Peripheral Tremor Research Articles

Brief Submotor-Threshold Electrical Stimulation Applied Synchronously Over Wrist Flexor and Extensor Muscles does Not Suppress Essential Tremor, Independent of Stimulation Frequency.

Electrical stimulation of muscles below motoneuron threshold has shown potential as a low-cost and minimally invasive treatment for Essential Tremor (ET). Prior studies have stimulated wrist flexor and extensor muscles synchronously with diverging results, calling for further investigation. Also, prior studies have only used a narrow range of stimulation parameters, so stimulation parameters have not been optimized. Our purpose was to further investigate synchronous submotor stimulation and identify the effect of stimulation frequency on tremor suppression. We quantified the effect of brief, synchronous stimulation at 15 different frequencies from 10-150 Hz applied over wrist flexors and extensors on both tremor power and frequency in 20 ET patients. We compared tremor power and frequency from hand acceleration and sEMG between pre-, per-, and post-stimulation phases. Our stimulation paradigm did not result in significant tremor suppression or tremor frequency changes at any tested stimulation frequency, showing no significant interaction between phase and stimulation frequency for tremor power measured by either hand acceleration (p = 0.69) or sEMG (p = 0.07). Additionally, the effect of phase interacting with stimulation frequency on tremor frequency was statistically insignificant for acceleration (p = 0.64) and sEMG (p = 0.37). We conclude that brief synchronous submotor-threshold stimulation does not reduce tremor in ET patients, independent of stimulation frequency (from 10 to 150 Hz). Our results are consistent with the hypothesis that brief submotor-threshold stimulation suppresses tremor via reciprocal inhibition, which requires asynchronous stimulation. In contrast, it is hypothesized that synchronous stimulation might require longer stimulation durations to affect supraspinal tremor networks. We studied the effects of synchronous submotor electrical stimulation over wrist flexor and extensor muscles on Essential Tremor. Our results indicate that suppressing tremor with brief synchronous stimulation is ineffective. Based on recently hypothesized mechanisms of peripheral tremor suppression, we hypothesize that asynchronous stimulation or long-duration synchronous stimulation are more effective approaches to peripheral tremor suppression.

Essential Tremor accentuates the pattern of tremor-band coherence between upper-limb muscles.

Although Essential Tremor is one of the most common movement disorders, current treatment options are relatively limited. Peripheral tremor suppression methods have shown potential, but we do not currently know which muscles are most responsible for patients' tremor, making it difficult to optimize suppression methods. The purpose of this study was to quantify the relationships between the tremorogenic activity in muscles throughout the upper limb. Muscle activity was recorded from the 15 major superficial upper-limb muscles in 24 subjects with Essential Tremor while they held various postures or made upper-limb movements. We calculated the coherence in the tremor band (4-12 Hz) between the activity of all muscle pairs and the time-varying phase difference between sufficiently coherent muscle pairs. Overall, the observed pattern somewhat mirrored functional relationships: agonistic muscle pairs were most coherent and in phase, whereas antagonist and unrelated muscle pairs exhibited less coherence and were either consistently in phase, consistently antiphase, consistently out of phase (unrelated pairs only), or else inconsistent. Patients exhibited significantly more coherence than control subjects (p<0.001) in the vast majority of muscle pairs (95 out of 105). Furthermore, differences between patients and controls were most pronounced among agonists; thus, the coherence pattern existing in control subjects was accentuated in patients with ET. We conclude that tremor-band activity is broadly distributed among the muscles of the upper limb, challenging efforts to determine which muscles are most responsible for a patient's tremor.

