adult cats. Visual discrimination abilities of the immobilized eye were significantly diminished despite extensive training with one or both eyes. The deficits are not caused by the immobilization itself but appear to reflect an adaptive mechanism to deal with double vision. The deficits with the immobilized eye persisted even after section of the optic chiasm, which effectively removes the direct cortical competition of the two eyes. Single-cell electrophysiological recordings showed that cortical cellular responses are modified by the immobilization, with loss of binocularity in some cells and shifting of receptive fields of other cells that continued to respond to both eyes.

The contribution of general and specific motor inhibitory sets to the so-called auditory inhibition of return.

The detection of sounds that come from a region of space recently exposed to acoustic stimulation is often slower than the detection of sounds coming from regions of space previously unexposed to acoustic stimulation. The relative increase in reaction time (RT) to targets in recently stimulated locations is generally termed "inhibition of return" (IOR). This term alludes to the possibility that spatial attention is biased against returning to recently visited locations, thus favoring the sampling of new sources of information. However, auditory IOR effects found in paradigms where subjects have to detect a first sound (cue) without making an overt response to it, and then respond as fast as possible to a second sound (target), may be due to a purely motor inhibition carried over from cue to target. Such motor inhibition has been shown to be maximal when cue and target belong to the same category, such as when they occupy the same spatial position. We have assessed the possible contribution of this motor inhibition to auditory IOR effects by having subjects respond to both cues and targets randomly presented in a right location and a left location. Reaction time to targets preceded by cues at the same location was longer than reaction times to targets preceded by cues at the opposite location (IOR effect). Compared to a condition in which subjects responded only to targets, the IOR effect was smaller, but still significant, in the double response condition, suggesting that such an effect depends on both motor inhibition and other factors, possibly related to covert spatial orienting and oculomotor control. A second experiment indicated that the IOR effect component independent of motor inhibition was slightly but significantly greater when space was relevant to the task because subjects had to report the positions of both cues and targets, compared to when space was irrelevant to the task because subjects were not required to report stimulus positions.

Taste laterality in the split brain.

Two patients with corpus callosum resection, one complete and the other sparing the genu and the rostrum, were tested for discrimination of three basic taste stimuli (sour, bitter, salty) applied to the right or left sides of the tongue. Responses were made by pointing with either hand to written words or images of visual objects corresponding to the stimuli, a language-based discrimination. In both patients, response accuracy was significantly above chance for both hemitongues but there was a significant advantage for the left side. Reaction time was shorter for left stimuli than for right stimuli but the difference was not significant. Eight normal controls matched for age with the patients performed equally well with right and left hemitongue stimuli and so did a third callosotomy patient with sparing of the posterior callosum, including the splenium. Tactile and visual tests showed that the left hemisphere was responsible for language-based responses in the first two patients. The results confirm and extend previous findings in another callosotomy patient, indicating that: (i) taste information from either side of the tongue can reach the left hemisphere in the absence of the corpus callosum; (ii) the ipsilateral input from the tongue to the left hemisphere is more potent functionally than the contralateral input and (iii) in the normal brain, the corpus callosum, specifically its posterior part including the splenium, appears to equalize the effects of the ipsilateral and contralateral gustatory inputs on the left hemisphere. Taken together with evidence about lateralized taste deficits following unilateral cortical lesions, the results also suggest that the gustatory pathways from tongue to cortex are bilaterally-distributed with an ipsilateral predominance that may be subject to individual variations.

Volitional covert orienting to a peripheral cue does not suppress cue-induced inhibition of return.

Detection reaction time (RT) at an extrafoveal location can be increased by noninformative precues presented at that location or ipsilaterally to it. This cue-induced inhibition is called inhibition of return or ipsilateral inhibition. We measured detection RT to simple light targets at extrafoveal locations that could be designated for covert orienting by local or distant cues. We found that cue-induced inhibition cooccurred in an additive fashion with the direct effects of covert orienting, i.e., it detracted from facilitation at attended locations and increased the disadvantage for unattended locations. Thus, cue-induced inhibition cannot be suppressed by a volitional covert orienting to the cued location; the co-occurrence of different facilitatory and inhibitory effects confirms the simultaneous operation of multiple independent attentional mechanisms during covert orienting.

