Gert Andersson

Climbing fiber microzones in cerebellar vermis and their projection to different groups of cells in the lateral vestibular nucleus

Summary1.The projections from one of the paths (b-VF-SOCP) in the ventral spino-olivocerebellar system to the cortical b-zone located in the lateral part of the anterior lobe vermis and to the lateral vestibular nucleus (LVN) have been studied in cats with the spinal cord transected at C3 sparing only the contralateral ventral funiculus. The projection to the b-zone was studied by recording climbing fiber responses in single Purkinje cells on stimulation of limb nerves. The projections to the LVN, direct through climbing fiber collaterals and indirect through Purkinje cells, were studied by recording EPSPs and IPSPs in LVN neurons.2.The Purkinje cells in the b-zone were arbitrarily divided into five groups with different inputs and occupying different microzones each with a width of about 200 μm. On passing medially across the b-zone the microzones had the following input characteristics: 1. activation exclusively from hindlimb nerves, 2. short-latency activation from hindlimb and long-latency activation from forelimb nerves, 3. short-latency activation from hindlimb and forelimb nerves, 4. short-latency activation from forelimb and long-latency activation from hindlimb nerves, and 5. activation exclusively from forelimb nerves.3.The five microzones projected to different groups of LVN neurons which occurred intermingled throughout the nucleus. The LVN neurons inhibited from a certain microzone were activated by the collaterals of the climbing fibers projecting to that microzone.4.The organization of the spino-olivo-cerebello-vestibulo-spinal path is discussed. It is suggested that the microzone and collection of subcortical neurons represent the basic computational unit of the cerebellum.

Projections to lateral vestibular nucleus from cerebellar climbing fiber zones.

Summary1.The olivary projections to the lateral vestibular nucleus (LVN), direct and excitatory through climbing fiber collaterals and indirect and inhibitory through climbing fiber activated Purkinje cells, were investigated in cats with the spinal cord transected at C3 sparing only the contralateral ventral funiculus. In this preparation all spinocerebellar paths are interrupted except the ventral spino-olivocerebellar paths (VF-SOCPs). Three VF-SOCPs responding with different latencies and receptive fields on limb nerve stimulation project to different sagittal zones in the anterior lobe vermis: the a-zone medially and the b-zone laterally in the vermis and the c1-zone in the extreme lateral part of the vermis and the medial part of the pars intermedia.2.The EPSPs evoked through climbing fiber collaterals and the following IPSPs evoked through climbing fiber activated Purkinje cells were recorded intracellularly from LVN neurons on limb nerve stimulation. Simultaneously the climbing fiber responses evoked in Purkinje cells located in the a-, b- and c1-zones were recorded as positive potentials from the cerebellar surface.3.Three groups of LVN neurons were distinguished: X neurons (about 20 %) which did not receive excitation or inhibition from the olivary paths, aCF neurons (about 5%) which received excitation and inhibition from the olivary path projecting to the a-zone, and bCF neurons (about 75 %) which received excitation and inhibition from the olivary path projecting to the b-zone. No LVN neurons were related to the c1-zone.4.The aCF and bCF neurons occurred intermingled throughout the LVN. The X neurons occurred predominantly in its ventral part.5.The findings are discussed in relation to a hypothesis of cerebellar organization.

Evidence for a GABA-mediated cerebellar inhibition of the inferior olive in the cat

Summary1. Climbing fibres were activated by peripheral nerve stimulation at ‘high’ frequencies (>3 Hz) for 15–25 s and then at 0.9 Hz for about 1 min. The high frequency activation induced a post-conditioning inhibition, lasting up to about 1 min, of climbing fibre responses recorded from the cerebellar surface. 2. Electrolytic lesions were made in the superior cerebellar peduncle (brachium conjunctivum). After the lesion, the post-conditioning inhibition was completely eliminated. 3. Injections of the GABA-receptor blocker bicuculline methiodide into the inferior olive reversibly blocked the post-conditioning inhibition. 4. The results support the hypothesis proposed by Andersson and Hesslow (1987a), that post-conditioning inhibition is mediated by a GABA-ergic interposito-olivary pathway.

