Tremor characteristics in the norm and in the diagnosis and treatment of parkinsonism

With the aid of tensotremorography, a voluntary effort was recorded and characteristics of involuntary and voluntary components of the hands' isometrically recorded efforts were studied. The revealed frequency ranges of the oscillations spectral density's changes corroborate existence of two suprasegmental systems of movements control, the systems being related to voluntary control and a current control of the efforts maintaining or preserving a posture. Results of cross-correlation analysis of the hands' efforts maintained under conditions of a visual feedback are demonstrated in norm and in central disorders of the movement control system.     

Sustained contraction at very low forces produces prominent supraspinal fatigue in human elbow flexor muscles.

During sustained maximal voluntary contractions (MVCs), most fatigue occurs within the muscle, but some occurs because voluntary activation of the muscle declines (central fatigue), and some of this reflects suboptimal output from the motor cortex (supraspinal fatigue). This study examines whether supraspinal fatigue occurs during a sustained submaximal contraction of 5% MVC. Eight subjects sustained an isometric elbow flexion of 5% MVC for 70 min. Brief MVCs were performed every 3 min, with stimulation of the motor point, motor cortex, and brachial plexus. Perceived effort and pain, elbow flexion torque, and surface EMGs from biceps and brachioradialis were recorded. During the sustained 5% contraction, perceived effort increased from 0.5 to 3.9 (out of 10), and elbow flexor EMG increased steadily by approximately 60-80%. Torque during brief MVCs fell to 72% of control values, while both the resting twitch and EMG declined progressively. Thus the sustained weak contraction caused fatigue, some of which was due to peripheral mechanisms. Voluntary activation measured by motor point and motor cortex stimulation methods fell to 90% and 80%, respectively. Thus some of the fatigue was central. Calculations based on the fall in voluntary activation measured with cortical stimulation indicate that about two-thirds of the fatigue was due to supraspinal mechanisms. Therefore, sustained performance of a very low-force contraction produces a progressive inability to drive the motor cortex optimally during brief MVCs. The effect of central fatigue on performance of the weak contraction is less clear, but it may contribute to the increase in perceived effort.     

Age-related changes in the activity of the human motor system

By analysis of parameters of isometric force recorded in healthy subjects from different age groups, amplitude and frequency changes in the integrated activity of motor system structures were shown to depend on voluntarily maintained isometric effort and its duration.     

Cortical Mechanisms of Central Fatigue and Sense of Effort

The purpose of this study was to investigate cortical mechanisms upstream to the corticospinal motor neuron that may be associated with central fatigue and sense of effort during and after a fatigue task. We used two different isometric finger abduction protocols to examine the effects of muscle activation and fatigue the right first dorsal interosseous (FDI) of 12 participants. One protocol was intended to assess the effects of muscle activation with minimal fatigue (control) and the other was intended to elicit central fatigue (fatigue). We hypothesized that high frequency repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area (SMA) would hasten recovery from central fatigue and offset a fatigue-induced increase in sense of effort by facilitating the primary motor cortex (M1). Constant force-sensation contractions were used to assess sense of effort associated with muscle contraction. Paired-pulse TMS was used to assess intracortical inhibition (ICI) and facilitation (ICF) in the active M1 and interhemispheric inhibitory (IHI) was assessed to determine if compensation occurs via the resting M1. These measures were made during and after the muscle contraction protocols. Corticospinal excitability progressively declined with fatigue in the active hemisphere. ICF increased at task failure and ICI was also reduced at task failure with no changes in IHI found. Although fatigue is associated with progressive reductions in corticospinal excitability, compensatory changes in inhibition and facilitation may act within, but not between hemispheres of the M1. rTMS of the SMA following fatigue enhanced recovery of maximal voluntary force and higher levels of ICF were associated with lower sense of effort following stimulation. rTMS of the SMA may have reduced the amount of upstream drive required to maintain motor output, thus contributing to a lower sense of effort and increased rate of recovery of maximal force.     

