The olivocerebellar projection studied with the method of retrograde axonal transport of horseradish peroxidase. V. The projections to the flocculonodular lobe and the paraflocculus in the rabbit.

HRP was injected in the flocculonodular lobe and the paraflocculus in the rabbit to determine the areas of the inferior olive which project onto these cerebellar regions. Following injections in the flocculus labeled cells occurred in the dorsal cap and the rostralmost tip of the medial accessory olive. Following injections in the nodulus labeled cells were likewise found in the dorsal cap, but in addition in the rostralmost part of the dorsomedial cell column and the adjoining part of the medial accessory olive. Injections in the dorsal paraflocculus gave rise to labeling in the rostrolateral part of the medial accessory olive, while injections in the ventral paraflocculus resulted in labeling in the principal olive, mainly in the lateral part of the ventral lamella. Injections in the lateral third of the dentate nucleus gave rise to labeling mainly in the dorsal lamella of the principal olive. The results are discussed with reference to those obtained by previous authors. There are both similarities and discrepancies. It appears from what is known of afferents from areas mediating visual impulses to the inferior olive that the olivary areas projecting onto the flocculonodular lobe, and possibly the dorsal paraflocculus, may mediate visual impulses to these lobules.

The olivocerebellar projection in the cat studied with the method of retrograde axonal transport of horseradish peroxidase. III. The projection to the vermal visual area.

Horseradish peroxidase (HRP) was injected separately in one of the cerebellar lobules VI, VIIA, VIIB, VIIIA or VIIIB (together corresponding to the vermal visual area) in 17 cats. After 1-3 days the distribution of labeled cells in the inferior olive was mapped. In spite of some overlapping it is clear that the various lobules of the vermal visual area receive fibers from separate parts of a horseshoeshaped region in the caudal half of the contralateral medial accessory olive (fig. 5C). The projection area of lobule VIIA is found caudomedially and overlapping with the area supplying lobule VIIB. This in addition receives a few fibers from the nucleus beta. Fibers terminating in lobule VIIIA arise caudolaterally as do fibers destined for lobule VIIIB. A central part of the total projection area projects to lobule VI. Following injections leading to a similar extent of cortical staining in lobules VI, VII or VIII the projection of labeled cells in the corresponding projection areas differ markedly. In the area of lobule VII apparently all cells are labeled, in the area of lobule VI the density of labeled cells is considerably less, and in that of lobule VIII there are rather few labeled cells. In a few cases with widespread staining of the cerebellar visual area there was spreading of HRP to the nucleus fastigii. The projection to this form the olive was therefore investigated to avoid erroneous conclusions. In the discussion it is pointed out that on most points our findings agree fairly well with the results of studies of the olivocerebellar projection undertaken with other methods (studies of retrograde cellular changes, electrophysiological methods). No support for a longitudinal subdivision of lobules VI-VIII was found. Studies of the available literature indicate that the areas in the medial accessory olive projecting onto lobules VI-VIII probably do not receive direct afferents from regions which are known to be concerned in the transmission of visually evoked impulses. Fibers to the olive from the superior colliculus appear to pass to the nucleus beta only. This projects mainly to the uvula, to a little extent only to lobule VII. However, it may be imagined that visual impulses may reach the vermal visual area via the inferior olive by way of intercalated neurons, for example in the mesencephalic RF. Major contingents of afferents to the olivary regions projecting onto the vermal area come from the spinal cord, the motor cortex and the periaqueductal gray.

The olivocerebellar projection in the cat studied with the method of retrograde axonal transport of horseradish peroxidase.