Distribution of tremorogenic activity among the major superficial muscles of the upper limb in persons with Essential tremor

ObjectivePeripheral tremor suppression has the potential to reduce tremor, but we do not currently know where best to intervene. The purpose of this study was to characterize the distribution of tremorogenic activity among upper-limb muscles. MethodsSurface electromyography was recorded from the 15 major superficial muscles of the upper limb while 25 patients with Essential Tremor performed postural and kinetic tasks. We defined tremorogenic activity as power in the tremor band (4–8 Hz) and determined the distribution of this power among muscles. ResultsThe distribution varied considerably between patients (mean r = 0.58), but on average, the greatest power was found in the anterior deltoid and extensor carpi ulnaris muscles. Other muscles with high power included the extensor carpi radialis, pectoralis major, lateral deltoid, and brachialis muscles. This distribution was similar (mean r ≥ 0.88) for postural and kinetic tremor, various limb configurations, repetitions, and patient characteristics (sex, tremor severity, age of onset, and duration). ConclusionsWe identified a rough pattern in which muscles opposing gravity appeared to have the highest tremor-band power; we hypothesize that the distribution of tremorogenic muscle activity depends in part on the distribution of voluntary activity required by the task. SignificanceUnderstanding which muscles exhibit the most tremorogenic activity is one of the steps in the pursuit of optimizing peripheral tremor suppression.

Essential tremor amplitude modulation by median nerve stimulation

Essential tremor is a common neurological disorder, characterised by involuntary shaking of a limb. Patients are usually treated using medications which have limited effects on tremor and may cause side-effects. Surgical therapies are effective in reducing essential tremor, however, the invasive nature of these therapies together with the high cost, greatly limit the number of patients benefiting from them. Non-invasive therapies have gained increasing traction to meet this clinical need. Here, we test a non-invasive and closed-loop electrical stimulation paradigm which tracks peripheral tremor and targets thalamic afferents to modulate the central oscillators underlying tremor. To this end, 9 patients had electrical stimulation delivered to the median nerve locked to different phases of tremor. Peripheral stimulation induced a subtle but significant modulation in five out of nine patients—this modulation consisted mainly of amplification rather than suppression of tremor amplitude. Modulatory effects of stimulation were more pronounced when patient’s tremor was spontaneously weaker at stimulation onset, when significant modulation became more frequent amongst subjects. This data suggests that for selected individuals, a more sophisticated control policy entailing an online estimate of both tremor phase and amplitude, should be considered in further explorations of the treatment potential of tremor phase-locked peripheral stimulation.

Symposium 2: Movement Disorders SY2.1. Evaluation of Tremor

Tremor is defined as an involuntary, rhythmic (regularly recurrent) and oscillatory (rotating around a central plane) movement of the body part. The evaluation of tremor should begin with careful history taking and a focused clinical examination on tremor phenomenology and associated neurological signs. The first step of the approach is to exclude tremor mimics such as myoclonus, clonus or other hyperkinetic movements. The second step is to carefully evaluate clinical features and establish whether the tremor is isolated or combined with other neurological problems and the predominant tremor is at rest or action. Tremor can be classified into syndromes depending on the characteristics (e.g. activation of tremor, distribution of tremor) and prominent additional signs. The common tremor syndromes during action are essential tremor, enhanced physiologic tremor, dystonic tremor, drug-induced tremor, cerebellar tremor, rubral tremor, and orthostatic tremor while the common tremor syndromes at rest are parkinsonian tremor. A detailed tremor history and neurological examination are usually enough for the clinical evaluation of tremor syndromes. However, the clinical presentations are sometimes complex and electrophysiologic investigations can be helpful in making the diagnosis of tremor subtypes. The basic neurophysiologic test is a multi-channel surface EMG combined with accelerometry to assess the distribution of tremor, tremor frequency, and amplitude during various types of activation of tremor, the effect of loading and distraction on tremor frequency and amplitude. The characteristics of central tremor syndromes are more stable tremor frequency and less influenced by loading compared to peripheral tremor syndromes. The peak tremor frequency can be overlapped among tremor subtypes but a unique tremor frequency can be found in some syndrome such as orthostatic tremor, cerebellar tremor and rubral tremor. The specific neurophysiologic procedures including distractibility and entrainment are sensitive and specific for functional tremors. Recently, more advanced neurophysiologic tests have emerged. There is a promising role of intermuscular coherence analysis in the differential diagnosis of tremor subtypes. Evaluation of tremor based on clinical and neurophysiological features are important, leading to the appropriate diagnosis and treatment.

