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Self-perception and action in infancy.

By 2-3 months, infants engage in exploration of their own body as it moves and acts in the environment. They babble and touch their own body, attracted and actively involved in investigating the rich intermodal redundancies, temporal contingencies, and spatial congruence of self-perception. Recent research is presented, which investigates the spatial and temporal determinants of self-perception and action infancy. This research shows that, in the course of the first weeks of life, infants develop an ability to detect intermodal invariants and regularities in their sensorimotor experience, which specify themselves as separate entities agent in the environment. Recent observations on the detection of intermodal invariants regarding self-produced leg movements and auditory feedback of sucking by young infants are reported. These observations demonstrate that, early in development and long before mirror self-recognition, infants develop a perceptual ability to specify themselves. It is tentatively proposed that young infants' propensity to engage in self-perception and systematic exploration of the perceptual consequences of their own action plays an important role in the intermodal calibration of the body and is probably at the origin of an early sense of self: the ecological self.

Body Image↗

Infant lesion effect: III. Anatomical correlates of sparing and recovery of function after spinal cord damage in newborn and adult cats.

We have demonstrated that sparing of tactile placing occurs after neonatal but not adult spinal cord damage and that the spared tactile placing of one limb depends on the corresponding (contralateral) sensorimotor cortex. In order to determine whether anatomical reorganization of the corticospinal or brainstem-spinal pathways also occurred which might account for the sparing of the tactile placing response, we used retrograde transport of horseradish peroxidase to map supraspinal neurons which project caudal to a spinal hemisection made either neonatally or in adulthood. The pattern of HRP labeling in the brainstem was identical in both the neonatal and adult operates. Neonatal operates, however, showed severe retrograde cell loss in brainstem nuclei which projected to the damaged side of the cord. This massive retrograde cell loss was not seen when lesions were made in the adult. In contrast, sparing of corticospinal projections and anatomical reorganization of the corticospinal tract were found after neonatal, but not adult spinal cord lesions. In adult operates, this lesion abolished HRP labeling in the contralateral sensorimotor cortex, while in all of the neonatal operates, HRP labeled cells were found throughout these cortical areas. The labeled cells had many characteristics in common with those of the normal CST. They were located in lamina V of cytoarchitectonic areas 4, 3, 1-2, and 5. Although the range of cell diameter was normal, the mean diameter of these spared neurons was below normal. Although the 'spared' CST may share many characteristics with the normal CST, its axons must have reached caudal segments of the cord by an abnormal pathway, since the normal route for the CST was destroyed by the lesion. The results indicate that two different regions of the CNS responded differently to the same neonatal lesion. Growing CST axons exhibited anatomical plasticity, contrasting with the retrograde death of the brainstem spinal tracts. We suggest that this difference between the two classes of pathways is due to the difference in time of their development. Only the latest developing pathways displayed anatomical sparing. The difference may also be seen in terms of the behavioral results. Only late-developing motor patterns were spared after neonatal lesions.

Age Factors↗

Prediction precedes control in motor learning.

Skilled motor behavior relies on the brain learning both to control the body and predict the consequences of this control. Prediction turns motor commands into expected sensory consequences, whereas control turns desired consequences into motor commands. To capture this symmetry, the neural processes underlying prediction and control are termed the forward and inverse internal models, respectively. Here, we investigate how these two fundamental processes are related during motor learning. We used an object manipulation task in which subjects learned to move a hand-held object with novel dynamic properties along a prescribed path. We independently and simultaneously measured subjects' ability to control their actions and to predict their consequences. We found different time courses for predictor and controller learning, with prediction being learned far more rapidly than control. In early stages of manipulating the object, subjects could predict the consequences of their actions, as measured by the grip force they used to grasp the object, but could not generate appropriate actions for control, as measured by their hand trajectory. As predicted by several recent theoretical models of sensorimotor control, our results indicate that people can learn to predict the consequences of their actions before they can learn to control their actions.

Biophysical Phenomena↗

Kindling of basolateral amygdala but not ventral hippocampus or perirhinal cortex disrupts sensorimotor gating in rats.