The distribution of labeled cells in the inferior olive of the cat has been mapped following injections of small amounts of horseradish perosidase in the paramedian lobule of the cerebellum. The distribution of labeled cells was plotted in drawings of approximately serial transverse sections. The findings in each case were transferred to a standard diagram of the olive to facilitate comparison of cases. Previous studies of the distribution of retrograde cell loss in the inferior olive following cerebellar lesions (Brodal, '40b) showed that fibers ending in the paramedian lobule come from the caudal part of the ventral lamella of the principla olive. This was confirmed with the peroxidase method, but in addition three other separate and well circumscribed area of the olive showed labeling: one in the dorsal accessory olive, another in the rostral part of the medial accessory olive, a third in the caudal part of the dorsal lamella of the principal olive (fig. 7). There is some degree of topical arrangement within the projection of each of these olivary areas to the paramedian lobule. It is particularly striking that the projection areas of the caudal one-third of the lobule are different from and overlap only little with those of the orstral two-thirds. On account of diffusion of the injected perosidase solution in the folia it could not be decided whether the different olivary areas project to particular longitudinal zones in the paramedian lobule. The main findings can be correlated with the physiological observations of Armstrong et al. ('74). Some of the "paramedian" olivary areas are labeled also following peroxidase injections in other cerebellar parts, among them the nuclei interpositus anterior and posterior. The findings are compatible with the notion that olivocerebellar fibers branch to supply more than one cerebellar region. It is confirmed that the olivocerebellar projection, including that of the nuclei, is almost completely crossed. In the discussion it is emphasized that afferents from several sources converge on all four olivary regions projecting onto the paramedian lobule. The olivocerebellar projection obviously allows for divergence as well as convergence of impulses from the olive to the cerebellum. For further insight into the anatomical organization of the inferior olive, the entire olivocerebellar projection has to be mapped with the peroxidase methods, and further studies of the afferents to the olive are needed. In such studies, as well as in physiological ones, it is essential that findings are described with meticulous reference to the topography of the olivary subdivisions.

The pontocerebellar projection onto the paramedian lobule in the cat: an experimental study with the use of horseradish peroxidase as a tracer.

Horseradish peroxidase (HRP) was injected into cerebellar cortex of the paramedian lobule in 12 cats, and the ensuing distribution of labeled cells in the pontine nuclei was mapped in some detail. The cells in the pontine gray which give origin to fibers to the paramedian lobule lie together, in part in groups, and in part in columns. The columns are situated both medial and ventrolateral to the peduncle, as well as in the dorsolateral pontine nucleus. The projection is bilateral with a clearcut contralateral preponderance, except in the lateralmost region in the dorsolateral nucleus, which projects mainly ipsilaterally. The column medial to the peduncle projects in a topographical pattern to the paramedian lobule. The dorsal part of this column projects to the rostral folia of the paramedian lobule, while successively more ventral parts in the column project to more caudal paramedian lobules. Within the other columns only a faint sign of a topographical organization is found. The location of the pontine columns projecting onto the paramedian lobule largely corresponds to the pontine terminal areas of fibers from the sensory cerebral cortex (SmI and SmII). The corresponding topography in these parts of the corticopontine and pontocerebellar pathways is suitable for a somatotopical impulse transmission from the sensory cortex to the paramedian lobule, in agreement with the results of physiological investigations. Furthermore, a correlation of the pontine areas projecting onto the paramedian lobule with the terminal areas of pontine afferents shows that the pons may be a relay station in mediating influences from other parts of the cortex (MsI, visual and acoustic), the cerebellar nuclei and the colliculi to the paramedian lobule.

The olivocerebellar projections to the flocculus and paraflocculus in the cat, compared to those in the rabbit. A study using horseradish peroxidase as a tracer.

The projections from the inferior olive to the flocculus and paraflocculus in the cat have been mapped by means of the method of retrograde axonal transport of horseradish peroxidase. The findings show that the afferents to the flocculus are derived from the dorsal cap, ventrolateral outgrowth, the principal olive (the caudal parts of the ventral and dorsal lamella) and from the rostral part of the medial accessory olive. The fibres to the paraflocculus come from the caudal part of the principal and from the rostral part of the medial accessory olive. Details in the projections are seen from Figs. 1 and 2. Concerning some points the findings are at variance with those made in the rabbit by Hoddevik and Brodal, and suggest that there are species differences hitherto not known.