A dynamical model of muscle activation, fatigue, and recovery

A dynamical model is presented as a framework for muscle activation, fatigue, and recovery. By describing the effects of muscle fatigue and recovery in terms of two phenomenological parameters (F, R), we develop a set of dynamical equations to describe the behavior of muscles as a group of motor units activated by voluntary effort. This model provides a macroscopic view for understanding biophysical mechanisms of voluntary drive, fatigue effect, and recovery in stimulating, limiting, and modulating the force output from muscles. The model is investigated under the condition in which brain effort is assumed to be constant. Experimental validation of the model is performed by fitting force data measured from healthy human subjects during a 3-min sustained maximal voluntary handgrip contraction. The experimental results confirm a theoretical inference from the model regarding the possibility of maximal muscle force production, and suggest that only 97% of the true maximal force can be reached under maximal voluntary effort, assuming that all motor units can be recruited voluntarily. The effects of different motor unit types, time-dependent brain effort, sources of artifacts, and other factors that could affect the model are discussed. The applications of the model are also discussed.     

Using voluntary motor commands to inhibit involuntary arm movements

A hallmark of voluntary motor control is the ability to stop an ongoing movement. Is voluntary motor inhibition a general neural mechanism that can be focused on any movement, including involuntary movements, or is it mere termination of a positive voluntary motor command? The involuntary arm lift, or ‘floating arm trick’, is a distinctive long-lasting reflex of the deltoid muscle. We investigated how a voluntary motor network inhibits this form of involuntary motor control. Transcranial magnetic stimulation of the motor cortex during the floating arm trick produced a silent period in the reflexively contracting deltoid muscle, followed by a rebound of muscle activity. This pattern suggests a persistent generator of involuntary motor commands. Instructions to bring the arm down voluntarily reduced activity of deltoid muscle. When this voluntary effort was withdrawn, the involuntary arm lift resumed. Further, voluntary motor inhibition produced a strange illusion of physical resistance to bringing the arm down, as if ongoing involuntarily generated commands were located in a ‘sensory blind-spot’, inaccessible to conscious perception. Our results suggest that voluntary motor inhibition may be a specific neural function, distinct from absence of positive voluntary motor commands.     

A comparison of central aspects of fatigue in submaximal and maximal voluntary contractions.

Magnetic and electrical stimulation at different levels of the neuraxis show that supraspinal and spinal factors limit force production in maximal isometric efforts ("central fatigue"). In sustained maximal contractions, motoneurons become less responsive to synaptic input and descending drive becomes suboptimal. Exercise-induced activity in group III and IV muscle afferents acts supraspinally to limit motor cortical output but does not alter motor cortical responses to transcranial magnetic stimulation. "Central" and "peripheral" fatigue develop more slowly during submaximal exercise. In sustained submaximal contractions, central fatigue occurs in brief maximal efforts even with a weak ongoing contraction (<15% maximum). The presence of central fatigue when much of the available motor pathway is not engaged suggests that afferent inputs contribute to reduce voluntary activation. Small-diameter muscle afferents are likely to be activated by local activity even in sustained weak contractions. During such contractions, it is difficult to measure central fatigue, which is best demonstrated in maximal efforts. To show central fatigue in submaximal contractions, changes in motor unit firing and force output need to be characterized simultaneously. Increasing central drive recruits new motor units, but the way this occurs is likely to depend on properties of the motoneurons and the inputs they receive in the task. It is unclear whether such factors impair force production for a set level of descending drive and thus represent central fatigue. The best indication that central fatigue is important during submaximal tasks is the disproportionate increase in subjects' perceived effort when maintaining a low target force.     

Toward an objective interpretation of surface EMG patterns: a voluntary response index (VRI).