Distribution of tremor among the major degrees of freedom of the upper limb in subjects with Essential Tremor

ObjectiveAlthough Essential Tremor is one of the most common movement disorders, we do not currently know which muscles are most responsible for tremor. Determining this requires multiple steps, one of which is characterizing the distribution of tremor among the degrees of freedom (DOF) of the upper limb. MethodsUpper-limb motion was recorded while 22 subjects with ET performed postural and kinetic tasks involving a variety of limb configurations. We calculated the mean distribution of tremor among the seven DOF from the shoulder to the wrist, as well as the effect of limb configuration, repetition, and subject characteristics (sex, tremor onset, duration, and severity) on the distribution. ResultsOn average, kinetic tremor was greatest in forearm pronation-supination and wrist flexion–extension, intermediate in shoulder internal-external rotation and wrist radial-ulnar deviation and then shoulder flexion–extension and elbow flexion–extension, and least in shoulder abduction–adduction. The average distribution of postural tremor was similar except for forearm pronation-supination, which played a smaller role than in kinetic tremor. Limb configuration and subject characteristics did significantly affect tremor, but practically only in forearm pronation-supination and wrist flexion–extension. There were no significant differences between repetitions, indicating that the distribution was consistent over the duration of the experiment. ConclusionsThis paper presents a thorough characterization of tremor distribution from the shoulder to the wrist. SignificanceUnderstanding which DOF exhibit the most tremor may lead to more targeted peripheral tremor suppression.

The response of the central and peripheral tremor component to octanoic acid in patients with essential tremor

ObjectiveTo investigate the effect of octanoic acid (OA) on the peripheral component of tremor, as well as OA’s differential effects on the central and peripheral tremor component in essential tremor (ET) patients. MethodsWe analyzed postural tremor accelerometry data from a double-blind placebo-controlled cross-over study evaluating the effect of 4 mg/kg OA in ET. The weighted condition was used to identify tremor power for both the central and peripheral tremor components. Exploratory non-parametric statistical analyses were used to describe the relation between the central and peripheral component of tremor power. ResultsA peripheral tremor component was identified in 4 out of 18 subjects. Tremor power was reduced after OA administration in both the central and the peripheral tremor component. There was a positive correlation of tremor power between the central and peripheral component, both after placebo and OA. ConclusionsWhen present, the peripheral component was closely related to the central tremor component. We hypothesize that the magnitude of the peripheral mechanical component of tremor is determined by that of the central component. SignificanceBoth central and peripheral component of tremor are reduced after OA, with the central component providing the energy driving the peripheral component.

The central oscillatory network of orthostatic tremor

Orthostatic tremor (OT) is a movement disorder of the legs and trunk that is present in the standing position but typically absent when sitting. The pathological central network involved in orthostatic tremor is still unknown. In this study we analyzed 15 patients with simultaneous high-resolution electroencephalography and electromyography recording to assess corticomuscular coherence. In 1 patient we were able to simultaneously record the local field potential in the ventrolateral thalamus and electroencephalography. Dynamic imaging of coherent source analysis was used to find the sources in the brain that are coherent with the peripheral tremor signal. When standing, the network for the tremor frequency consisted of unilateral activation in the primary motor leg area, supplementary motor area, primary sensory cortex, two prefrontal/premotor sources, thalamus, and cerebellum for the whole 30-second segment recorded. The source coherence dynamics for the primary leg area and the thalamic source signals with the tibialis anterior muscle showed that they were highly coherent for the whole 30 seconds for the contralateral side but markedly decreased after 15 seconds for the ipsilateral side. The source signal and the recorded thalamus signal followed the same time frequency dynamics of coherence in 1 patient. The corticomuscular interaction in OT follows a consistent pattern with an initially bilateral pattern and then a segregated unilateral pattern after 15 seconds. This may add to the feeling of unsteadiness. It also makes the thalamus unlikely as the main source of orthostatic tremor.