The reticulovestibular projection in the cat. An experimental study with silver impregnation methods.

The distribution of degeneration in the vestibular nuclei (VN) has been studied in transversely cut sections from 9 cats with stereotaxically performed lesions in the main reticular formation (RF) of the brain stem (Nauta of Fink and Heimer method). No projection was found from the mesencephalic reticular formation (R.mes.) and nucleus reticularis ventralis (R.v.). However, the reticular nuclei gigantocellularis (R.gc.), parvocellularis (R.p.c.) and pontis oralis (R.p.o.) were found to project bilaterally onto the 4 main vestibular nuclei with an ipsilateral overweight. By far the greates contribution comes from the R.gc. and R.p.c. In cases with R.gc. lesions some degeneration was found in the small cell groups x and f. The latter is also supplied from the R.p.c. The distribution of degeneration within the vestibular complex is rather diffuse, but a certain pattern can be discovered. After R.p.c. lesions the maximal terminal field in the VN is found within the superior nucleus, while the lateral and medial nuclei are preferred sites of termination of fibers from R.gc. and R.p.c. The projections of the R.gc. and the R.p.c. may be more different than appears from our findings since lesions of one of them will most likely have affected some ascending or descending fibers emanating from the other. Since the areas of RF projecting to VN receive afferents from many sources, these sources have possibilities to act on the VN even if they do not possess direct connections with this nuclear complex. These possibilities should be remembered in physiological studies of responses in the VN following stimulation of many parts of the CNS.

The pontine projection to the cerebellar vermal visual area studied by means of the retrograde axonal transport of horseradish peroxidase.

Following injections of horseradish peroxidase (HRP) in cerbellar vermal lobules VI, VIIA and B, VIIA and B in the cat, the distribution of labeled cells in the pontine nuclei was mapped in drawings of serial transverse and horizontal sections. The labeled pontine cells are distributed in 4 largely longitudinal columns, situated in the dorsolateral, peduncular, lateral and paramedian pontine nucleus (referred to as columns A, B, C and D, respectively). The majority of afferents to the vermal, visual areas come from colums A and B. To some extent cells projecting to the various sublobules have their preferential location within each column (Fig. 5). The majority of the fibers end in lobule VII. Available data from the literature show that only columns A, D and rostral part of B may be involved in the transmission of visual impulses to the vermal area, since these columns receive afferents from the superior colliculus, the lateral geniculate body and the visual cortex, respectively. The route via the superior colliculus-dorsolateral nucleus appears to be quantitatively the most important. As judged from data on fiber connections, impulses from various sources (inferior colliculus, cerebellar nuclei and "non-visual" parts of the cerebral cortex) are transmitted to certain parts of the 4 columns. The functional importance of this convergence and some general features in the organization of the pons are discussed.

The reticulocerebellar projection in the cat as studied with retrograde transport of horseradish peroxidase.

Injections of horseradish peroxidase into the various parts of the cerebellar cortex and the cerebellar nuclei in the cat result in labelled cells within the reticular formation proper. All the reticular nuclei (with the exception of the reticular formation of the mesencephalon) send fibres to the cerebellum. The highest number of labelled neurons after cerebellar injections is found in the caudal reticular formation, especially within nucleus reticularis ventralis, nucleus reticularis lateralis and nucleus reticularis gigantocellularis. Another region for an accumulation of labelled cells is the rostral part of nucleus reticularis pontis caudalis. Except for the paraflocculus, all cerebellar cortical areas and all cerebellar nuclei receive afferents from one or more of the nuclei within the reticular formation proper, but the largest number of labelled neurons is observed in cases with injections including the intermediate-lateral part of lobulus simplex and the adjacent areas of the anterior lobe and crus I. the projection is bilateral with an ipsilateral preponderance (the cerebellar nuclei appear to receive a higher number of fibres from the contralateral side). Cells of all sizes are labelled, but labelled giant cells are found only after large cortical injections.

