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Normal development of tyrosine hydroxylase and serotonin immunoreactive fibers innervating anterior cingulate cortex and visual cortex in rabbits exposed prenatally to cocaine.

Anterior cingulate cortex develops abnormally in rabbits exposed to cocaine in utero but visual cortex is normal. The interactions of cocaine with the dopamine, norepinephrine and serotonin systems makes each a potential candidate for influencing these developmental effects. Here, we report no differences in the distribution and density of serotonin and tyrosine hydroxylase-immunoreactive fibers in the anterior cingulate cortex in postnatal rabbits exposed prenatally to cocaine or saline. Because the pattern and extent of cortical innervation by these systems appears normal, the data suggest that the effects of prenatal exposure to cocaine may involve changes in monoamine signaling distinct from morphological reorganization of the cortical afferents.

Animals↗

Neonatal lesion of the rat's frontal cortex and subsequent transplantation of embryonic frontal cortex: evidence of appropriate synaptic integration of the graft neurons within the host thalamo-fronto-striate circuit.

Previous observations in intact rats have indicated that axons from the ventrolateral thalamic nucleus (VL) establish direct axo-somatic or axo-dendritic contacts onto frontal cortical neurons projecting to the striatum. The embryonic frontal cortex was grafted into the damaged frontal cortex of newborn rats to study the capacity of homotopic transplants to restore the thalamo-fronto-striate pathway. Several months later, grafted neurons projecting to the striatum were identified by injecting a retrograde neurotracer (subunit b of the cholera toxin) into the ipsilateral caudate putamen. In the same animal, axons and terminations from the VL were labeled within the transplant with an anterograde neurotracer (Phaseolus vulgaris leuco-agglutinin) injected into the ipsilateral VL. The findings show that VL axons establish direct synaptic contacts onto grafted neurons projecting to the striatum. Although the synaptic contacts were scarce in the transplants, their organization was similar to that observed in intact rats. The contacts were axo-somatic or axo-dendritic. Our observations for the first time indicate that synaptic contacts are formed in cortical grafts and that fetal frontal cortex is susceptible to develop appropriate synaptic integration within the host thalamo-fronto-striate system.

Animals↗

Effects of early environments on monkey cortex neuroanatomical changes following somatomotor experience: effects on layer III pyramidal cells in monkey cortex.

Sixteen infant stumptail monkeys were reared to 6 months under four conditions. Behaviors and cortical neuroanatomy were compared. Earlier studies showed effects on stellate cell dendrites. Here are reported the results in six cortical areas on basilar dendrites of layer III pyramidal cells. Basilar dendrites show significantly larger numbers (p less than .05) of branching for motor I cortex under condition 3 associated with the greatest skills and amount of activity in climbing, swinging, and grasping of objects. Visual cortex was not significantly altered by the rearing conditions, but the basilar dendrites showed less branching than in the five other areas of cortex sampled. It is concluded that genetic factors are responsible for the major growth patterns and that environmental factors contribute to quantitative increases or decreases in the branching of dendrites and therefore the finer tuning of neural interconnections.

Animals↗

Information cascade from primary auditory cortex to the amygdala: corticocortical and corticoamygdaloid projections of temporal cortex in the rat.

Corticocortical and corticoamygdaloid connections of temporal cortext and perirhinal cortex (PRh) were examined in the rat with the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). Iontophoretic injections of PHA-L into area TE1 resulted in columnar axonal terminations in surrounding and contralateral regions of temporal neocortex and in the striatum, but not in the amygdala. Within temporal neocortex, labeled fibers were present locally in adjacent regions of TE1, as well as in TE2d, TE1v, TE3v, and TE2c. Injection of cortical areas TE1v, TE3v, and TE2c, which received projections from TE1, or injections of perirhinal periallocortex, which received projections from TE1v, TE2v, and TE3v, resulted in projections to the amygdala. The pattern of corticocortical and corticoamygdaloid projections differed among the divisions of auditory cortex. TE1 exhibited extensive ipsilateral and contralateral projections to temporal cortical regions and no projections to the amygdala. In contrast, areas of temporal neocortex ventral and posterior to TE1, including TE1v, TE3v, TE2c, and PRh, had more limited ipsi- and contralateral corticocortical projections but had an increased connectivity with the subcortical forebrain, especially the lateral nucleus of the amygdala (AL). There was a topographic organization to the AL afferents. The dorsal subdivision of AL received projections from TE1v, TE3v, TE2c, and PRh, while the ventrolateral division received projections from TE3v, TE2c, and PRh. The ventromedial division received projections only from PRh, which, unlike other temporal cortical areas, also projected to the basolateral and basomedial nuclei of the amygdala. These findings define the complete sequence of connections linking primary auditory cortex with the amygdala in the rat. In addition, the findings indicate that the ventral portion of TE1, designated TE1v, has connections that distinguish it from dorsal TE1, namely, dense projections to AL and a diminished number of corticocortical projections ipsilaterally and contralaterally. Finally, the results suggest a topographic organization to the cortical terminations within the amygdala.