The neural mechanisms mediating prepulse inhibition (PPI) appear to have relevance to neurological and psychiatric disorders. Patients with temporal lobe epilepsy exhibit psychotic symptoms and disrupted PPI, therefore the present experiments examined the consequences of seizures induced by kindling on PPI. Rats were chronically implanted with an electrode into the basolateral amygdala, perirhinal cortex, or ventral hippocampus and stimulated twice daily until 3 fully generalized, class 5 seizures were elicited. Kindling of basolateral amygdala, but not perirhinal cortex or ventral hippocampus, disrupted PPI when testing began 2min, but not 48h, following the elicitation of the third class 5 seizure. Startle amplitudes were unaffected by kindling. These results suggest that the anatomical origin of seizures is an important factor in determining their potentially disruptive effects on PPI.

Amygdala↗

Development of oral-motor skills in the neurologically impaired child receiving non-oral feedings.

Treatment of children with swallowing dysfunction requires a holistic approach based on a global view of their problems and needs. The connection of the swallowing mechanism with the sensorimotor organization of postural tone and movement throughout the body is a critical factor in the evaluation and treatment of children whose dysphagia is rooted in a neurologic disorder. An appropriate program includes work with the development of movement skills, sensory processing, learning, social skills, and communication. The initial focus is placed on oral-motor treatment, rather than direct work on oral feeding. The primary goal of the program is to develop the appropriate use of the mouth, respiratory, and phonatory systems in exploration, sound play, and as much oral feeding as possible. Oral feeding is the by-product of a total program, not its major goal.

Child↗

Grafts of embryonic substantia nigra reinnervating the ventrolateral striatum ameliorate sensorimotor impairments and akinesia in rats with 6-OHDA lesions of the nigrostriatal pathway.

Previous studies have shown that transplants of embryonic substantia nigra, which reinnervate the dorsal neostriatum, can compensate for certain, but not all, behavioural deficits induced by unilateral or bilateral destruction of the nigrostriatal dopamine pathways in adult rats. The present study shows the nigral transplants which are placed in the lateral cortex so as to reinnervate ventral and lateral parts of the neostriatum, give an entirely different pattern of behavioural recovery. Thus, the laterally placed grafts were more efficient than the previous dorsally placed ones in compensating for the sensorimotor asymmetry in unilaterally lesioned animals, and the akinesia seen after bilateral lesions. Conversely, the drug-induced motor asymmetry which was completely abolished by the dorsal grafts was not significantly affected in the present animals. These results support the idea of topographic heterogeneity with respect to striatal functions, and suggest that the technique can be used as a tool for more detailed analysis of the functional organization of the meso-telencephalic dopamine systems and the functional heterogeneity of the dopaminergically innervated striatal-based forebrain regions.

Animals↗

Chronic [D-Ala2]-growth hormone-releasing hormone administration attenuates age-related deficits in spatial memory.

The age-related decline in growth hormone is one of the most robust endocrine markers of biological aging and has been hypothesized to contribute to the physiological deficits observed in aged animals. However, there have been few studies of the impact of this hormonal decline on brain aging. In this study, the effect of long-term subcutaneous administration of [D-Ala2]-growth hormone-releasing hormone (GHRH) on one measure of brain function, memory, was investigated. Animals were injected daily with 2.3 microg of [D-Ala2]-GHRH or saline from 9 to 30 months of age, and the spatial learning and reference memory of animals were assessed by using the Morris water maze and compared with those of 6-month-old animals. Results indicated that spatial memory decreased with age and that chronic [D-Ala2]-GHRH prevented this age-related decrement (24% improvement in the annulus-40 time and 23% improvement in the number of platform crossings compared with saline treated, age-matched controls; p < .05 each). No changes were noted in sensorimotor performance. [D-Ala2]-GHRH attenuated the age-related decline in plasma concentrations of insulinlike growth factor-1 (IGF-1) (p <.05). These data suggest that growth hormone and IGF-1 have important effects on brain function, that the decline in growth hormone and IGF-1 with age contributes to impairments in reference memory, and that these changes can be reversed by the chronic administration of GHRH.