The cerebellar projection from the raphe nuclei in the cat as studied with the method of retrograde transport of horseradish peroxidase.

Following injections of horseradish peroxidase (HRP) in the cerebellar cortex and nuclei of the cat, the distribution of labeled cells in the raphe nuclei was mapped. The findings confirm those made previously in studies of retrograde cell degeneration following cerebellar ablations (Brodal et al., 1960a), and in addition reveal new details in the projection of the raphe nuclei onto the cerebellar cortex and nuclei. All the raphe nuclei except nucleus linearis intermedius and nucleus linearis rostralis project onto the cerebellar cortex. The nuclei raphe obscurus and pontis contribute the greatest number of afferents to the cerebellum. With the exception of lobule VI which probably is the recipient of a weak projection, all parts of the cerebellar cortex receive afferents from the raphe nuclei. The heaviest projection is to the vermis of lobules VIIA and X, and to crus II. The afferents to the cerebellar nuclei are few in number (Tables 2-6). The observations indicate that each raphe neuron probably projects to more than one terminal site in the cerebellum. The findings are discussed with reference to other efferent and afferent studies of the raphe nuclei. All these studies indicate that the raphe nuclei have widespread efferent and afferent connections, making them capable to participate in a variety of regulatory functions.

Afferent connections to the abducent nucleus in the cat.

The afferent connections to the abducent nucleus in the cat were studied by means of retrograde transport of WGA-HRP after implantations of the tracer in crystalline form. Retrogradely labelled cells were found bilaterally in the medial and descending vestibular nuclei, mainly in their ventral and medial portions, in the rostral part of the ipsilateral gigantocellular reticular nucleus, in the medial part of the contralateral caudal pontine reticular nucleus and bilaterally in the oculomotor nucleus, mainly in its dorsolateral division. Some labelled cells were also found bilaterally in the mesencephalic reticular formation, the periaqueductal grey and the nucleus of the trapezoid body.

["Silent" areas of the brain--a challenge in family practice]. / "Stumme" områder i hjernen--en utfordring i allmennpraksis.

Based on two medical histories found among complaints dealt with by the Norwegian Board of Health the author points out the main symptoms of frontal or temporal lobe failure. Following a history of three weeks one of the patients died as a result of an overlooked cerebral abscess. During the history three different doctors had made wrong diagnostic suggestions, mainly because of the coincidence of an influenza epidemic in the neighbourhood. The other patient died from a cerebral tumour. In his history epilepsy was the main symptom for many months. This diagnosis was overlooked because the doctor suggested that the patient had a high alcohol consumption.

[Acetazolamide--are there reasons for its revival in antiepileptic treatment?]. / Acetazolamid--verdt en renessanse i epilepsibehandlingen?

BACKGROUND: Since 1950 the carbonic anhydrase inhibitor acetazolamide has been used as an antiepileptic drug. Because of its tolerance developing properties, acetazolamide has probably been bypassed by the new antiepileptic drugs on the market. However, when taken for 14 day periods with one week's stop in between, acetazolamide is still of value in the treatment of epilepsy. MATERIAL AND METHODS: The paper discusses acetazolamide and its present use in antiepileptic treatment in the light of existing internal control and quality assurance requirements in the medical services. RESULTS: Irrespective og type of seizure, about 90% of patients have an initial reliable effect from acetazolamide, though it is uncertain how long the effect will last after repeated periods of use. As an additional drug, acetazolamide may be particularly well suited for women with menses-related seizures. INTERPRETATION: Acetazolamide may be the drug of choice when drug interaction is a problem, when rapid onset of effect is wanted, or when an additional drug is needed for a short period of time only.

