Postmortem cryosectioning as an anatomic reference for human brain mapping.

This study examined the densitometric and topographic detail of high resolution 3D digital postmortem cryosectioned brain images. Anatomic image data and histology from cryosectioned human brain were compared to in vivo MRI for the ability to delineate neuroanatomic structure. 3D surface reconstructions in the Talairach and Tournoux atlas ("Co-planar stereotaxic atlas of the human brain", Thieme, New York, 1988) coordinate system enabled morphometric comparisons for a representative sample of neuroanatomic structures.

A molecular analysis of vesicular amine transport.

To package classical neurotransmitters into vesicles so that their release can be regulated by activity, neuronal cells express a set of specific vesicular transport proteins. We have used selection in MPP+ to clone the cDNAs encoding two vesicular monoamine transporters, the first members of this novel gene family that now also includes the vesicular transporter for acetylcholine. The sequences show similarity to several bacterial antibiotic resistance proteins, further supporting a role in detoxification and possibly Parkinson's disease.

Migraine as a cause of sudden hearing loss.

Sudden hearing loss is common, but unexplained in many cases. Although usually attributed to a viral infection of the inner ear in most patients, the abrupt onset of the hearing loss in many patients argues against a viral etiology. We present 13 cases of unexplained sudden hearing loss who meet the diagnostic criteria for migraine.

Identification of residues involved in substrate recognition by a vesicular monoamine transporter.

To identify the residues involved in substrate recognition by recently cloned vesicular monoamine transporters (VMAT1 and VMAT2), we have mutagenized the conserved residues in a cytoplasmic loop between transmembrane domains two and three of VMAT2. Although studies of related bacterial antibiotic resistance proteins indicate an important functional role for this region, we found no effect of these mutations on VMAT2 activity. However, replacement of aspartate 33 in the first predicted transmembrane domain with an asparagine (D33N) eliminates transport.

The linear vestibulo-ocular reflex in normal subjects and patients with vestibular and cerebellar lesions.

We measured the horizontal linear vestibulo-ocular reflex (LVOR) in normal human subjects and patients with abnormal angular vestibulo-ocular reflexes (AVOR) and abnormal smooth pursuit. Eye movements were induced by sinusoidal linear acceleration along the interaural axis (0.8 Hz, 0.

Functional increases in cerebral blood volume over somatosensory cortex.

We have examined the relationship between cerebral blood volume (CBV) and electrophysiology over primary somatosensory cortex (S-I) in the rat. We did this by comparing the spatial characteristics and time course of activity-related changes in plasma fluorescence, intrinsic optical reflectance signals, and single unit electrophysiology in S-I to identical stimuli. S-Is of urethane-anesthetized male Sprague-Dawley rats were exposed, and fluorescent Texas Red dextran dye (MW 70,000) was administered intravenously.

Persistent direction-changing positional nystagmus: another variant of benign positional nystagmus?

Positional nystagmus that does not fatigue, persists as long as the position is held, and changes direction in different head positions has typically been attributed to central vestibular lesions. We recently studied three patients who presented with positional nystagmus having these features but almost certainly of benign peripheral origin. All three had an initial history typical of benign positional vertigo and, in two, the persistent direction-changing positional nystagmus occurred after the patient underwent a maneuver to remove debris from the posterior semicircular canal.

Recent advances in clinical neurotology.

In recent years, owing to significant technological developments and an increased number of investigators entering the field, there have been spectacular advances in our understanding of the basic anatomy and physiology of the vestibular system. Unfortunately, these advances in basic science are slow to impact the clinical management of patients. We have selected a few important advances in clinical neurotology that have impacted the diagnosis and treatment of patients with vestibular disorders.

Posturography and balance problems in older people.

Objective: To determine which measurements and test conditions on posturography are most useful for identifying balance problems in older people.

Subjects: Two samples of 70 community-dwelling older subjects (> 75 years). One group (controls) considered their balance normal for their age, and the other (patients) complained of imbalance.

Channels of the corpus callosum. Evidence from simple reaction times to lateralized flashes in the normal and the split brain.

We studied 75 normal subjects and three commissurotomized patients using unimanual simple reaction times to lateralized flashes as a behavioural estimate of interhemispheric transmission time. Three different versions of the paradigm were performed: (i) the basic task; (ii) a motor task, with an increased complexity of the motor response; and (iii) a visual task, with an increased complexity of the visual stimulus presentation. We tested two hypotheses.

A 3D digital map of rat brain.

A three dimensional (3D) computerized map of rat brain anatomy created with digital imaging techniques is described. Six male Sprague-Dawley rats, weighing 270-320 g, were used in the generation of this atlas. Their heads were frozen, and closely spaced cryosectional images were digitally captured.

Callosal transmission time before and after partial commissurotomy.

Interhemispheric transmission time was measured in a patient, before and after partial commissurotomy sparing the splenium of the corpus callosum, using a simple reaction time paradigm with unimanual responses to lateralized flashes at 4 degrees and 8 degrees of eccentricity. Post-operative transfer time was longer than pre-operative transfer time at 8 degrees but not at 4 degrees of eccentricity. These data do not support the notion that the callosal transfer time is always faster through motor rather than visual fibers.

Preferential localization of a vesicular monoamine transporter to dense core vesicles in PC12 cells.

