Cerebrospinal fluid reconstitution via a perfusion-based cadaveric model: feasibility study demonstrating surgical simulation of neuroendoscopic procedures.

Cadaveric surgical simulation carries the advantage of realistic anatomy and haptic feedback but has been historically difficult to model for intraventricular approaches given the need for active flow of CSF. This feasibility study was designed to simulate intraventricular neuroendoscopic approaches and techniques by reconstituting natural CSF flow in a cadaveric model. In 10 fresh human cadavers, a simple cervical laminectomy and dural opening were made, and a 12-gauge arterial catheter was introduced. Saline was continuously perfused at physiological CSF pressures to reconstitute the subarachnoid space and ventricles. A neuroendoscope was subsequently inserted via a standard right frontal bur hole. In 8 of the 10 cadavers, adequate reconstitution and endoscopic access of the lateral and third ventricles were achieved. In 2 cadavers, ventricular access was not feasible, perhaps because of a small ventricle size and/or deteriorated tissue quality. In all 8 cadavers with successful CSF flow reconstitution and endoscopic access, identifying the foramen of Monro was possible, as was performing septum pellucidotomy and endoscopic third ventriculostomy. Furthermore, navigation of the cerebral aqueduct, fourth ventricle, prepontine cistern, and suprasellar cistern via the lamina terminalis was possible, providing a complementary educational paradigm for resident education that cannot typically be performed in live surgery. Surgical simulation plays a critical and increasingly prominent role in surgical education, particularly for techniques with steep learning curves including intraventricular neuroendoscopic procedures. This novel model provides feasible and realistic surgical simulation of neuroendoscopic intraventricular procedures and approaches.

Working memory performance and thalamus microstructure in healthy subjects.

Research on the neural basis of working memory (WM) has generally focused on cortical regions, specifically frontal and parietal areas. Comparatively, evidence of a possible involvement of deep gray matter structures, that are parts of cortico-cortical circuits linking anterior and posterior cortical areas, is far less clear. The goal of the present study is to test the hypothesis that individual structural variations within deep gray matter structures may affect the cortical networks involved in WM. To this aim, a large sample (n=181) of healthy subjects underwent a high-resolution structural magnetic resonance imaging (MRI) and a diffusion tensor imaging (DTI) scan protocol. Data of micro- (mean diffusivity, MD) and macro- (volume) structural variations of six bilateral deep gray matter structures (thalamus, caudate nucleus, putamen, hippocampus, amygdala and pallidum) and lateral ventriculi volume were analyzed in association with score in a WM (the so-called n-back task) and other neuropsychological tasks. Results showed that increased MD of bilateral thalami was the only structural parameter that significantly correlated with reduced WM performance. In particular, a voxel-by-voxel analysis revealed that the greater percentage of voxels showing significant anticorrelation between WM score and MD values were localized in those thalamic nuclei projecting to prefrontal and posterior parietal cortices. Results highlight the specific involvement of thalamus microstructure, not volume, in modulating WM performance, possibly by regulating the connections among cortical areas that are recruited during WM tasks.

Characteristic features of a nerve primo-vessel suspended in rabbit brain ventricle and central canal.

Bonghan theory was proposed by Bonghan Kim to illustrate the anatomy and physiology of the acupuncture meridian system. One of his astonishing claims was the physical presence of the nerve primo-vessel, which can be involved with a regenerating system of nerves. Our previous work has shown that there is a nerve primo-vessel in brain ventricles and the central canal of the spine of a rabbit. In this study, confocal laser scanning microscopy, transmission electron microscopy, and high voltage electron microscopy demonstrated that a nerve primo-vessel comprised DNA particles, other microparticles, and rod-shaped nuclei encircled by helix-shaped actins. The nerve primo-vessel had acridine orange-stained DNA particles that varied in size and were in parallel. These characteristics of the nerve primo-vessel are crucial for a comprehensive understanding of their function in the central nervous system, which may be associated with nerve regeneration.

MR quantitation of volume and diffusion changes in the developing brain.