Amygdala↗

Perirolandic cortex in infants: signal intensity on MR images as a landmark of the sensorimotor cortex.

PURPOSE: To correlate the perirolandic low signal intensity seen on T2-weighted magnetic resonance (MR) images in neonates and infants with the anatomically located sensorimotor cortex. MATERIALS AND METHODS: Axial T2-weighted MR images of 146 consecutive patients less than 6 months old were reviewed. The sensorimotor cortex was located by identifying the central sulcus. Two independent readers attempted to identify the central sulcus using two anatomic methods independently and in combination. The location of the central sulcus was compared with that of the perirolandic low signal intensity. RESULTS: Seventy-two normal hemispheres in 36 patients and 91 abnormal hemispheres in 47 patients showed clear perirolandic low signal intensity. The central sulcus was located anatomically in 70 and 72 normal hemispheres (97% and 100%, respectively) and 90 and 91 abnormal hemispheres (99% and 100%, respectively). In all normal hemispheres, the identified central sulcus correlated with the perirolandic low signal intensity. In contrast, an apparent mismatch was found in two hemispheres in a patient with Dandy-Walker syndrome. CONCLUSION: The perirolandic low signal intensity seen on T2-weighted MR images is located exactly in the anatomic sensorimotor cortex in normal brains, whereas a mismatch can occur in abnormal brains.

Bacterial Infections↗

Functional magnetic resonance imaging at 1 T: motor cortex, supplementary motor area and visual cortex activation.

Functional activation of the brain has been visualized using magnetic resonance imaging (MRI). Early studies used echo planar imaging and magnetic fields of 2 T and above. However, recent studies have successfully shown the activation of visual and motor areas of the brain using conventional clinical 1.5 T MRI systems. The purpose of the present study was to replicate these studies at a lower field strength. Eight motor and two visual activation studies were performed using a 1 T clinical scanner. Activation was seen in the contralateral motor cortex during motor stimulation in six of the eight volunteers. Activation was also documented within the contralateral supplementary motor area in four of the six volunteers with motor cortex activation. The supplementary motor area was located in the posteromedial aspect of the superior frontal gyrus. Both volunteers subjected to photic stimulation showed activation within the visual cortex. Results show that functional imaging can be successfully carried out with a 1 T clinical scanner. The size of the image intensity on activation change suggests that contrast may not be due solely to susceptibility changes.

Brain Mapping↗

Fetal frontal cortex transplanted to injured motor/sensory cortex of adult rats. I. NADPH-diaphorase neurons.

Fetal frontal cortex from 18-d-old embryonic rat brain was transplanted into cavities of juvenile host motor/sensory cortex. Two to seven months later, sections were reacted for NADPH-diaphorase (NADPH-d) enzyme histochemistry. NADPH-d-positive neurons survived in 11 of 13 grafts. All but one of the transplants had reduced numbers of these neurons, although in 3 transplants the reductions were moderate and not statistically significant. The distribution and morphology of NADPH-d neurons within most grafts was comparable to that of NADPH-d neurons in normal host cortex. At the margin of the 2 transplants with no NADPH-d neuronal perikarya, NADPH-d fibers crossed from host to transplant as far as a millimeter into the transplant, and on rare occasions, the host neurons that gave rise to these fibers were identified. This suggests that host-transplant interactions are possible. One transplant had an abnormally large number of NADPH-d-positive neurons and fibers, possibly due to selective survival of these neurons. The data reported here for NADPH-d in cortical transplants may also apply to neuropeptide Y (NPY), since nearly all neocortical NPY neurons also contain NADPH-d.