振戦の病態生理

Tremor is a rhythmic involuntary movement of any body parts. Some peripheral and central mechanisms can produce it. The former includes peripheral mechanical oscillations and oscillations due to spinal reflexes. The latter includes central oscillations originated from some central pacemakers or network loops through cerebellum, basal ganglia or others.Weight loading on a body part is one method for differentiation between the peripheral and central mechanisms. In peripheral tremor, the weight load usually changes the tremor frequency. In contrast, it is not affected by the load in the central tremor. Both mechanisms relate to produce essential tremor and enhanced physiological tremor.Basal ganglia, sensory-motor cortex, cerebellum, red nucleus and inferior olive nucleus could be the central pacemakers or involved in the central loops for tremor.The facilitation and inhibition imbalance within a pacemaker or imbalance between feed-forward and feedback regulations within central loops may generate some rhythms.

Essential Tremor After Ipsilateral Cerebellar Hemispherectomy: Support for the Thalamus as the Central Oscillator

Essential tremor is a long-recognized and common movement disorder, yet controversy still surrounds its pathophysiology. The olivo-cerebello-thalamo-cortical pathway has been implicated in the genesis of essential tremor, and the inferior olive has been considered the central oscillator driving the peripheral tremor. We present the case of a patient who developed essential tremor ipsilateral to cerebellar hemispherectomy and propose that the central oscillator in patients with essential tremor may not be the inferior olive in all cases, but rather the nucleus ventralis intermedius of the thalamus.

A peripheral tremor associated with intractable pain after traffic accident: case report

There are debates about whether peripherally induced movement disorders exist. We report a case of upper limb tremor induced by peripheral nerve injury. A 20-year-old male patient presented with pain and tremor of the left upper extremity, 2 days after a car accident. Magnetic resonance images of the brain and cervical spine were normal. His past medical history was unremarkable and there were no family members with symptoms of movement disorders. He suffered from an aggravating tremor for about 10 minutes, four to six times a day. We treated the patient with medication, epidural infusion, cervical nerve root block and trigger point injection of the trapezius muscle. The pain subsided 50% and the incidence of tremor attacks was reduced to once or twice a day. The role of peripheral trauma in the genesis of movement disorders has not been generally accepted. It is unclear whether peripheral trauma can induce dystonia and other movement disorders. It has been proposed that peripheral trauma can alter sensory input and induce cortical and subcortical reorganization that generates a movement disorder. Some studies provide evidence for central reorganization following peripheral injury.

Oscillatory Communication between Cerebral Areas Associated with Essential Tremor

With an estimated prevalence of about 5%, essential tremor (ET) is the most frequent movement disorder. Nevertheless, the pathophysiological mechanisms giving rise to this usually bilateral 5–9Hz action tremor which mostly affects the upper extremities are still largely unknown. There is accumulating evidence that ET is at least partly of central origin. Animal models suggest an involvement of the inferior olive. PET and fMRI studies showed activation in several brain areas including cerebellum, thalamus and primary motor cortex, and an EEG-EMG coherence study demonstrated involvement of the primary sensorimotor cortex. In addition, the effect of deep brain stimulation in the thalamus of patients suffering from essential tremor reduces the action tremor, pointing towards an important involvement of the thalamus in the generation or mediation of tremor. We studied 8 patients with essential tremor by recording simultaneously neural activity with a whole-scalp neuromagnetometer (MEG) and peripheral tremor activity with surface electrodes (EMG). Subjects performed an isometric contraction of the left forearm for a total duration of about four minutes with interleaved rest periods of 30 seconds. All subjects showed a tremor at a frequency of 5–7Hz. Tremor frequency and its first harmonic were clearly evident in power spectra of the EMG recordings. We used the localization technique DICS to identify cerebral areas with significant coherence to EMG at tremor frequency and its first harmonic. Coherence is a correlation measure in the frequency domain which is normalized between 0 and 1. All subjects showed significant coherence between EMG of the wrist extensor muscle and contralateral primary motor cortex. All but one subject showed significant coherence between EMG and ipsilateral cerebellum. Phase delays between cerebral areas and EMG at the tremor frequency and its first harmonic were computed and indicated the existence of both afferent and efferent components in the coupling. In a further step DICS was used to identify areas of significant cerebro-cerebral coherence. The analysis revealed a network of areas consisting of contralateral primary motor cortex, premotor cortex, thalamus, brainstem and ipsilateral cerebellum which showed strongest coupling at twice the tremor frequency. Partial coherence analysis excluded the possibility that one central driving oscillator simply entrains oscillations in these areas leading to spurious coherences. These results are consistent with the view that in ET patients a brainstem-cerebello-thalamo-premotor-motor cortical network shows oscillatory interactions which lead to a rhythmic modulation of muscle activity becoming apparent as tremor.