Individuals with incomplete spinal cord injuries (SCI) retain varying degrees of voluntary motor control. The complexity of the motor control system and the nature of the recording biophysics have inhibited efforts to develop objective measures of voluntary motor control. This paper proposes the definition and use of a voluntary response index (VRI) calculated from quantitative analysis of surface electromyographic (sEMG) data recorded during defined voluntary movement as a sensitive measure of voluntary motor control in such individuals. The VRI is comprised of two numeric values, one derived from the total muscle activity recorded for the voluntary motor task (magnitude), and the other from the sEMG distribution across the recorded muscles (similarity index (SI)). Calculated as a vector, the distribution of sEMG from the test subject is compared to the average vector calculated from sEMG recordings of the same motor task from 10 neurologically intact subjects in a protocol called brain motor control assessment (BMCA). To evaluate the stability of the VRI, a group of five healthy subjects were individually compared to the prototype, average healthy-subject vectors for all of the maneuvers. To evaluate the sensitivity of this method, the VRI was obtained from two SCI subjects participating in other research studies. One was undergoing supported treadmill ambulation training, and the other a controlled withdrawal of anti-spasticity medications. The supported treadmill training patient's VRI, calculated from pre- and post-training BMCA recordings, reflected the qualitative changes in sEMG patterns and functional improvement of motor control. The VRI of the patient followed by serial BMCA during medication withdrawal also reflected changes in the motor control as a result of changes in anti-spasticity medication. To validate this index for clinical use, serial studies using larger numbers of subjects with compromised motor control should be performed.     

Myoelectric manifestations of fatigue in voluntary and electrically elicited contractions

The time course of muscle fiber conduction velocity and surface myoelectric signal spectral (mean and median frequency of the power spectrum) and amplitude (average rectified and root-mean-square value) parameters was studied in 20 experiments on the tibialis anterior muscle of 10 healthy human subjects during sustained isometric voluntary or electrically elicited contractions. Voluntary contractions at 20% maximal voluntary contraction (MVC) and at 80% MVC with duration of 20 s were performed at the beginning of each experiment. Tetanic electrical stimulation was then applied to the main muscle motor point for 20 s with surface electrodes at five stimulation frequencies (20, 25, 30, 35, and 40 Hz). All subjects showed myoelectric manifestations of muscle fatigue consisting of negative trends of spectral variables and conduction velocity and positive trends of amplitude variables. The main findings of this work are 1) myoelectric signal variables obtained from electrically elicited contractions show fluctuations smaller than those observed in voluntary contractions, 2) spectral variables are more sensitive to fatigue than conduction velocity and the average rectified value is more sensitive to fatigue than the root-mean-square value, 3) conduction velocity is not the only physiological factor affecting spectral variables, and 4) contractions elicited at supramaximal stimulation and frequencies greater than 30 Hz demonstrate myoelectric manifestations of muscle fatigue greater than those observed at 80% MVC sustained for the same time.     

Oscillatory interactions between sensorimotor cortex and the periphery

Field potential recordings from motor cortex show oscillations in the beta-band (approximately 20 Hz), which are coherent with similar oscillations in the activity of contralateral contracting muscles. Recent findings have revised concepts of how this activity might be generated in the cortex, suggesting it could achieve useful computation. Other evidence shows that these oscillations engage not just motor structures, but also return from muscle to the central nervous system via feedback afferent pathways. Somatosensory cortex has strong beta-band oscillations, which are synchronised with those in motor cortex, allowing oscillatory sensory reafference to be interpreted in the context of the oscillatory motor command which produced it.     

Oscillatory structure of the parameters of the pulse signal of the radial artery

The typology analysis of the spectral density curves of time series obtained from various parameters of unit pulse oscillations was performed. The formal classification (typology) of spectral curves was performed using correlations of peak values of the spectral density of VLF, LF, and HF slow waves. To include a spectral density curve into a particular type, the criteria were introduced that characterize the intensity of these oscillatory components. The experimental data was collected during examinations of children and adolescents that were performed to detect the early stage of arterial hypertension (AH). The distribution of the subjects among the types of spectral density based on various parameters of pulse oscillation was evaluated. The results of the comparative analysis of spectral type distribution for various parameters are shown. This analysis has revealed the most informative spectral parameters for differential diagnosis of conditions of two types: type 1, essential hypertension, and type 2, various functional disorders with a normal blood pressure. It has been found that the parameters of the oscillatory components of dicrotic pulse wave time characteristics are the most informative for detecting hypertension in children.     