Incomplete gustatory lateralization as shown by analysis of taste discrimination after callosotomy.

The lateral organization of the gustatory pathway in man is incompletely understood. Majority of the studies support an uncrossed projection from each side of the tongue to the cortex, but reports of an opposite crossed organization continue to appear in the neurological literature. We studied the lateral organization of the gustatory pathway in normal controls, a man with a complete callosal agenesis, and a man with a complete section of the corpus callosum, a right anterior-frontal lesion, and language in the left hemisphere. Sapid solutions were applied to one or the other side of the tongue, and subjects reported the taste of the stimulus either verbally or by manually pointing to the name of the taste. There were no differences in accuracy and reaction time between the right and left hemitongues of the controls and the genetically acallosal observer. By contrast, the callosotomy subject showed a constant marked advantage of the left hemitongue over the right for both accuracy and speed of response, though performance with right stimuli was clearly above chance. The left advantage can be attributed to the left hemisphere being favored by the essentially verbal nature of the task, or to the presence of a lesion in cortical gustatory areas in the right hemisphere, or to both factors. Whichever of these hypotheses turns out to be correct, the results unequivocally reject the notion of an exclusively crossed organization of the gustatory pathway from the tongue to the cortex, and favor the notion of a bilaterally distributed organization of this pathway with a marked predominance of the uncrossed over the crossed component.

Unconscious letter discrimination is enhanced by association with conscious color perception in visual form agnosia.

Adaptive behavior guided by unconscious visual cues occurs in patients with various kinds of brain damage as well as in normal observers, all of whom can process visual information of which they are fully unaware [1] [2] [3] [4] [5] [6] [7] [8]. Little is known on the possibility that unconscious vision is influenced by visual cues that have access to consciousness [9]. Here we report a 'blind' letter discrimination induced through a semantic interaction with conscious color processing in a patient who is agnosic for visual shapes, but has normal color vision and visual imagery. In seeing the initial letters of color names printed in different colors, it is normally easier to name the print color when it is congruent with the initial letter of the color name than when it is not [10]. The patient could discriminate the initial letters of the words 'red' and 'green' printed in the corresponding colors significantly above chance but without any conscious accompaniment, whereas he performed at chance with the reverse color-letter mapping as well as in standard tests of letter reading. We suggest that the consciously perceived colors activated a representation of the corresponding word names and their component letters, which in turn brought out a partially successful, unconscious processing of visual inputs corresponding to the activated letter representations.

The neurological basis of conscious color perception in a blind patient.

We have studied patient PB, who, after an electric shock that led to vascular insufficiency, became virtually blind, although he retained a capacity to see colors consciously. For our psychophysical studies, we used a simplified version of the Land experiments [Land, E. (1974) Proc. R. Inst. G. B. 47, 23-58] to learn whether color constancy mechanisms are intact in him, which amounts to learning whether he can assign a constant color to a surface in spite of changes in the precise wavelength composition of the light reflected from that surface. We supplemented our psychophysical studies with imaging ones, using functional magnetic resonance, to learn something about the location of areas that are active in his brain when he perceives colors. The psychophysical results suggested that color constancy mechanisms are severely defective in PB and that his color vision is wavelength-based. The imaging results showed that, when he viewed and recognized colors, significant increases in activity were restricted mainly to V1-V2. We conclude that a partly defective color system operating on its own in a severely damaged brain is able to mediate a conscious experience of color in the virtually total absence of other visual abilities.

Possible recoding of visual space in covert orienting tasks.

Reaction time to lateralized light targets is longer if targets are preceded by light stimuli in the same visual hemifield compared to when they are preceded by light stimuli in the opposite visual hemifield. The effect is probably caused by interactions between implicit oculomotor tendencies and covert shifts of attention. We show here that a similar, but much smaller, ipsilateral RT inhibition can be observed when all stimuli are presented in a display completely lateralized to one hemifield, where ipsilateral and contralateral are defined with respect to the midpoint of the display. The persistence of ipsilateral inhibition with unilateral stimulus displays can be accounted for by a recoding of visual space predicated on the centering of covert attention on the display midpoint rather than on the fixation point. The recoding seems to affect the control of covert attention and perhaps oculomotor control as well.

Some aspects of the history of the law of dynamic polarization of the neuron. From William James to Sherrington, from Cajal and van Gehuchten to Golgi.