BACKGROUND AND PURPOSE: Brain volume and diffusion change during maturation. Quantitation of these changes may be helpful in understanding normal brain development. We used diffusion-weighted imaging to characterize the volumetric and diffusion changes in vivo. METHODS: We recruited 30 pediatric volunteers (aged 1 month-17 years; 14 male, 16 female). Diffusion was measured in three orthogonal directions with a b value of 1000 s/mm2. The diffusion parameters from the entire brain were calculated and fitted to a triple gaussian model. In addition, region-of-interest measurements were made in caudate, thalamus, genu and splenium of the corpus callosum, and periventricular white matter (PVWM). The brain volume was measured by counting pixels and by using the model. RESULTS: Water diffusion of the whole brain, caudate, thalamus, genu and splenium of the corpus callosum, and PVWM decreased during maturation, with the most significant change within the first 2 years. Robust negative correlations were found between age and the measured average diffusion constant (Dav) values in each of the measured locations (P <.005). Volumes of different cerebral compartments and the total intracranial volume (ICV) increased rapidly during the first 2 years of life and then had a slower growth process through adolescence. Age was correlated with the ICV and the volume of each brain compartment (P <.005). CONCLUSION: Brain diffusion decreases and brain volume increases during maturation, with the most significant changes occurring within the first 2 years of life. The brain model used in this study provides a good estimate of the increasing brain volume.

Postnatal glucocorticoid exposure alters the adult phenotype.

We examined the effect of six doses of dexamethasone (Dex) administered daily (2-7 days of age) to postnatal rats on body weight gain, food and water intake, peripheral hormonal/metabolic milieu, and hypothalamic neuropeptides that regulate food intake. We observed a Dex-induced acute (3 days of age) suppression of endogenous corticosterone and an increase in circulating leptin concentrations that were associated with a decrease in body weight in males and females. Followup during the suckling, postsuckling, and adult stages (7-120 days of age) revealed hypoleptinemia in males and females, and hypoinsulinemia, a relative increase in the glucose-to-insulin ratio, and a larger increase in skeletal muscle glucose transporter (GLUT 4) concentrations predominantly in the males, reflective of a catabolic state associated with a persistent decrease in body weight gain. The increase in the glucose-to-insulin ratio and hyperglycemia was associated with an increase in water intake. In addition, the changes in the hormonal/metabolic milieu were associated with an increase in hypothalamic neuropeptide Y content in males and females during the suckling phase, which persisted only in the 120-day-old female with a transient postnatal decline in alpha-melanocyte-stimulating hormone and corticotropin-releasing factor. This increase in neuropeptide Y (NPY) during the suckling phase in males and females was associated with a subsequent increase in adult food intake that outweighed the demands of body weight gain. In contrast to the adult hypothalamic findings, cerebral ventricular dilatation was more prominent in adult males. We conclude that postnatal Dex treatment causes permanent sex-specific changes in the adult phenotype, setting the stage for future development of diabetes (increased glucose:insulin ratio), obesity (increased NPY and food intake), and neurological impairment (loss of cerebral volume).

Manual and automated measurement of the whole thalamus and mediodorsal nucleus using magnetic resonance imaging.

The thalamus is an important relay structure in the brain that may be relevant to a variety of brain diseases. It is divided into multiple subnuclei with different cortical connections. The medial dorsal (MD) nucleus is particularly important because it forms key connections with the prefrontal cortex. The current study reports precise and efficient methods for measuring the whole thalamus and the MD with MRI that have a high degree of interrater reliability. A multispectral image acquisition and novel image processing technique were used to improve structure visibility. The tricolor image assigns a color to each of the T1, T2, and PD weighted images, represented by red, green, and blue, respectively. The manually defined regions were then used to train an artificial neural network (ANN) to automatically define both the whole thalamus and the MD. The ANN provides an efficient automated method, making studies using larger sample sizes more feasible.

Structural brain abnormalities in chronic schizophrenia at the extremes of the outcome spectrum.

OBJECTIVE: This study investigated the relationship between outcome and structural brain abnormalities in schizophrenia. METHOD: Intracranial volume and volumes of the cerebrum, gray and white matter, lateral and third ventricles, frontal lobes, thalamus, and cerebellum were measured in 20 patients with a poor outcome, 25 with a favorable outcome, and 23 healthy comparison subjects with magnetic resonance imaging. RESULTS: Thalamic volume was significantly smaller both in poor-outcome patients and good-outcome patients. In contrast, only poor-outcome patients displayed significantly smaller cerebral gray matter, particularly prefrontal, and enlargement of the lateral and third ventricles. No significant differences were found for intracranial, cerebellar, or cortical CSF volumes. CONCLUSIONS: Smaller thalamic volumes in schizophrenia may reflect a greater susceptibility for the disorder and seem unrelated to outcome. In contrast, gray matter volume loss of the cerebrum, particularly in the frontal lobes, and lateral and third ventricular enlargement appear related to outcome in schizophrenia.