Aging↗

The role of the lateral line and vision on body kinematics and hydrodynamic preference of rainbow trout in turbulent flow.

The ability to detect water flow using the hair cells of the lateral line system is a unique feature found in anamniotic aquatic vertebrates. Fishes use their lateral line to locate prey, escape from predators and form cohesive schooling patterns. Despite the prevalence of complex flows in nature, almost nothing is known about the function of the lateral line and its relationship to other sensory modalities for freely swimming fishes in turbulent flows. Past studies indicate that under certain conditions the lateral line is not needed to swim steadily in uniform flow. This paper examines how the lateral line and vision affect body kinematics and hydrodynamic habitat selection of rainbow trout (Oncorhynchus mykiss) exposed to vortices generated behind a cylinder. Trout Kármán gaiting (i.e. exploiting vortices to hold station in a vortex street) with a pharmacologically blocked lateral line display altered kinematics; body wavelength and wave speed increase compared to control animals. When visual cues are withheld by performing experiments in the dark, almost all Kármán gait kinematics measured for fish with and without a functional lateral line are the same. The lateral line, rather than vision, plays a larger role in affecting body kinematics when trout hold station in a vortex street. Trout show a preference to Kármán gait in the light but not in the dark, which may be attributed to physiological state rather than hydrodynamic or sensorimotor reasons. In the dark, trout both with and without a functional lateral line hold station near the downstream suction region of the cylinder wake (i.e. entraining) and avoid the vortex street. Vision therefore plays a larger role in the preference to associate with a turbulent vortex street. Trout in the light with a blocked lateral line show individual variation in their preference to Kármán gait or entrain. In the dark, entraining trout with an intact lateral line will alternate between right and left sides of the cylinder throughout the experiment, showing an ability to explore their environment. By contrast, when the lateral line is blocked these fish display a strong fidelity to one side of the cylinder and are not inclined to explore other regions of the flow tank. Both entraining and Kármán gaiting probably represent energetically favorable strategies for holding station relative to the earth frame of reference in fast flows. The ability to decipher how organisms collect and process sensory input from their environment has great potential in revealing the mechanistic basis of how locomotor behaviors are produced as well as how habitat selection is modulated.

Animals↗

Problem solving skills in young yellow-crowned parakeets (Cyanoramphus auriceps).

Despite the long divergent evolutionary history of birds and mammals, early avian and primate cognitive development have many convergent features. Some of these features were investigated with a series of tasks designed to assess human infant development. The tasks were presented to young parakeets to assess their means-end problem solving abilities. Examples of these early skills are: attaining and playing with objects, retrieving rewards through use of a stick or rake, or by pulling in rewards on supports or on the ends of strings. Twelve such tasks were presented to 11 young yellow-crowned parakeets ( Cyanoramphus auriceps) to investigate their natural abilities; there was no attempt to train them to do those tasks that they did not spontaneously perform. Six of the birds were parent-raised and five were hand-raised. The birds completed 9 of the 12 tasks, demonstrating all the Piagetian sensorimotor circular reactions, but they failed to hand-watch ("claw-watch"), to stack objects, or to fill a container. Their ordinality on the tasks differed from that of human infants in that locomotion to obtain objects occurred earlier in the avian sequence of development and the mid-level tasks were performed by the two groups of avian subjects in a mixed order perhaps indicating that these abilities may not emerge in any particular order for these birds as they supposedly do for human infants. The hand-raised group needed fewer sessions to complete these means-end tasks.

Animals↗

Impaired prepulse inhibition of acoustic startle in obsessive-compulsive disorder.