Animals↗

A positron emission tomographic study of subthalamic nucleus stimulation in Parkinson disease: enhanced movement-related activity of motor-association cortex and decreased motor cortex resting activity.

BACKGROUND: Long-term high-frequency stimulation of the subthalamic nucleus (STN) improves akinesia in Parkinson disease. The neural correlates of STN stimulation are not well understood. Positron emission tomography can be applied to the in vivo study of the mechanisms of deep brain stimulation. OBJECTIVE: To study changes in regional cerebral blood flow as an index of synaptic activity in patients with Parkinson disease with effective STN stimulation on and off during rest and movement. METHODS: Eight patients with Parkinson disease who had electrodes implanted in the STN underwent 12 measurements of regional cerebral blood flow with water O 15 positron emission tomography at rest and during performance of paced freely selected joystick movements, both with and without STN stimulation (3 scans per experimental condition). Motor performance and reaction and movement times were monitored. Statistical parametric mapping was used to compare changes in regional cerebral blood flow between conditions and differences in activation. RESULTS: All patients showed improvement in reaction and movement times during scans with the stimulator on. As predicted, increases in activation of rostral supplementary motor area and premotor cortex ipsilateral to stimulation were observed when stimulation was on during contralateral movement (P<.001). Unpredicted observations included decreases in regional cerebral blood flow in primary motor cortex at rest induced by STN stimulation. CONCLUSION: Stimulation of the STN reduces the movement-related impairment of frontal motor association areas and the inappropriate motor cortex resting activity in Parkinson disease.

Adult↗

Transplantation of human cortex with Alzheimer's disease into rat occipital cortex; a model for the study of Alzheimer disease.

Senile dementia of the Alzheimer type (SDAT) is a major problem in the human senescent population. As this pathology cannot be reproduced in animals, research into its development is greatly impeded. The technique of implantation of the nervous tissue has been utilized in order to establish an animal model and to test the possible existence of a transmissible agent. When human temporal cortex with Alzheimer's disease is implanted in the occipital cortex of 7-week-old rats, human cerebral tissue containing abundant tangles induces in the receiver cortex a reactive fibrous gliosis. In the processes of the astrocytes, twisted filaments are evident among bundles of normal filaments. These alterations could be induced by the metabolising of abnormal filament subunits or by some infectious agent introduced by the implant.

Aged↗

Plastic reorganizations of the receptive fields of neurons of the auditory cortex and the medial geniculate body induced by microstimulation of the auditory cortex.

The receptive fields of neurons (RFs) whose activity was simultaneously recorded at several loci of the auditory cortex (AC) and in the medial geniculate body (MGB) were investigated before and after intracortical microstimulation (ICMS). Three types of neurons of the AC and MGB were distinguished on the basis of the character of the RFs: mono-, bi-, and polymodal. The RFs of the neighboring neurons in the AC (or in the MGB) could differ, while the RFs of remote neurons of the AC could be similar. The microstimulation of the AC could lead to changes in the RFs of neurons in the stimulated locus and neighboring loci of the AC, as well as in the loci of the MGB tonotopically associated with them. It is hypothesized that long-term modification of the efficiency of synaptic transmission between different elements of the cortex-thalamus-cortex circuit which arises as the result of the circulation of impulses along this chain during ICMS may be the mechanism underlying the observed changes in the RFs of AC and MGB neurons.

Animals↗

Specialisation within the prefrontal cortex: the ventral prefrontal cortex and associative learning.

This paper provides evidence that the ventral prefrontal cortex plays a role in the learning of tasks in which subjects must learn to associate visual cues and responses. Imaging with both positron-emission tomography (PET) and functional magnetic-resonance imaging (fMRI) reveals learning-related increases in activity when normal subjects learn visual associative tasks. Evidence is also presented from an event-related fMRI study that activity in this area is time-locked both to the presentation of the visual stimuli and also to the time of the motor response. Finally, it is shown in a study of monkeys that removal of the ventral prefrontal area 12 (including 45 A) impairs the ability of monkeys to relearn a visual associative task (visual matching), even though there were no demands on working memory. It is, therefore, proposed that the ventral prefrontal cortex constitutes part of the circuitry via which associations are formed between visual cues and the actions or choices that they specify. On the basis of the existing anatomical and electrophysiological data, it is argued that the prefrontal cortex is the only area that can represent cues, responses and outcomes.