Functional maturation of the brain and formation of the neurophysiological mechanisms of selective voluntary attention in young schoolchildren

A particular role was demonstrated for functional maturation of the frontothalamic system (FTS) of the brain in forming the cerebral organization of selective voluntary attention in ontogeny. Analysis of the coherence of the rhythmic components of the EEG α range in adults and seven-to eight-and nine-to ten-year-old children showed that, if the functional state of the control structures corresponds to the age, the formation of the neurophysiological mechanisms selectively modulating cortical activity and supporting selective tuning of the cerebral structures to the cognitive task is completed by the age of seven or eight years. Unlike adults, children demonstrated no interhemispheric features of the intercenter integration of cortical zones in the prestimulus period of voluntary attention. Children with a functionally immature FTS lacked selective specific integration of cortical zones in the pretuning period. The deficit of selective modulation of cortical activity in children with a functionally immature FTS is considered as the neurophysiological factor that delays the formation of voluntary attention and voluntary control of activity and, finally, leads to learning difficulties.     

Quantitative estimation of connection of the heart rate rhythm with motor activity in rat fetuses

In rat fetuses over E17-20 with preserved placental circulation with use of mathematical analysis there were revealed value and character of connections of slow wave oscillations of the heart rhythm with motor activity for 30 min of observation. In the software PowerGraph 3.3.8, normalization and filtration of the studied signals were performed in three frequency diapasons: D1-0.02–0.2 Hz (5–50 s), D2-0.0083-0.02 Hz (50 s-2 min), and D3-0.0017–0.0083 Hz (2–10 min). The EMG curves filtrated by diapasons or piezograms were compared with periodograms in the corresponding diapasons of the heart rhythm variations. In the software “Origin 8.0”, quantitative estimation of the degree of intersystemic interrelations for each frequency diapason was performed by Pearson correlation of coefficient, by the correlation connection value, and by the time shift of maximum of cross-correlation function. It has been established that in the frequency D1, regardless of age, the connection of heart rhythm oscillations with motor activity is expressed weakly. In the frequency diapason D2, the connection in most cases is located in the zone of weak and moderate correlations. In the multiminute diapason (D3), the connection is more pronounced. The number of animals that have a significant value of the correlation connection rises. The fetal motor activity fires in the decasecond diapason in all age groups are accompanied by short-time decelerations of the heart rhythms. In the minute diapason, there is observed a transition from positive connections in E17 and E18 to the negative ones in E19-20. Results of the study are considered in association with age-related changes of ratios of positive and negative oscillations of the heart rhythm change depending on the character of motor activity.     

Fatigue Effect on Low-Frequency Force Fluctuations and Muscular Oscillations during Rhythmic Isometric Contraction

Continuous force output containing numerous intermittent force pulses is not completely smooth. By characterizing force fluctuation properties and force pulse metrics, this study investigated adaptive changes in trajectory control, both force-generating capacity and force fluctuations, as fatigue progresses. Sixteen healthy subjects (20–24 years old) completed rhythmic isometric gripping with the non-dominant hand to volitional failure. Before and immediately following the fatigue intervention, we measured the gripping force to couple a 0.5 Hz sinusoidal target in the range of 50–100% maximal voluntary contraction. Dynamic force output was off-line decomposed into 1) an ideal force trajectory spectrally identical to the target rate; and 2) a force pulse trace pertaining to force fluctuations and error-correction attempts. The amplitude of ideal force trajectory regarding to force-generating capacity was more suppressed than that of the force pulse trace with increasing fatigue, which also shifted the force pulse trace to lower frequency bands. Multi-scale entropy analysis revealed that the complexity of the force pulse trace at high time scales increased with fatigue, contrary to the decrease in complexity of the force pulse trace at low time scales. Statistical properties of individual force pulses in the spatial and temporal domains varied with muscular fatigue, concurrent with marked suppression of gamma muscular oscillations (40–60 Hz) in the post-fatigue test. In conclusion, this study first reveals that muscular fatigue impairs the amplitude modulation of force pattern generation more than it affects the amplitude responsiveness of fine-tuning a force trajectory. Besides, motor fatigue results disadvantageously in enhancement of motor noises, simplification of short-term force-tuning strategy, and slow responsiveness to force errors, pertaining to dimensional changes in force fluctuations, scaling properties of force pulse, and muscular oscillation.     