Succinic dehydrogenase histochemistry reveals the location of the putative primary visual and auditory areas within the dorsal ventricular ridge of Sphenodon punctatus.

In turtles, crocodilians, lizards and snakes, the dorsal ventricular ridge (DVR) is a nuclear cell mass that contains distinct visual and auditory thalamorecipient cell groups. In the tuatara (Sphenodon punctatus), the DVR is not organized into diverse cell groups but instead possesses a trilaminar cytoarchitecture resembling that characteristic of the telencephalic cortex in reptiles. To determine if visual and auditory fields might also be present in the DVR of Sphenodon punctatus, we used succinic dehydrogenase (SDH) histochemistry, which has been shown to delineate the visual and auditory fields of the DVR in turtles, crocodilians and lizards. We also used acetylcholinesterase (AChE) histochemistry to determine the boundary between the DVR and the basal ganglia in Sphenodon. We found an SDH-rich region in the neuropil ventral to the cell plate of the rostrolateral DVR and a slightly less intense SDH-rich zone in the neuropil deep to the cell plate of the ventromedial DVR. These SDH-rich zones appear to be located at the apical dendrites of the neurons of the adjacent cell plate. These SDH-rich zones were clearly located within the DVR and were distinct from the AChE-rich striatal part of the basal ganglia, which occupied the ventrolateral wall of the telencephalon. Based on findings in other reptiles, it seems likely that the SDH-rich zone in rostrolateral DVR represents the zone of termination of nucleus rotundus visual input to the DVR, whereas the zone in ventromedial DVR represents the zone of termination of nucleus reuniens auditory input. Because a trilaminar DVR such as that in Sphenodon might be the primitive DVR condition for reptiles, our results suggest that the cytoarchitecture of the DVR and the synaptic organization of its thalamic sensory input in the common ancestor of living reptiles might have been much like of the dorsal cortex.

Adhesio interthalamica in male patients with schizophrenia.

OBJECTIVE: The authors investigated whether absence of the adhesio interthalamica in patients with schizophrenia constitutes a marker of early developmental neuropathological changes. METHOD: Thirty male patients with schizophrenia and 30 healthy male subjects were recruited for study. Magnetic resonance imaging was performed, and the presence or absence of the adhesio interthalamica was determined for each subject. The length and volume of the third ventricle were also measured. RESULTS: No differences in the presence or absence of the adhesio interthalamica were found between patients with schizophrenia and normal comparison subjects. Patients without the adhesio interthalamica had significantly higher scores for negative symptoms than patients with the adhesio interthalamica. There was no correlation between absence of the adhesio interthalamica and length and volume of the third ventricle in either patients or comparison subjects. CONCLUSIONS: The findings suggest that patients with schizophrenia who do not have the adhesio interthalamica are characterized by more severe negative symptoms.

Quantitative study of signal hyperintensities on T2-weighted magnetic resonance imaging in late-onset schizophrenia.

OBJECTIVE: The authors investigated the extent and distribution of signal hyperintensities on T2-weighted magnetic resonance imaging (MRI) of the brains of subjects with late-onset schizophrenia. METHOD: The study group consisted of 25 subjects with DSM-III-R schizophrenia and onset at age 50 or more years (late-onset schizophrenia) matched group-wise with 24 subjects with early-onset schizophrenia and 30 psychiatrically healthy volunteers. The subjects underwent clinical and neuropsychological assessments and MRI scans. Transaxial T2-weighted and proton-density images were analyzed manually for signal hyperintensities in cerebral and cerebellar white matter, the basal ganglia, thalamus, and brainstem, and quantitative measures were obtained. RESULTS: Subjects with late-onset schizophrenia had greater periventricular hyperintensities measured as widths of periventricular rims and frontal and occipital caps than the two comparison groups. Hyperintense signals elsewhere in the white matter and in the basal ganglia and brainstem did not differ between groups, but the late-onset schizophrenia group had more signal hyperintensities in the thalamus than the normal comparison group. Signal hyperintensities in the frontal-subcortical circuit regions, when considered together, did not differ between groups. Periventricular hyperintensities had significant negative correlations with intelligence, memory, and frontal-executive functioning in the total group. CONCLUSIONS: The finding of increased periventricular hyperintensities and thalamic signal hyperintensities in late-onset schizophrenia suggests the possibility that cerebrovascular disease, in an interaction with some incompletely understood vulnerability factors, may play a role in the pathogenesis of schizophrenia with onset in advanced age.