BACKGROUND: Animal and clinical studies suggest that impaired sensorimotor gating, as assessed with the prepulse inhibition (PPI) paradigm, may result from dysfunctional frontostriatal brain circuits and from neurochemical alterations which are also implied in the pathophysiology of obsessive-compulsive disorder (OCD). However, there is only preliminary evidence about impaired PPI in OCD so far. METHODS: Acoustic PPI was measured in 30 OCD patients and 30 matched healthy controls with a paradigm using different prepulse intensities. Psychopathology assessment included ratings for obsessions, compulsions, and depression. RESULTS: PPI was reduced in OCD patients, and this deficit was most pronounced for most intense (16 dB(A)) prepulses, where mean PPI was 39.6% in unmedicated patients (n = 4), 45.8% in medicated patients, and 58.9% in controls. No group differences were observed with regard to the habituation of acoustic startle magnitude. Startle measures were generally not associated with clinical measures, although such associations may have been obscured by medication effects. CONCLUSIONS: The present study confirms deficient central inhibitory functioning in patients with OCD and supports the model of deficient frontostriatal circuits in OCD. The relationship of PPI deficits to pharmacological and behavioral treatment and to possible subtypes of OCD merits further study.

Acoustic Stimulation↗

Communication and sensorimotor functioning in children with autism.

This study examined the relationship between sensorimotor functioning and communicative intent in children with autism. Ten children with autism, four verbal and six nonverbal, served as subjects. Sensorimotor functioning was assessed on object permanence, means-end, causality, vocal and gestural imitation, the construction of objects in space and schemes for relating objects. A 2-hr communication sample was also obtained and analyzed for the number and diversity of pragmatic functions expressed. Object permanence was not significantly related to either the diversity or total number of pragmatic functions. Means-end was significantly related to both of these measures, while vocal imitation was significantly related to the total number of pragmatic functions expressed. In addition, means-end was significantly correlated with performance on the vocal and gestural imitation scales.

Autistic Disorder↗

Central nervous system characterization of the new cholecystokininB antagonist LY288513.

The activity of LY288513, an investigational cholecystokinin (CCK)B antagonist, was evaluated in a wide range of pharmacological tests in mice and rats. The anxiolytic benzodiazepine, diazepam, served as a reference standard for LY288513 in many of the tests. In the elevated plus-maze, LY288513 (3, 10 mg/kg, IP; 10, 30 mg/kg, PO) produced an anxiolytic-like action in mice with a magnitude of effect similar to that of diazepam. However, unlike diazepam, LY288513 produced no overt clinical signs and did not affect muscle tone, neuromuscular coordination, or sensorimotor reactivity. Also, in contrast to diazepam, LY288513 did not produce changes in the thresholds for electroshock- or pentylenetetrazol-induced convulsions. High doses of LY288513 (1000 mg/kg, PO) were required to reduce spontaneous activity levels, decrease body temperature, or potentiate the CNS-depressant effects of hexobarbital. LY288513 had no analgesic activity in mouse writhing or tail-flick tests. Electrophysiological studies in anesthetized rats showed that acute administration of LY288513 decreased the number of spontaneously active dopamine neurons in the substantia nigra and ventral tegmental area. However, LY288513 did not produce catalepsy. These data indicate that LY288513 possess both anxiolytic and antipsychotic potential.

Animals↗

The effects of pharmacological doses of 2-deoxyglucose on cerebral blood flow in healthy volunteers.

The effects of glucose deprivation on cerebral blood flow (CBF) have been extensively investigated during insulin-induced hypoglycemia in laboratory animals. Pharmacological doses of glucose analog, 2-deoxyglucose (2DG), is an alternative glucoprivic agent that in contrast to insulin, directly inhibits glycolysis and glucose utilization. Both glucoprivic conditions markedly increase CBF in laboratory animals. How 2DG affects CBF in humans is still undetermined. In the present study we have employed H215O positron emission tomography (PET) to examine the effects of pharmacological doses of 2DG (40 mg/kg) on regional and global cerebral blood flow in 10 brain areas in 13 healthy volunteers. 2DG administration significantly raised regional CBF (rCBF) in the cingulate gyrus, sensorimotor cortex, superior temporal cortex, occipital cortex, basal ganglia, limbic system and hypothalamus. 2DG produced a trend towards elevated CBF in whole brain and frontal cortex, while no changes were observed in the corpus callosum and thalamus. In addition, 2DG significantly decreased body temperature and mean arterial pressure (MAP). Maximal percent changes in hypothalamic rCBF were significantly correlated with maximal changes in body temperature but not with MAP. These results indicate that cerebral glucoprivation produced by pharmacological doses of 2DG is accompanied by widespread activation of cortical and subcortical blood flow and that the blood flow changes in the hypothalamus may be related to 2DG-induced hypothermia.