Model Based Development of Novel Deep Brain Stimulation Techniques

Pathological synchronization is a hallmark of several neurological diseases like Parkinson's disease (PD) or essential tremor [Alberts et al., Nature 1969; 221: 670; Nini et al., J Neurophys 1995; 74: 1800]. For example, a pacemaker-like population of neurons, which fires in a synchronized and periodical manner, provokes the Parkinsonian resting tremor [Alberts et al., Nature 1969; 221: 670]. In contrast, an uncorrelated, i.e., desynchronized firing pattern of these neuronal populations is characteristic in healthy subjects [Nini et al., J Neurophys 1995; 74: 1800]. In medically intractable patients, electrical deep brain stimulation (DBS) is administered via depth electrodes chronically implanted in the subthalamic nucleus of the thalamic ventralis intermedius nucleus [Benabid et al., Lancet 1991; 337: 403]. For that purpose, a permanent high-frequency (>100Hz) periodic pulse train stimulation is used. Up to now the mechanism of high-frequency DBS is not yet sufficiently understood [Benabid et al., Lancet 1991; 337: 403]. We initiated a model-based development of novel stimulation protocols to find milder and more effective DBS techniques [Tass, Phase Resetting in Medicine and Biology, Springer, 1999; Tass, Biol Cyb 2003; 89: 81]. In a first clinical study performed during electrode implantation, we have shown that the coordinated reset via multiple/several sites can suppress the peripheral tremor, even if the standard high-frequency DBS has no tremor suppressive effect at all [Tass et al., submitted (2004)]. Here we present a technique for the desynchronization of a strongly synchronized target population which we expect to be even more effective and milder. For this, delayed mean field potentials are administered at different sites within a neuronal population to establish a desynchronized state. According to detailed theoretical investigations and simulations, we expect the novel desynchronization technique to be considerably milder, to act in a demand-controlled way and to be simple in realization. We use a microscopic model of a neuronal population in a relevant target area to show that the method is robust and does not require time consuming calibration. It is suggested that the novel technique is used for deep brain stimulation in patients suffering from Parkinson's disease, essential tremor or epilepsy.

Delay estimation for cortico-peripheral relations

In neurophysiology, time delays between concurrently measured time series are usually estimated from the slope of a straight line fitted to the phase spectrum. We point out that this estimate is valid only in the case in which, one signal is a mere time-delayed copy of the other one. We present a procedure for delay estimation that applies to a much wider class of systems with nontrivial phase spectrum like for example lowpass filters. The procedure is based on the Hilbert transform relation between the phase of a linear system and its log gain. The Hilbert transform relation is nonlocal in frequency space, a fact that limits its applicability to experimental data. We explore these limits, and demonstrate that the method is applicable to neurophysiological time series. We present the successful application of the Hilbert transform behavior method to concurrently recorded epicortical brain activity and peripheral tremor. We point out and explain physiologically unreasonable delay estimates given by the traditional method. Finally, we discuss the assumptions underlying the applicability of the Hilbert transform method in the neuroscience context.