Topographic anatomy of the cochlear nuclear region at the floor of the fourth ventricle in humans.

OBJECT: The development of appropriate methods to stimulate the dorsal and ventral cochlear nucleus by means of an auditory brainstem implant in patients with acquired bilateral anacusis requires a detailed topoanatomical knowledge both of the location and extension of the nuclear surface in the fourth ventricle and lateral recess and of its variability. The goal of this study was to provide that information. Anatomically, it is possible to use a midline surgical approach to the fourth ventricle rather than the translabyrinthine and suboccipital routes of access used hitherto. This is especially useful if severe scarring, which occurs as a result of tumor removal in the cerebellopontine angle, make the orientation and placement of an auditory brainstem implant via a lateral surgical approach difficult. There have been only a few studies, involving single cases and small series of patients, in which the focus was the exact extension of the cochlear nuclei, whose microsurgically relevant position in relation to the surface structures is not known in detail. METHODS: Landmarks that are important for the placement of an auditory brainstem implant through the fourth ventricle were examined and measured in a large series of 28 formalin-fixed human brainstems. In all cases, these examinations were supplemented by addition of a histological section series. For the first time values of unfixed fresh brainstem tissue were determined. Anatomical features are discussed with regard to their possible neurosurgical relevance, taking into account inter- and intraindividual variability. CONCLUSIONS: The midline approach would provide an opportunity to stimulate the whole area of the dorsal as well as the ventral cochlear nucleus with an auditory brainstem implant.

Role of acoustic striae in hearing: reflexive responses to elevated sound-sources.

This report is the fourth in a series describing the results of ablation-behavior experiments directed to the ascending output of the cochlear nuclei as it is conducted centrally within the acoustic striae. This fourth report focuses on the unique physiology of the fusiform or 'output' cells of the dorsal cochlear nucleus whose axons course through the dorsal acoustic stria (DAS). Because electrophysiological studies have shown that the cues for sensing the elevation of a sound source would seem to be best analyzed by the dorsal cochlear nucleus and projected centrally via its DAS, we tested normal cats and cats deprived of DAS for their ability to orient to elevated sources of broad-band noise. For behavioral testing, we made use of reflexive or unconditioned orienting responses to elevated sound sources using a similar method to one we have used previously for azimuth testing (Thompson GC, Masterton RB. Brainstem auditory pathways involved in reflexive head orientation to sound. J Neurophysiol 1978;41:1183-1202). The results show that cats deprived of their DAS do indeed have a marked deficit in their ability to orient to an elevated sound source. Further behavioral testing indicated that this deficit is not the secondary result of an attentional or peripheral motor deficit. Although the present results do not prove that the reflexive deficit is strictly auditory in nature, the deficit is notable in that it is the only one yet known to result from a lesion of the dorsal cochlear nucleus or its central projections.

Structural magnetic resonance image averaging in schizophrenia.

OBJECTIVE: Intersubject averaging of structural magnetic resonance (MR) images has been infrequently used as a means to study group differences in cerebral structure throughout the brain. In the present study, the authors used linear intersubject averaging of structural MR images to evaluate the validity and utility of this technique and to extend previous research, conducted using a different approach to image averaging, in which reduction in thalamic size and abnormalities in perithalamic white matter tracts in the brains of schizophrenic patients were reported by Andreasen et al. METHOD: A 1.5-T MR scanner was used to obtain high-resolution, whole brain T1-weighted structural MR images for an age-matched sample of 25 schizophrenic patients and 25 normal control subjects. A "bounding box" procedure was used to create a single "averaged" brain for the schizophrenic group and for the control group. Differences in signal intensity between the two average brains were examined on a pixel-wise basis through use of one-tailed effect size maps. RESULTS: Effect size maps revealed widespread patchy signal intensity differences between the two groups in both cortical and periventricular areas, including major white matter tracts. The signal intensity differences were consistent with cortical thinning/sulcal widening and ventricular enlargement. No differences were found within thalamus or in immediately surrounding white matter. Effect size maps for differences (schizophrenic minus normal subjects) had only small values. CONCLUSIONS: These results are consistent with diffuse structural brain abnormalities of both gray and white matter in schizophrenic populations such as the one in this study.