Adult↗

Locomotor capacity attributable to step training versus spontaneous recovery after spinalization in adult cats.

Locomotor performance, hindlimb muscle activity and gait patterns during stepping were studied in step-trained and non-trained female, adult spinal cats. Changes in locomotor characteristics relative to prespinalization bipedal and quadrupedal stepping patterns were used to evaluate the effects of step training on the capacity to execute full weight-bearing stepping after spinalization. Step training consisted of full weight-bearing stepping of the hindlimbs at the greatest range of treadmill speeds possible at any given stage of locomotor recovery. In the initial stages of training the limbs were assisted as needed to execute successful steps. On the basis of two behavioral criteria, the maximum speed of treadmill stepping and the number of successful steps per unit time, the ability to step was at least 3 times greater in animals trained to step versus those allowed to recover spontaneously, i.e., the non-trained. The greater success in stepping was reflected in several physiological and kinematic properties. For example, the amplitude of electromyograph (EMG) bursts in the tibialis anterior (an ankle dorsiflexor), the amount of extension at the end of both the stance (E3) and swing (E1) phases of the step cycle, and the amount of lift of the hindlimb during swing were greater in step-trained than in non-trained spinal cats. The changes that occurred in response to training reflected functional adaptations at specific phases of the step cycle, e.g., enhanced flexor and extensor function. The improved stepping capacity attributable to step training is interpreted as a change in the probability of the appropriate neurons being activated in a temporally appropriate manner. This interpretation, in turn, suggests that step training facilitated or reinforced the function of extant sensorimotor pathways rather than promoting the generation of additional pathways. These results show that the capacity of the adult lumbar spinal cord to generate full weight-bearing stepping over a range of speeds is defined, in large part, by the functional experience of the spinal cord after supraspinal connectivity has been eliminated. These results have obvious implications with regards to 1) the possibility of motor learning occurring in the spinal cord; 2) the importance of considering "motor experience" in assessing the effect of any postspinalization intervention; and 3) the utilization of use-dependent interventions in facilitating and enhancing motor recovery.

Animals↗

The analysis system COGITAT for the study of cognitive deficiencies in rodents.

COGITAT is an automated hole board system that, following minimal experimental interventions, makes it possible to measure a variety of parameters associated with learning, memory, relearning, cognition, and cognitive shifts, but also changes in exploratory and sensorimotor performance in rodent models. The individual parameters--that is, overall exploratory activity, number of visits (deep in the hole) into or inspections of (at the upper surface) holes, number of baited, unbaited, or previously baited holes visited or inspected, reinspections of or revisits into any holes, number of pellets eaten, time to find pellets, serial order collection (without intermediate inspections or visits), and reference and working memory errors (visits, inspections, or total)--are obtained simultaneously, and the results are immediately available after the end of each experiment. The system appears to be well suited to neurophysiological, neuropharmacological, and gene-technological investigations in rodent models.

Animals↗

Neurodevelopmental outcome at 5 years of age of a national cohort of extremely low birth weight infants who were born in 1996-1997.