The pontine projection to the flocculonodular lobe and the paraflocculus studied by means of retrograde axonal transport of horseradish peroxidase in the rabbit.

The occurrence and distribution of labeled cells in the pontine nuclei were mapped following injections of small amounts of horseradish peroxidase (0.05-0.5 microliter, 50% suspension) in the flocculus, nodulus and the dorsal and ventral paraflocculus in adult albino rabbits. While no labeled cells were found in the pontine nuclei following injections in the nodulus, some were present following injections in the flocculus and a great number following injections in the paraflocculus. The projections onto the flocculus and paraflocculus are precisely organized. Following injections in the paraflocculus labeled neurons are arranged in four columns (E and G in the paramedian pontine nucleus, F in the peduncular and H in the dorsolateral nucleus). Following injections in the ventral paraflocculus labeled cells are present only in parts of column E and F, while columns G and H and parts of E and F project onto the dorsal paraflocculus. Following injections in the flocculus labeled cells occur in the rostral part of column E only. A comparison between the sites of termination of pontine afferents and the areas giving origin to floccular and parafloccular fibers shows that only few fibers mediating visual impulses end in these pontine areas, while they receive numerous fibers from gyrus cinguli and areas 18 and 19 of the cerebral cortex.

The pontine projection onto longitudinal zones of the paramedian lobule in the cat.

The distribution of labeled cells in the pontine nuclei was studied following microinjections of horseradish peroxidase into three longitudinal zones in the paramedian lobule in the cat. Labeled cells were only found when the staining of the cerebellar cortex included the granular layer. The labeled cells were present contralateral to the injection site in the cases with the smallest injections, in the others there was a bilateral distribution with a contralateral preponderance. The labeled cells lie concentrated in three groups medially, ventrally, and laterally to the peduncle. No indication of a different projection from these three groups to the three longitudinal paramedian zones was found, although in the same material a zonal projection exists for the climbing fibers from various parts of the inferior olive to the same cerebellar lobule (Brodal and Walberg, 1977).

[Chronic low back pain in 40-year olds in 12 Norwegian counties]. / Kroniske korsryggssmerter hos 40-åringer i 12 norske fylker.

In this study, a questionnaire and a short interview were used to estimate the prevalence of chronic low back pain alone and low back pain together with other musculo-skeletal pains among 40-year-old women and men in 12 Norwegian counties (a total of 67,338 persons). On average 2.4% of men and 1.7% of women had only chronic low back pain, while 5.7% of men and 9.2% of women in addition had other pains as well. Persons with low back pain only were approximately equally distributed across the counties. Greater variations across the counties and between the sexes were found in persons with additional pain. The duration of the pain did not vary significantly between the sexes or across the counties, but the duration was on average two years longer in cases of multi-cause pain. Reduced capacity for work because of pain was approximately equally distributed between the sexes and the groups. More women than men were unable to do their daily work. About one third in both groups (more men than women) had been absent from work because of pain during the last year. More women than men in both groups received national insurance benefits. Persons with only low back pains were approximately equally represented across all levels of education and regardless of marital status, while people with multi-cause pain were overrepresented among those with low levels of education and among the divorced.

The pontocerebellar projection of the uvula in the cat.

The occurrence of retrogradely labeled cells in the pontine nuclei was mapped following injections of 0.3-0.4 microliter of a horseradish peroxidase suspension (50% weight/volume) into the uvula (lob. IX of Larsell) in the cat. The uvula was found to receive afferents from three pontine cell collections. One of these is situated in the paramedian pontine nucleus close to the midline. It forms a fairly distinctly outlined longitudinal column of cells and is present at all levels of the pons except most rostrally and caudally. Another group, in the dorsolateral and lateral pontine nuclei, extends as a somewhat shorter cell column in the longitudinal direction. The third region consists of cells within the rostral part of the peduncular nucleus in its dorsomedial region. The pontine projection to the uvula is bilateral, with some preponderance of crossed connections. The projection to the uvula is organized according to the pattern determined previously for pontine projections to other parts of the cerebellum. A single lobule or part of its receives afferents from more than one cell group in the pons. The projecting cells are most often arranged in longitudinal columns. Correlations with data on the termination of afferents to the pons permit some conclusions regarding the sources of information reaching the uvula via the pons. Main sources seem to be the superior and inferior colliculi, the intracerebellar nuclei and the sensorimotor cortices.