Childhood-onset schizophrenia. Progressive ventricular change during adolescence.

BACKGROUND: There is controversy about progression in brain abnormalities in later-onset schizophrenia. This study looked for more striking progression in brain abnormalities during adolescence in a chronically ill, treatment-refractory sample of patients with childhood-onset schizophrenia who had had more prepsychotic developmental disturbance, but clinical and neurobiological characteristics similar to those of patients with treatment-refractory adult-onset schizophrenia who have poor outcome. METHODS: Anatomic brain magnetic resonance images were obtained for 16 children and adolescents with onset of schizophrenia by 12 years of age and 24 temporally yoked, age- and sex-matched healthy controls. Subjects were scanned on initial admission and rescanned after 2 years with the identical equipment and measurement methods. RESULTS: Childhood schizophrenics showed a significantly greater increase in ventricular volume than did controls, for whom ventricles did not increase significantly (analysis of variance, diagnosis x time, F = 16.1, P < .001). A significant decrease in midsagittal thalamic area was also seen for the schizophrenics (P = .03), which was unchanged at rescan for controls. These differential brain changes correlated significantly with each other and tended to be predicted by both prepsychotic developmental abnormality (Premorbid Assessment Scale, P = .06) and Brief Psychiatric Rating Scale at follow-up (P = .07). CONCLUSIONS: More consistent progressive ventricular enlargement was seen during adolescence for this childhood-onset sample than has been reported for adult-onset populations. The brain imaging results support other clinical data showing both early and late deviations in brain development for at least this rare subgroup of treatment-refractory, very-early-onset schizophrenic patients.

MRI of the brain in neurologically healthy middle-aged and elderly individuals.

Our purpose was to document the MRI appearances of the brain in healthy middle-aged to elderly subjects. T2- and proton density-weighted axial slices were obtained in 61 volunteers, 30-86 years of age. After visual inspection, signal intensities of brain structures were measured on T2-weighted images. Age-related changes became increasingly apparent after age 50. The main findings were that signal intensity of the white matter increased concomitantly with widening of the cerebrospinal fluid spaces; that basal ganglia remained stable; that high-signal foci in white matter increased in number and size after the age of 50 years; that periventricular high-signal foci were constant after the age of 65 years. Our visual impression of a decrease in signal intensity of the central grey matter with age seems to be mistaken. Pathological processes should be suspected if periventricular foci are found in middle-aged or young subjects.

Brain anatomic magnetic resonance imaging in childhood-onset schizophrenia.

BACKGROUND: Early-onset schizophrenia (first psychotic symptoms by age 12 years) has been the subject of a small number of studies, and its biological continuity with later-onset disorder has not been established. In this study quantitative anatomic brain magnetic resonance images of children and adolescents with early-onset schizophrenia were compared with those of matched controls. Brain abnormalities in childhood-onset schizophrenia were examined in relation to those reported for later-onset schizophrenics. METHODS: Anatomic brain magnetic resonance imaging scans were obtained for 21 patients (mean +/- SD age, 14.6 +/- 2.1 years; range, 10 to 18 years) with childhood-onset schizophrenia (13 males, eight females) and 33 age-, sex-, height-, and weight-matched normal controls. Quantitative measurements were obtained for the cerebrum, anterior frontal region, lateral ventricles, thalamus, caudate, putamen, and globus pallidus. RESULTS: Total cerebral volume and midsagittal thalamic area were smaller in the patients (analysis of variance, P = .002, and analysis of covariance, P = .03, respectively); the caudate, putamen, and globus pallidus were larger in the patients (analysis of covariance, P = .05, P = .007, and P < .001, respectively); and the lateral ventricles tended to be larger in the patients (analysis of covariance, P = .06). Globus pallidus enlargement correlated with neuroleptic exposure and with age of onset of psychosis. The magnitude of abnormalities compared with controls was similar to that reported in adult studies, although there was a trend toward relatively smaller cerebral volumes for the childhood-onset group compared with controls. CONCLUSION: Brain anatomic abnormalities in childhood-onset schizophrenia are similar to those reported for adult populations, indicating overall continuity between these rare childhood cases and the adult schizophrenia populations.