William James was the first to suggest that propagation of impulses in the nervous system proceeds in one direction, from sensory to motor neurons, but not viceversa. His law of forward direction preceded the formulation of the law of dynamic polarization of van Gehuchten and Cajal, which assumed that nerve impulses are conducted cellulipetally along dendrites and cellulifugally along axons, based on different anatomo-functional properties of these neuronal components. Golgi did not accept the law of dynamic polarization because he believed that dendrites are involved in the nutrition of the neuron rather than in impulse propagation, and that impulses can travel in any direction in the axonal components of the diffuse nerve network. Sherrington in turn experimentally demonstrated that intraneuronic conduction is reversible, whereas, in accord with James's law, propagation of impulses along neuronal chains is irreversible, due to the valve-like action of synapses. The story of the law of dynamic polarization shows that neither Golgi nor Cajal paid much heed to Sherrington's findings and to neurophysiological studies in general, probably because they felt that histology alone could provide the key for understanding the general functioning of the nervous system. It is argued here that this attitude was detrimental to the progress of the neurosciences, because a multidisciplinary approach based on different techniques is inevitably called for in order to develop a plausible theory of the nervous system.

Paradoxically greater interhemispheric transfer deficits in partial than complete callosal agenesis.

Symptoms of interhemispheric disconnection are typically much less severe in callosal agenesis than after surgical section of the corpus callosum. Sperry [Sperry, R. W., Plasticity of neural maturation. Developmental Biology, 1968, 2 (Suppl.), 306-327.] has attributed this difference to two interconnected factors: (1) the callosal section is usually performed after the brain has lost the maximal degree of functional plasticity associated with the early stages of development and (2) the removal of an already formed structure is more disruptive for functional brain organization than the failure of the same structure to develop. It has been suggested that functional compensation is less efficient if callosal agenesis is partial rather than complete [Dennis, M., Impaired sensory and motor differentiation with corpus callosum agenesis: A lack of callosal inhibition during ontogeny? Neuropsychologia, 1976, 14, 455-469.]. This suggestion is supported by the present findings of partial left-hand anomia, partial left-field alexia and poor tactile cross-localization in a subject with a congenital absence of the posterior part of the corpus callosum due to an arteriovenous malformation. In agreement with many previous studies, similar, though more severe, symptoms of interhemispheric disconnection were found in a subject with a complete section of the corpus callosum, but not in a subject with complete callosal agenesis. Praxic control of the left hand on verbal commands was severely deficient in the callosotomy subject, but it was normal in the subject with callosal hypogenesis. The lesser degree of compensation in partial compared to complete callosal agenesis may be explained by a reduced pressure to develop extracallosal means of interhemispheric communication, contingent on the partial existence of callosal connections, as well as by the later occurrence in development of the causes of callosal hypogenesis compared to those of total callosal agenesis.

Rightward attentional bias and left hemisphere dominance in a cue-target light detection task in a callosotomy patient.

Six normal subjects and a callosotomized man with a prefrontal lesion, mostly on the right side, were tested in a reaction time (RT) task involving a key-pressing response to an extrafoveal light target preceded by an extrafoveal light cue. Cues and targets were presented along the horizontal meridian at 4 degrees and 12 degrees on the right and left of fixation. Fixation was maintained throughout each trial. The cue signalled the occurrence of the target within a time window extending from 200 to 4000 misec from the cue, but did not predict target location. Normal controls responded faster to medial than to lateral targets in both fields, but showed no between-field difference, and their RT was not affected by cue location. Furthermore, they showed the so-called 'ipsilateral inhibition' or 'inhibition of return' effect, their RT being longer when cues and targets occurred in the same field than when they occurred in opposite fields. The RT of the callosotomized subject showed a left-right gradient for both cue location and target location, being longest for the leftmost location and shortest for the right locations. In addition, he showed a significant advantage for the right hand regardless of cue and target location, as well as a consistent ipsilateral inhibition in the left field, whereas in the right field there was ipsilateral inhibition only at the two longest stimulus onset asynchronies. These results suggest that, at least under these experimental conditions, there was a rightward orientational bias which reflected the taking over of the control of performance by the left hemisphere. This attentional bias was reminiscent of that seen in patients with hemi-inattention from right hemisphere damage, although the callosotomized patient showed no sign of such hemi-inattention in routine clinical tests. On the basis of several considerations the rightward bias could be attributed to the callosal interhemispheric disconnection rather than to the right prefrontal lesion.