OBJECTIVE: Increasing survival of extremely low birth weight (ELBW; birth weight < 1000 g) infants raises a concern regarding the risks of adverse long-term outcome such as cognitive dysfunction. Few studies have reported long-term follow-up of representative regional cohorts. The objective of this study was to assess the 5-year outcome of a prospectively followed national ELBW infant cohort. METHODS: Of all live-born ELBW infants (n = 351) who were delivered in the 2-year period 1996-1997 in Finland, 206 (59%) survived until the age of 5 years. Of these, 103 were born at < 27 gestational weeks (GW). A total of 172 children were assessed with neurocognitive tests (Wechsler Preschool and Primary Scale of Intelligence-Revised and a Developmental Neuropsychological Assessment [NEPSY]). Nine children with cognitive impairment and inability to cooperate in testing were not assessed. Motor development was assessed with a modified Touwen test. RESULTS: The rate of cognitive impairment in the ELBW survivors was 9%. The rate of cerebral palsy was 14% (19% of ELBW infants who were born at < 27 GW). The mean full-scale IQ of the assessed children was 96 +/- 19 and in children of GW < 27 was 94 +/- 19. Attention, language, sensorimotor, visuospatial, and verbal memory values of NEPSY assessment were significantly poorer compared with normal population means. Four percent needed a hearing aid, and 30% had ophthalmic findings. Of 21 children who had been treated with laser/cryo for retinopathy of prematurity, 17 (81%) had abnormal ophthalmic findings. Of the whole cohort, 41 (20%) exhibited major disabilities, 38 (19%) exhibited minor disabilities, and 124 (61%) showed development with no functional abnormalities but subtle departures from the norm. Only 53 (26%) of the total ELBW infant cohort were classified to have normal outcome excluding any abnormal ophthalmic, auditory, neurologic, or developmental findings. Being small for gestational age at birth was associated with suboptimal growth at least until age 5. CONCLUSIONS: Only one fourth of the ELBW infants were classified as normally developed at age 5. The high rate of cognitive dysfunction suggests an increased risk for learning difficulties that needs to be evaluated at a later age. Extended follow-up should be the rule in outcome studies of ELBW infant cohorts to elucidate the impact of immaturity on school achievement and social behavior later in life.

Child Development↗

Non-spatial, motor-specific activation in posterior parietal cortex.

A localized cluster of neurons in macaque posterior parietal cortex, termed the parietal reach region (PRR), is activated when a reach is planned to a visible or remembered target. To explore the role of PRR in sensorimotor transformations, we tested whether cells would be activated when a reach is planned to an as-yet unspecified goal. Over one-third of PRR cells increased their firing after an instruction to prepare a reach, but not after an instruction to prepare a saccade, when the target of the movement remained unknown. A partially overlapping population (two-thirds of cells) was activated when the monkey was informed of the target location but not the type of movement to be made. Thus a subset of PRR neurons separately code spatial and effector-specific information, consistent with a role in specifying potential motor responses to particular targets.

Animals↗

Differential effects of D1 and D2 dopamine receptor antagonists on acute amphetamine- or methamphetamine-induced up-regulation of zif/268 mRNA expression in rat forebrain.

This study investigated the hypothesis that D1 and D2 dopamine receptors interact to regulate the expression of zif/268 mRNA in rat forebrain after an acute injection of amphetamine or methamphetamine. Forty-five minutes and 3 h after a single injection of amphetamine (4 mg/kg i.p.) or methamphetamine (4 mg/kg i.p.), the mRNA expression of zif/268 in dorsal striatum and sensorimotor cortex was increased, as revealed by quantitative in situ hybridization histochemistry. Induction was more intense in striatal patches at 45 min than at 3 h, when a more homogeneous pattern of zif/268 mRNA induction was observed. SCH 23390, a selective D1 receptor antagonist, suppressed, and eticlopride, a D2 receptor antagonist, elevated, constitutive zif/268 mRNA levels in the striatum, but neither antagonist had a significant effect on the constitutive expression of zif/268 in soensorimotor cortex. Pretreatment with SCH 23390 completely blocked the stimulant-induced zif/268 expression in striatum and partially blocked the stimulant-induced zif/268 expression in cortex. Pretreatment with eticlopride augmented zif/268 mRNA expression in patch and matrix compartments of dorsal and ventral striatum 45 min after amphetamine or methamphetamine injection. However, at 3 h, eticloprides completely blocked amphetamine- and methamphetamine-stimulated zif/268 mRNA in dorsomedial, but not dorsolateral, striatum. In addition, eticlopride partially blocked cortical zif/268 induction by both amphetamines. Both antagonists prevented stimulant-induced hyperlocomotion and stereotypies. These results demonstrate that D1 and D2 receptors in mesolimbic/mesostriatal pathways both regulate amphetamine- and methamphetamine-stimulated behaviors and zif/268 mRNA expression. Furthermore, the effect of D2 receptor blockade on zif/268 expression was found to be contingent on the time interval investigated after psychostimulant administration.

Amphetamine↗