Neurons and endocrine cells have two types of secretory vesicle that undergo regulated exocytosis. Large dense core vesicles (LDCVs) store neural peptides whereas small clear synaptic vesicles store classical neurotransmitters such as acetylcholine, gamma-aminobutyric acid (GABA), glycine, and glutamate. However, monoamines differ from other classical transmitters and have been reported to appear in both LDCVs and smaller vesicles.

High-resolution anatomy from in situ human brain.

We have generated a spatially accurate, high-resolution three-dimensional (3D) volume of brain anatomy from cryosectioned whole human head. The head of a female cadaver was cryosectioned on a heavy duty cryomacrotome (PMV, Stockholm Sweden) modified for quantitative digital image capture. Serial images (1024(2), 24-bit) were captured directly from the cryoplaned specimen blockface in 500-micron intervals and reconstructed to a 3D data volume.

Postmortem anatomy from cryosectioned whole human brain.

A system of histologic and digital processing protocols are presented for the acquisition of high-resolution digital imagery from postmortem cryosectioned whole human brain and head for computer-based 3-dimensional (3D) representation and visualization. We designed and evaluated several protocols for optimal preparation of frozen specimens including fixation, decalcification, cryoprotection, freezing and sectioning procedures. High-resolution (1024(2) pixel) serial images were captured directly from the cryoplaned blockface using an integrated color digital camera and fiber optic illumination system mounted over a modified cryomacrotome.

Quality of life of epilepsy surgery patients as compared with outpatients with hypertension, diabetes, heart disease, and/or depressive symptoms.

Health-related quality of life (HRQOL) of 166 adults who had previously undergone surgical treatment for intractable epilepsy was compared with that of outpatients with hypertension, diabetes, heart disease, and/or depressive symptoms. Eight self-reported HRQOL domains were evaluated and compared by the RAND 36-Item Health Survey 1.0: emotional well-being, social function, role limitations due to emotional problems, energy/fatigue, pain, role limitations due to physical problems, physical function, and general health perceptions.

Comparison of static and dynamic posturography in young and older normal people.

Objective: To measure sway velocity during static and dynamic posturography in "normal" older people and to determine which tests best distinguish young from older subjects.

Subjects: A sample of 30 young (18-39 years) and 82 community-dwelling older (> 75 years) subjects who reported normal balance underwent a battery of balance tests.

Measurements: Velocity and frequency of sway, Tinetti gait and balance score, self-reported fear of falling and number of falls.

The chromaffin granule and synaptic vesicle amine transporters differ in substrate recognition and sensitivity to inhibitors.

Classical studies using bovine chromaffin granules have defined the physiologic and pharmacologic properties of the vesicular amine transporter that packages monoamine transmitters into intracellular vesicles for subsequent regulated release. The recent isolation of two distinct but closely related cDNA clones encoding vesicular amine transport suggests that the activity expressed in the brain (synaptic vesicle amine transporter or SVAT) may differ significantly from the previously described adrenal gland activity (chromaffin granule amine transporter or CGAT). A direct comparison of the two transporters now shows that SVAT has a higher affinity than CGAT for monoamine substrates, in particular for histamine.

The neuroanatomy of depression.

Findings from computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and single photon emission computed tomography (SPECT) studies of patients with depression suggest that this mood disorder is associated with regional brain dysfunction. The various elements of depression--dysphoria, anhedonia, helplessness, and sad affect--are all closely associated with changes in cerebral blood flow and/or metabolism in the frontal-temporal cortex and caudate nucleus. A compelling convergence of information from psychiatric and neurologic investigations indicates that depression is mediated by a restricted set of brain structures.

Neural degeneration and the transport of neurotransmitters.

A number of neurodegenerative diseases selectively affect distinct neuronal populations, but the mechanisms responsible for selective cell vulnerability have generally remained unclear. The toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reproduces the selective degeneration of dopaminergic neurons in the substantia nigra characteristic of Parkinson's disease. The plasma membrane dopamine transporter mediates this selective toxicity through accumulation of the active metabolite N-methyl-4-phenylpyridinium (MPP+).

BCL-2 blocks glutamate toxicity in neural cell lines.

Glutamate has been shown, at high concentrations (5-10 mM), to lead to death in cells of the pheochromocytoma cell line PC12. We report that similar concentrations of glutamate also kill immortalized central neural cell lines, and that the expression of the proto-oncogene bcl-2 in these cell lines blocks glutamate neurotoxicity. Potassium chloride (25 mM) also protects a cerebellar neuronal cell line, but not PC12 cells, from glutamate toxicity.

Lymphokine induction of rat microglia multinucleated giant cell formation.

Multinucleated giant cell formation (MNGC) occurs in central nervous system AIDS. The mechanism of fusion of microglia in these cases is unknown. We investigated the ability of lymphokines to induce fusion and found that interleukin-3 (IL-3), interleukin-4 (IL-4), gamma interferon (gamma-IFN), and granulocyte-macrophage colony stimulating factor (GM-CSF) induced MNGC formation in cultures of rat microglia in vitro.

Progressive frontal dysfunction.

A number of causes of progressive mental impairment show a preponderance of frontal lobe symptoms. It is proposed that these disorders can be subdivided into primary and secondary frontal dementias, based on the symptomatology and the site of major pathological disruption. An anatomical explanation, based on variations in cortical and subcortical influences, aids in understanding the clinical differences.