One or many arousal systems? Reflections on some of Giuseppe Moruzzi's foresights and insights about the intrinsic regulation of brain activity.

Soon after the birth of the hypothesis of the ascending brainstem activating system, Giuseppe Moruzzi considered the possibility that a fractionated and differentiated arousing action of the reticular formation is required for effective behavior and cognition. Current knowledge about the chemically tagged brainstem systems which project diffusely to thalamus, neocortex and limbic structures has justified the assumption of the existence of multiple arousal systems. Combined changes in the activities of these systems are responsible for the sleep-wake cycle and the modulation of the reactivity of the brain to environmental inputs. There remains the physiological problem--one which has always been foremost in Moruzzi's thinking about the intrinsic regulation of brain activity--of how the separate actions of the different arousal systems are brought together into a functional whole. This problem still awaits experimental answers.

Spatio-temporal properties of the pattern of evoked phantom sensations in a left index amputee patient.

In a left index finger amputee, appropriate stimulation of skin areas of the remnant left fingers or left lower face evoked veridical sensations as well as sensations localized to the phantom finger. Five months after the amputation, there was a systematic correspondence between positions of digital and facial stimuli and positions of stimuli felt on the phantom. More than 3 years after the amputation, orderly maps of the phantom index on the ipsilateral fingers were still detected. By contrast, poorly organized facial maps were present only contralaterally to the amputation. The maps on the remnant fingers are likely to acquire stability because they are systematically activated during manipulations performed with the mutilated hand. The disorganization of facial maps may be related to their irrelevance for behavioral control in everyday life conditions.

The body in the brain: neural bases of corporeal awareness.

Recent studies have begun to unravel the brain mechanisms that underlie the mental representation of the body. Imitation of movements by neonates suggests an implicit knowledge of the body structure that antedates the adult body schema. This can include inanimate objects that bear systematic relations to the body, as shown by the elimination from self awareness of a body part and its associated paraphernalia after selective brain lesions. Dynamic aspects of the body schema are revealed by spontaneous sensations from a lost body part as well as by orderly phantom sensations elicited by stimulation of body areas away from the amputation line and even by visual stimulation. The mechanisms of the body schema exhibit stability, since some brain regions seem permanently committed to representing the corresponding body parts in conscious awareness, and plasticity, since brain regions deprived of their natural inputs from a body part become reactive to inputs from other body parts.

Disownership of left hand and objects related to it in a patient with right brain damage.

We describe a woman with right brain damage who denied the ownership of her left hand and of extracorporeal objects (e.g. rings) which were worn on the left hand itself. When the same objects were worn on the right hand or were held by the examiner, the patient correctly recognized them as her own. Other personal objects unrelated to the left hand (e.g. pins, earrings, comb) were always correctly recognized as her own. Thus, by inference, the mental image of one's body may include inanimate objects which had been in contact or in close proximity with the body itself. These findings provide, for the first time, experimental support to the speculative notion of an extended body schema.

Spatial stimulus-response compatibility in callosotomy patients and subjects with callosal agenesis.

Subjects with partial or complete defects of the corpus callosum, either congenital or acquired, performed a choice reaction time (RT) task involving a right or left key-press response to a light presented at random in the right or left hemifield. Like normal subjects, all of them exhibited two additive effects typical of these tasks: the spatial stimulus-response compatibility effect (faster RT for stimuli and responses matched for side), and the hand placement effect (longer RT for responses performed with crossed hands). Two subjects with a complete callosal defect, one acquired and the other congenital, showed a third effect, not present in normal subjects, consisting of a marked advantage for RT of responses with hand anatomically ipsilateral to the stimulus, independent of both stimulus-response compatibility and hand placement. These findings can be interpreted according to a hierarchical model of information processing assuming that, in the absence of the corpus callosum, the matching of the mental codes for the stimulus and response sets takes place solely in the hemisphere receiving the stimulus, with a subsequent rapid-intrahemispheric or slow-interhemispheric transmission of the response command to the appropriate motor centers.