Animals↗

Intrauterine cocaine exposure of rabbits: persistent elevation of GABA-immunoreactive neurons in anterior cingulate cortex but not visual cortex.

The effects of prenatal cocaine exposure on the development of the rabbit cerebral cortex were studied. Two cortical areas were compared: primary visual cortex (VC) and anterior cingulate cortex (ACC). ACC was selected because behavioral deficits observed in cocaine-exposed infants suggest the involvement of ACC. In addition, ACC receives dense dopaminergic innervation and cocaine's action in inhibiting the re-uptake of dopamine is believed to underly the rewarding properties of cocaine. VC was selected as a control area because there is no evidence of behavioral deficits associated with visual perception in cocaine-exposed infants, and because VC receives minimal dopaminergic innervation. Two aspects of cortical development were studied: (i) cortical morphology, growth and cytoarchitectonic organization; and (ii) the development of the GABAergic neurotransmitter system. Measures of postnatal cortical growth, including cortical lamination, cell number and soma size, were compared in cocaine-exposed or control (saline) rabbits aged P5-P60. There was no difference between cocaine and saline animals in any of these parameters, and cortical cytoarchitecture appeared normal. However, despite the absence of major abnormalities in cortical development, we found that the number of GABA-immunoreactive neurons in cocaine-exposed animals was significantly higher than normal in ACC. This effect was highly consistent, was present in all laminae and at all ages studied, and persisted into maturity (P60). In contrast, in VC, the number of GABA-immunoreactive neurons in cocaine-exposed animals did not differ from normal. We suggest that increased GABA immunoreactivity may reflect a compensatory response to excessive excitatory input to ACC. A change in the balance of excitation and inhibition in ACC, reflecting 'noisy' or dysfunctional intracortical circuitry, may underly the emotional lability and attentional deficits characteristically described in infants exposed in utero to cocaine.

Animals↗

Contribution of striate cortex and the superior colliculus to visual function in area MT, the superior temporal polysensory area and the inferior temporal cortex.

We studied the visual responses of single neurons in three extra-striate visual areas of the macaque following lesions of striate cortex, lesions of the tecto-pulvinar system or both. After striate lesions, there was (a) considerable specific activity remaining in area MT including direction selectivity, (b) only non-specific activity in the superior temporal polysensory area (STP), and (c) no visual responsiveness at all in inferior temporal cortex (IT). In animals with striate lesions, interruption of the tecto-pulvinar pathway eliminated the residual visual activity in MT and STP that survived the striate lesions. Interruption of the tecto-pulvinar pathway alone had little or no effect on visual evoked activity in any of the three areas. These results are related to the relative dependence of visual responsiveness in MT, STP and IT on striate cortex and the superior colliculus, to differences between the dorsal and ventral cortical processing streams, and to neural mechanisms underlying blind sight.

Animals↗

Loss of hybridizable ribosomal DNA from human post-mitotic tissues during aging: II. Age-dependent loss in human cerebral cortex--hippocampal and somatosensory cortex comparison.

DNA was isolated from the hippocampal and from the somatosensory cortex of 13 humans (at autopsy). In both the cortex and hippocampus, the loss of ribosomal DNA (rDNA), as measured through hybridization in the liquid phase, approximates about 0.9% per year. The r value for somatosensory cortex was about -0.7 and that for the hippocampus was about -0.91. The correlation coefficient between the sets of two samples derived from the same individual (two different areas) in +0.945. These results are consistent with those reported concurrently for human myocardium and with earlier studies conducted with beagle dogs, in which only post-mitotic tissues (brain, heart and skeletal muscle) showed measurable decrements in these key genes. To the degree that the synthesis of new proteins is essential for sustained mental activity, these results are consistent with the observations that Nissl substance is more slowly replenished, following exhaustive work by motor cortical cells, and the fact that many older persons experience mental fatigue during continuous mental work at earlier times than do younger persons. The mechanism of loss is not certain, but may well be related to inadequacies in DNA repair systems, thereby allowing deletion of tandemly duplicated genes through cross-over "episome" formation, followed by degradation of the excised DNA segments. The ratio of loss of rDNA hybridizability in human and dogs in about 1 to 7, which approximates the relative ratios of their lifespans (reciprocals).