Long-term outcomes five years after selective dorsal rhizotomy

BackgroundSelective dorsal rhizotomy (SDR) is a well accepted neurosurgical procedure performed for the relief of spasticity interfering with motor function in children with spastic cerebral palsy (CP). The goal is to improve function, but long-term outcome studies are rare. The aims of this study were to evaluate long-term functional outcomes, safety and side effects during five postoperative years in all children with diplegia undergoing SDR combined with physiotherapy.MethodsThis study group consisted of 35 children, consecutively operated, with spastic diplegia, of which 26 were Gross Motor Function Classification System (GMFCS) levels III–V. Mean age was 4.5 years (range 2.5–6.6). They were all assessed by the same multidisciplinary team at pre- and at 6, 12, 18 months, 3 and 5 years postoperatively. Clinical and demographic data, complications and number of rootlets cut were prospectively registered. Deep tendon reflexes and muscle tone were examined, the latter graded with the modified Ashworth scale. Passive range of motion (PROM) was measured with a goniometer. Motor function was classified according to the GMFCS and measured with the Gross Motor Function Measure (GMFM-88) and derived into GMFM-66. Parents opinions about the childrens performance of skills and activities and the amount of caregiver assistance were measured with Pediatric Evaluation Disability Inventory (PEDI).ResultsThe mean proportion of rootlets cut in S2-L2 was 40%. Muscle tone was immediately reduced in adductors, hamstrings and dorsiflexors (p < 0.001) with no recurrence of spasticity over the 5 years. For GMFCS-subgroups I–II, III and IV–V significant improvements during the five years were seen in PROM for hip abduction, popliteal angle and ankle dorsiflexion (p = 0.001), capacity of gross motor function (GMFM) (p = 0.001), performance of functional skills and independence in self-care and mobility (PEDI) (p = 0.001).ConclusionSDR is a safe and effective method for reducing spasticity permanently without major negative side effects. In combination with physiotherapy, in a group of carefully selected and systematically followed young children with spastic diplegia, it provides lasting functional benefits over a period of at least five years postoperatively.

Clinical measurements of proprioception, muscle strength and laxity in relation to function in the ACL-injured knee.

A knee injury with anterior cruciate ligament (ACL) rupture may cause deficits in proprioception, increased laxity and decreased muscle strength. Although it may be common knowledge that these factors affect knee function, only a few studies have been performed where this has been investigated in the clinical situation, and the results are not conclusive. The purpose of this study was therefore to investigate how and to what extent proprioception, laxity and strength affect knee joint function and evaluate if the methods commonly used for estimating these factors clinically seem to be relevant. The study encompassed 36 patients with ACL deficiency. A single-leg hop test for distance and subjective rating of knee function were defined as dependent variables and analyzed separately in stepwise linear regression models where proprioception, knee joint laxity, hamstrings and quadriceps strength, age and sex were defined as independent variables. Higher threshold values (poorer proprioception), increased side-to-side difference of anterior laxity and poorer strength significantly predicted shorter length of the hop test. Higher rating of subjective function corresponded to female gender, lesser side-to-side difference of anterior laxity and better proprioception.

Spread of synaptic activity along parallel fibres in cat cerebellar anterior lobe

Summary1. Mossy fibre evoked activity in the cerebellar cortex elicited by peripheral electrical stimulation was studied in chloralose anesthetized cats. The distribution of intracortical field potentials in the C3 and D zones was mapped in order to determine if there is a spread of synaptic activity outside the mossy fibre termination area. This area was identified by the presence of short latency synaptic field potentials in the granular layer. 2. Molecular layer field potentials were recorded up to 1.5 mm outside the mossy fibre termination area. The latencies of these potentials increased with increasing distance from the mossy fibre termination area, corresponding to a conduction velocity of about 0.4 m/s. 3. Recordings from Purkinje cells, within and outside the mossy fibre termination area, revealed an increase of simple spike activity at latencies corresponding to those of the field potentials in the same location. 4. From the spatial and temporal characteristics of the evoked activity, it is concluded that a mossy fibre input results in spread of synaptic activity along the parallel fibres. 5. The findings are discussed in relation to the recently discovered microzonal organization of the C3 zone. It is proposed that the organization of this zone offers a possibility for the control of muscle synergies, each synergy being represented by a mossy fibre input and the specific set of microzones activated by this input via the parallel fibres.

Wartenberg pendulum test: objective quantification of muscle tone in children with spastic diplegia undergoing selective dorsal rhizotomy.

The aim of this study was to investigate the reliability and sensitivity of the Wartenberg pendulum test for quantification of muscle tone in young children with spastic diplegia undergoing selective dorsal rhizotomy (SDR). Fourteen non‐disabled children (mean age of 5.5 years, age range 2.3 to 8.8 years, one female and one male in each year) were tested twice. Twenty children with spastic diplegia (12 males, eight females; mean age of 4.3 years, age range 2.5 to 6.3 years) consecutively selected for SDR, were assessed before and 6 months after SDR. Parameters of the pendulum test: R2, R1, maximal velocity, and swing time were correlated with clinical assessments for spasticity (modified Ash worth scale, quadriceps reflex) and measurements of gross motor function: the Gross Motor Function Classification System and the Gross Motor Function Measure. The Wartenberg pendulum test was found to be an objective and sensitive method for quantifying spasticity in knee extensor muscles in children as young as 2.5 years old. The method was responsive to changes after SDR. The only correlation with clinical measurements of spasticity was between the R2 ratio and the quadriceps reflex. Swing time was the most reliable and sensitive variable; it showed a weak correlation with measurements for gross motor function.