[The anatomy and the MRI anatomy of the interhemispheric cerebral commissures]. / Anatomie et anatomie IRM des commissures inter-hémisphériques cérébrales.

Correlation of myelin-stained or cryotomic sections of human brain with inversion-recovery MR images can display the cerebral commissures as white-matter tracts (in hypersignal on MRI), crossing the mid-line. MRI shows routinely in three orthogonal planes a) the corpus callosum stretched above the supra-tentorial ventricles, it's four portions (rostrum, genu, body and splenium) and connections with the Deep Grey Nuclei b) the fornix, intralimbic commissure joining anteriorly the mammillary bodies (through it's columns) to the alveus posteriorly and inferiorly (via it's two crura), arcing around the thalamus and lying over the hippocampus and the dentate gyrus as shown on the frontal sections c) the anterior commissure, white-matter tract connecting the two temporal lobes. In axial view, the anterior commissure has the shape of bicycle handlebars, coursing posteriorly, inferiorly and laterally behind the head of the caudate nucleus and passes into the lateral nucleus of the globus pallidus into the inferior and middle temporal gyri. Because the anterior commissure is easily recognisable in all planes, it's appears to be a important landmark for identification of the lateral and medial nuclei of the globus pallidus on axial and sagittal planes d) at least, the posterior commissure, anterior margin of the pineal region, closely related to the superior colliculi, acquire a major importance in the AC-PC line delineation becoming a reference landmark for stereotatical procedures.

Immunocytochemical localization of the catecholamine-synthesizing enzymes, tyrosine hydroxylase and dopamine-beta-hydroxylase, in the hypothalamus of cattle.

Immunocytochemical staining for the presence of catecholamine synthesizing enzymes, tyrosine hydroxylase and dopamine beta-hydroxylase, was used to characterize the regional distribution of catecholaminergic neurons in the hypothalamus and adjacent areas of domestic cattle, Bos taurus. In steers, heifers and cows, tyrosine hydroxylase-immunoreactive perikarya was located throughout periventricular regions of the third cerebral ventricle, in both anterior and retrochiasmatic divisions of the supraoptic nucleus, suprachiasmatic nucleus, and ventral and dorsolateral regions of the paraventricular nucleus, dorsal hypothalamus, ventrolateral aspects of the arcuate nucleus, along the ventral hypothalamic surface between the median eminence and optic tract, and in the posterior hypothalamus. Immunostained perikarya ranged from small (10-20 microns, parvicellular) to large (30-50 microns, magnocellular) and were of multiple shapes: round, triangular, fusiform or multipolar, often with 2-5 processes of branched arborization. There were no dopamine-beta-hydroxylase immunoreactive perikarya observed within the hypothalamus and adjacent structures. However, both tyrosine hydroxylase and dopamine-beta-hydroxylase immunoreactive fibers and punctate varicosities were observed throughout regions of tyrosine hydroxylase immunoreactivity perikarya. Generally, the location and pattern of hypothalamic tyrosine hydroxylase immunoreactivity and dopamine-beta-hydroxylase immunoreactive were similar to those reported for most other large brain mammalian species, however, there were several differences with commonly used small laboratory animals. These included intense tyrosine hydroxylase immunoreactivity of perikarya within the retrochiasmatic division of the supraoptic nucleus (ventral A15 region), the absence of tyrosine hydroxylase immunoreactive perikarya below the anterior commissure or within the bed nucleus of stria terminalis (absence of the dorsal A15 region), an abundance of tyrosine hydroxylase immunoreactive perikarya within the ependymal layer of the median eminence, heavy innervation of the arcuate nucleus with dopamine-beta-hydroxylase immunoreactive fibers and varicosities, and the paucity of dopamine-beta-hydroxylase immunoreactive throughout the median eminence.