Cerebellar afferent projections from the perihypoglossal nuclei: an experimental study with the method of retrograde axonal transport of horseradish peroxidase.

Details of cerebellar afferent projections from the perihypoglossal nuclei were studied in the cat by means of retrograde axonal transport of horseradish peroxidase (HRP). Labeled cells were observed bilaterally (with a preponderance ipsilaterally) in nuclei intercalatus and praepositus hypoglossi following injections in various folia of the entire vermis, paraflocculus, flocculus, fastigial nucleus, and the nucleus interpositus anterior and posterior. Relatively high densities of labeled cells were found in nucleus intercalatus following injections in the anterior part of the vermis, whereas labeled cells in nucleus praepositus hypoglossi were found more frequently following injections in the posterior part of the vermis. Labeled cells in the nucleus of Roller were found only following injections in the anterior lobe vermis, posterior vermal lobules VI and VII, in the flocculus and in the nucleus interpositus anterior. No labeled cells could be detected in the three subdivisions of the perihypoglossal nuclei following HRP injections in crus I, crus II, paramedian lobule, and lateral cerebellar nucleus. The distribution of the HRP positive cells indicated the presence of a topographically organized projection from certain regions of the perihypoglossal nuclei to different parts of the cerebellum. The afferent and efferent connections of the perihypoglossal nuclei in relation to a functional role in eye and head movements are discussed.

A note on the method of retrograde transport of horseradish peroxidase as a tool in studies of afferent cerebellar connections, particularly those from the inferior olive; with comments on the orthograde transport in Purkinje cell axons.

1. Injections of horseradish peroxidase (HRP) suspension were made in the cerebellar cortex of cats (most often the paramedian lobule). The staining of the cerebellar cortex and the ensuing labeling of neurons in the inferior olive were studied in experiments with variations of concentration of HRP, amounts of fluid injected, survival time and age of the animals. Light microscopical studies were supplemented with electron microscopical observations. The folded cerebellar cortex offers particular difficulties with regard to obtaining a predictable extent of stained tissue, and the spreading of the fluid within the cortex shows great variations even with the same amounts and concentrations of HRP suspension. Diffusion of fluid appears to occur most easily within the molecular layer. Often there are unstained parts of folia between stained parts. Staining of the cortex is barely visible after 7 days, but appreciable shrinking of the stained area does not appear to occur until after 4 days. 2. The first signs of labeling of olivary neurons are seen after 5-10 hours, after 7 days there are no labeled cells. The rate of retrograde transport in olivocerebellar fibers is calculated to be between 50 and 100 mm/day. Labeling of cells appears to require staining of the molecular layer of its projection areas in the cerebellum. 3. For studies of the olivocerebellar projection survival times of 2-3 days and injections of 0.5 mul of a 50% HRP suspension seem in general to be well suited. Best results are obtained with animals weighing 1-3 kg. There is a clearcut correlation between the site of staining of the cortex of a particular part of the cerebellum and the site(s) and extension of olivary area(s) containing labeled cells. 4. Anterograde transport in axons of Purkinje cells has been observed. Electron microscopically the axons of these fibers contain HRP labeled tubules and vesicles as do their terminal boutons in the nuclei. 5. In cases where the injected fluid has spread to the cerebellar nuclei, localized parts contain neurons which are labeled as are the cells in the injected cerebellar cortex.