Adolescent↗

Comparisons of hemi-inattention produced by unilateral lesions of the posterior parietal cortex or medial agranular prefrontal cortex in rats: neglect, extinction, and the role of stimulus distance.

Neglect in human and non-human primates has been demonstrated following unilateral lesions of both posterior parietal and prefrontal areas. While it has now been well established that a unilateral lesion of the rodent analog of dorsolateral prefrontal cortex, medial agranular cortex (AGm), results in neglect, the effects of unilateral damage restricted to rodent posterior parietal cortex (PPC) have not been examined in detail. The current study assessed rats with unilateral lesions of PPC or AGm on their ability to orient to unilateral and bilateral stimulation. Since it has been proposed in both the primate and rodent literatures that frontal areas may be responsible for the perception of near space while parietal areas may be responsible for far space, stimuli were presented at two different distances. Lesions of PPC and AGm resulted in severe neglect relative to control operates, with both PPC and AGm operates manifesting severe hemi-inattention and allesthesia relative to control operates. After behavioral recovery from neglect there was no evidence of extinction to bilateral simultaneous stimulation. While neglect to visual stimuli predominated in unilateral PPC operates, unilateral AGm operates had severe neglect in all modalities. In addition, while both left and right PPC operates showed contralesional neglect, AGm operates demonstrated the lateralized differences in neglect reported in previous studies. All groups demonstrated an approximately equivalent level of neglect to stimuli presented at the two different distances, and thus failed to support the suggestion of a peripersonal-extrapersonal dichotomy between frontal and parietal areas in rodents.

Animals↗

Lack of effect of lesions in the anterior cingulate cortex and retrosplenial cortex on certain tests of spatial memory in the rat.

The effects of cytotoxic lesions in either the anterior cingulate cortex or the retrosplenial cortex were compared with those of fornix lesions on three tests of spatial memory. Two of the tasks, delayed nonmatching-to-position and spatial reversal learning, were tested in an automated apparatus. The third task, forced alternation, was tested in a T-maze. Neither anterior cingulate nor retrosplenial cortex damage produced any significant impairment on the three tasks. In contrast, rats with fornix lesions (hippocampal system damage) were markedly impaired on all three tasks. The results, which were considered in the light of proposals for a hippocampal--anterior thalamic--cingulate system that is important for spatial memory, suggest that neither of the cingulate regions involved in this study form a critical subcomponent of this proposed system. It is therefore assumed that the cingulate cortices are only critical for certain classes of spatial problem. It is also suggested that in some previous studies the effects of inadvertent damage to the cingulum bundle may have contributed to the apparent effects of cingulate lesions.

Animals↗

Efferents of frontal or occipital cortex grafted into adult rat's motor cortex.

Phaseolus vulgaris leucoagglutinin (PHA-L) was used to examine the efferent connectivity of embryonic (E16) frontal (homotopic) or occipital (heterotopic) neocortical transplants placed into--or in the vicinity of--lesion cavities made in the frontal cortex of adult recipients. Homotopic transplants projected towards the host sensorimotor cortex and, in most cases, into the lateral caudate-putamen (CPu). Heterotopic transplants projected into the anterior cingulate cortex and, in most cases, distributed terminals into the medial CPu. It is suggested that embryonic neocortical tissue placed into a damaged cortical site of an adult recipient develops a pattern of efferents corresponding to its cortical origin.

Animals↗

Dopaminergic innervation of the primary visual cortex in the rat, and some correlations with human cortex.

Dopaminergic terminals have been identified in the primary visual cortex with three techniques; immunocytochemistry with an anti-dopamine antiserum, retrograde axonal transport techniques using unconjugated wheat germ agglutinin and HPLC determination of catecholamines and metabolites in microdissected sub-regions of occipital cortex in the rat. The results demonstrate a specific dopaminergic innervation, arising from the ventral tegmental area, which is found mainly in laminae VI and V, but with minor innervation also in lamina I. Dopaminergic innervation to adjacent cortical regions is also described. Neurochemical data from post-mortem human material suggests that a similar innervation exists in man. An analysis of the distribution of dopaminergic fibres in relation to the known connections and possible functions of the deep laminae of visual cortex suggests that dopaminergic axons may participate in the corticofugal control of visual afferent pathways.

Aged↗