Spinal, trigeminal, and cortical climbing fibre paths to the lateral vermis of the cerebellar anterior lobe in the cat

SummaryThe spinal, trigeminal and cortical climbing fibre projection to the lateral vermis of the cerebellar anterior lobe in the cat has been investigated. The b zone, which occupies a one mm wide band in the lateral vermis, receives a somatotopically arranged input. Successively more rostral segments (tail, hindlimb, thorax, forelimb and trigeminal nerves) project to successively more medial microzones. The b zone receives an input through each of three spino-olivocerebellar paths (SOCPs) ascending in the ventral, dorsal and dorsolateral funiculi (VF, DF and DLF). In the b zone, the hindlimb input is bilateral through the VF-SOCP and ipsilateral through the DF- and DLF-SOCPs. The forelimb input is bilateral through the VF-SOCP, ipsilateral through the DLF-SOCP and lacking from the DF-SOCP. The trigeminal input is bilateral. Medial to the b zone in lobule V is the x zone, which receives an input from the ipsilateral forelimb through the DF- and DLF-SOCPs. The climbing fibres to the x zone are collaterals of the climbing fibres projecting to the c1 zone in the pars intermedia and paramedian lobule. The climbing fibre input from the cerebral sensorimotor cortex to the lateral vermis matches the spinal input. The lateral and medial parts of the b zone receive a bilateral input from hind- and forelimb cortical areas, respectively. The x zone receives an input from the contralateral forelimb area. The functional significance of the converging paths is discussed.

Knee joint proprioception in ACL-deficient knees is related to cartilage injury, laxity and age: a retrospective study of 54 patients.

BACKGROUND ACL-deficient patients have been found to have proprioceptive defects, but the cause of these defects has not been identified nor has the relationship between proprioception and subjective function, laxity, activity level and age been adequately studied. PATIENTS AND METHODS Therefore, we analyzed proprioception, defined as the threshold to detect a slow passive motion (TTDPM), in relation to activity level, laxity, meniscal injuries, collateral ligament injuries, cartilage injuries, age and subjective function in 54 patients with a previous ACL rupture. We used multiple pair-wise correlation analyses, followed by a stepwise linear regression model. RESULTS We found that poorer proprioception was related to lateral cartilage lesions, increased laxity and older age while a high activity level before injury was related with better proprioception after injury. The results also suggest a relation between proprioception and subjective knee function. INTERPRETATION Anatomical injuy classification may need to be considered when discussing proprioceptive ability in patients with an ACL injury, laxity is related to proprioception and proprioception may decrease with age.

Activity of Purkinje cells and interpositus neurones during and after periods of high frequency climbing fibre activation in the cat.

SummaryThe activity of cerebellar Purkinje cells and interpositus neurones was recorded during and after periods of high frequency (2.5–7.5 Hz) climbing fibre activation in barbiturate-anaesthetized cats. 1. During the high frequency conditioning stimulation, the Purkinje cell simple spike (SS) firing was initially silenced in all zones studied. After a few seconds, the SS reappeared and the frequency increased to well above that of the control level after approximately 10 s. Thereafter, the SS rate started to decline so that, after 15–20 s, the Purkinje cells fired no more SS. This SS silence lasted up to 60 s, whether or not the stimulation was continued. 2. The Purkinje cells responded with a complex spike (CS) to every stimulus. If the high-frequency stimulation lasted for at least 15 s, the spontaneous CS discharge of the Purkinje cells in the c1, c2, and c3 zones was suppressed after the conditioning stimulation had ended. This suppression lasted for approximately the same length of time as the SS silence. In the b zone, however, no CS suppression was observed. 3. Interpositus neurones displayed an increased discharge rate after periods of conditioning stimulation, thus displaying a mirror image of the Purkinje cell SS firing. 4. The behaviour of the neurones agrees well with the behaviour predicted by an hypothesis of the olivo-cerebello-olivary loop (Andersson and Hesslow 1987). 5. The results suggest that the cerebello-olivary projection is topographically organized and matches the microzonal organization in the olivo-cerebellar projection.