Synchronization tomography: Synchronization analysis of MEG current density solutions in patients with Parkinson's disease

Introdwtion The genesis of the parkinsonian resting tremor is not yet sufficiently understood. Using magnetoencephalography (MEG) and the magnetic field tomography (MIT) [l] Volkmann et al. [2] were able to localize cerebral activity that is time-locked to the EMG burst onset. Their results suggest that thalamic activity drives the supplementary motor area (SMA) and the premotor cortex (PMC), where both SMA and PMC drive the primary motor cortex (Ml). To analyze the dynamic interaction of cortical activty during epochs of tremor we applied our novel single-run synchronization analysis [3] directly to MEG signals measured in tremordominant PD patients [3]. In patients with alternating tremor we found pathological activity over motor areas in the 10 Hz range. This activity is 1:2 synchronized with the peripheral tremor activity (5 Hz range), whereas the different motor areas engaged in tremor generation are 1: 1 synchronized. The spatial resolution of this study was obvioulsy limited since no inverse modeling was involved. We here combine the two approaches to detect and localize both cortico-cortical and cortico-muscular synchronization processes with our novel synchronization tomography. Methods We simultaneously recorded MEG and EMG activity from 5 patients suffering from an early stage PD during periods of spontaneous tremor activity. MEG signals were recorded with the BTi Magnes 2500 whole-head system. Voxel by voxel we applied our single-run synchronization analysis [3] to the reconstructed cerebral current source density solutions obtained with the magnetic field tomography (MFI) [2]. Results We find a strong cortico-muscular synchronization between premotor areas (PMC, SMA) and sensorimotor areas (mainly Ml) on the one hand and the peripheral muscular activity on the other hand. In Patients with an alternating tremor the cortical activity is in the 10 Hz range, whereas in patients with a coactivation tremor it is in the 5 Hz range. Correspondingly, in patients with an alternating tremor we find a cortico-muscular 1:2 synchronization, and in patients with a coactivation tremor a cortico-muscular 1:l synchronization. The activity in the different motor areas engaged in tremor generation is 1:l synchronized. The strength of the cortico-muscular and cortico-cortical synchronization reflect the time course of the amplitude of the peripheral tremor.

Load dependence of simulated central tremor.

Previous studies have argued that tremors of central versus peripheral origin can be distinguished based on their load dependence: the frequency of peripheral tremor decreases when a weight is added to the tremulous limb, while the frequency of central tremors remains unchanged. The present study scrutinizes the latter statement. We simulated central tremor using a simple network of coupled neural oscillators, which receives proprioceptive feedback from the motor periphery. The network produced a self-sustained, stable oscillation. When the gain of proprioceptive feedback was high, oscillation frequency decreased in the presence of an inertial load. When the gain was low, the oscillation frequency was load independent. We conclude that load dependence is not an exclusive property of peripheral tremors but may be found in tremors of central origin as well. Therefore, the load test is not sufficient to reject a central tremor origin.

Dependence of peripheral tremor on mechanical perturbations: a modeling study.

The present study scrutinizes the popular view that tremors of central origin but not those of peripheral origin are largely resistant to mechanical perturbations. We explore the effects of perturbations in a well-established model of peripheral tremor and document that (a) tremor frequency can remain unchanged when spring or weight loads are added, (b) entrainment by external drives can be limited to drives of similar frequency, and (c) resetting of tremor phase by torque pulses can remain fractional. This resistance to mechanical perturbations arises in the model because peripheral neuromuscular dynamics act as a limit-cycle oscillator which, by its very nature, will absorb moderate changes to signals and parameters. We conclude from our study that resistance to mechanical perturbations is not an exclusive property of central tremors, but rather may also be found in peripheral tremors. Other criteria are therefore needed to distinguish between different origins of tremor.

Detection ofn:mPhase Locking from Noisy Data: Application to Magnetoencephalography

We use the concept of phase synchronization for the analysis of noisy nonstationary bivariate data. Phase synchronization is understood in a statistical sense as an existence of preferred values of the phase difference, and two techniques are proposed for a reliable detection of synchronous epochs. These methods are applied to magnetoencephalograms and records of muscle activity of a Parkinsonian patient. We reveal that the temporal evolution of the peripheral tremor rhythms directly reflects the time course of the synchronization of abnormal activity between cortical motor areas.

Assessment of the permissible exposure level to manganese in workers exposed to manganese dioxide dust.

The prevalence of neuropsychological and respiratory symptoms, lung ventilatory parameters, neurofunctional performances (visual reaction time, eye-hand coordination, hand steadiness, audioverbal short term memory), and several biological parameters (calcium, iron, luteinising hormone (LH), follicle stimulating hormone (FSH), and prolactin concentrations in serum, blood counts, manganese (Mn) concentration in blood and in urine) were examined in a group of workers (n = 92) exposed to MnO2 dust in a dry alkaline battery factory and a matched control group (n = 101). In the battery plant, the current exposure of the workers to airborne Mn was measured with personal samplers and amounted on average (geometric mean) to 215 and 948 micrograms Mn/m3 for respirable and total dust respectively. For each worker, the lifetime integrated exposure to respirable and total airborne Mn dust was also assessed. The geometric means of the Mn concentrations in blood (MnB) and in urine (MnU) were significantly higher in the Mn exposed group than in the control group (MnB 0.81 v 0.68 microgram/100 ml; MnU 0.84 v 0.09 microgram/g creatinine). On an individual basis, MnU and MnB were not related to various external exposure parameters (duration of exposure, current exposure, or lifetime integrated exposure to airborne Mn). On a group basis, a statistically significant association was found between MnU and current Mn concentrations in air. No appreciable difference between the exposed and the control workers was found with regard to the other biological measurements (calcium, LH, FSH, and prolactin in serum). Although the erythropoietic parameters and serum iron concentration were in the normal range for both groups, there was a statistically significant trend towards lower values in the Mn exposed workers. The prevalences of reported neuropsychological and respiratory symptoms, the lung function parameters, and the audioverbal short term memory scores did not differ between the control and exposed groups. The Mn workers, however, performed the other neurofunctional tests (visual reaction time, eye-hand coordination, hand steadiness) less satisfactorily than the control workers. For these tests, the prevalences of abnormal results were related to the lifetime integrated exposure to total and respirable Mn dust. On the basis of logistic regression analysis it may be inferred that an increased risk of peripheral tremor exists when the lifetime integrated exposure to Mn dust exceeds 3575 or 730 micrograms Mn/m3 x year for total and respirable dust respectively. The results clearly support a previous proposal by the authors to decrease the current time weighted average exposure to Mn dust.

Unit activity in human thalamic reticularis nucleus. I. Spontaneous activity

Microelectrode recording was carried out in the thalamic reticularis nucleus (Rt) during 51 stereotaxic operations performed in locally anesthetized dyskinetic patients. The spontaneous activity (SA) of 426 units was studied by means of computer processing techniques. Three types of unit (A, B, C) were shown to exist in Rt: with irregular low-frequency (0–10/sec) discharges (A type, 51%); bursting in short trains (10–30 msec) with unstable rhythmic pattern (2–5/sec; B type, 42%); presenting long duration (0.1–2 sec) high frequency bursts and relatively constant interburst silences (80–150 msec; C type, 7%). During short-term anesthesia A unit discharges disappeared; on the contrary the rhythmic bursts of B neurons were synchronized and presented a more stable frequency. The 3 types of cell were present in the whole Rt. However, a number of discharge characteristics (frequency, variation of rhythm) of A and B units changed significantly with the position of the cells in the Rt. No relationship was found between the frequencies of the rhythmic bursts and the parkinsonian tremor. With the use of a multiparametric statistical procedure, a relation was, however, found between the intensity of the peripheral tremor and the stability of the average frequency of the B type rhythmic bursts. The possible origins of rhythmic bursts of B and C neurons are discussed.