Firing properties of motor units during fatigue in subjects after stroke.

The purpose of this work was to investigate the electromyographic (EMG) fatigue representations in muscles of subjects after stroke at the level of motor unit, based on the analysis of mean power frequency (MPF) in the power density spectrum (PDS) for intramuscular EMG and our previous modeling and experiment studies on the neuromuscular transmission failure (NTF). NTF due to the local muscular fatigue had been captured in motor unit signals from healthy subjects during a submaximal fatigue contraction previously. In this study, the EMG signals for the biceps brachii muscles were collected by needle electrodes from the affected and unaffected arms of six hemiplegic subjects after stroke, and from the dominated arm of six healthy subjects during a full maximum voluntary contraction (MVC) and a subsequent 20% MVC. The MPF of EMG trials detected intramuscularly during the full and 20% MVCs, and the parameters of motor unit action potential trains (MUAPTs) during 20% MVC were analyzed in three groups: the normal (from healthy subjects), unaffected (from subjects after stroke), and affected (from subjects after stroke). It was found that during the full MVC the MPFs of the normal and unaffected groups decreased more than the affected when monitored by a moving time window of 2 s. The comparison on the overall MPF during the full MVC for these three groups over the whole time course of the EMG signal (18 s) were: the affected overall MPF was higher than the unaffected (P < 0.05); and the unaffected overall MPF was larger than the normal (P < 0.05). However, no significant decrease in MPF was found for these three groups during 20% MVC. The NTF was captured in most MUAPTs in the groups of the normal and unaffected rather than in the affected group, symbolized by the lowered rates of change (RCs) of firing rate (FR) (P < 0.05), more MUAPTs with positive RCs of maximum oscillation (MO) in MUAPT power density spectra (P < 0.05), and the significant higher RCs of minimum inter-pulse interval (MINI) (P < 0.05) in the normal and unaffected compared to the affected group. Enhanced neural drives to the motor units of the unaffected and affected groups were observed during 20% MVC, which possibly came from the bilateral neural inputs due to the disinhibition of the ipsilateral projections in subjects after stroke. For identifying the fatigue associated with NTF, the motor unit firing parameters, FR, MINI, and MO, were more sensitive than the MPF. The results obtained in this work provided a further understanding on the EMG of the fatigue processes in paretic and non-paretic muscles during voluntary contractions.     

Neuromuscular fatigue of elbow flexor muscles of dominant and non-dominant arms in healthy humans.

The purpose of this study was to assess differences in fatigue-related changes in variables related to structures within the neuromuscular system, between the dominant and non-dominant elbow flexor muscles of right-handed individuals. Two experimental sessions were performed on the right arm and one on the left arm. For each session, maximum voluntary torque, level of voluntary activation, M-wave amplitude, twitch/train or twitch/doublet torque ratio and EMG median frequency were obtained before and up to 20 min after a sustained maximum isometric fatigue task. Our main results were: 1) reproducible fatigue-induced changes in all variables of interest between the two sessions performed with the right arm, 2) significantly greater failure in voluntary activation and neuromuscular propagation with sustained activity for the non-dominant compared with dominant side, and 3) no effect of dominance on MVC torque, endurance time, and fatigue-induced changes in EMG median frequency and elicited torques. These results suggest that the preferential use of elbow flexor muscles with the dominant arm leads to more fatigue resistance in certain structures/mechanisms of the neuromuscular system, but not in others.     

Peculiarities of formation of the cognitive functions in junior school children with different maturity of regulatory brain systems

To reveal the specific role of maturation of modulating, regulatory brain systems in formation of cognitive processes at the junior school age, was performed a complex electroencephalographic and neuropsychological examination of the 7–8-year-old children with different degrees of functional maturity of the regulatory systems. It has been shown that an essential factor determining formation of the higher psychic functions (HPF) at the junior school age is maturation of the fronto-thalamic system. Immaturity of this system in the 7–8-year-old children leads to a deficiency of functions of programming, regulation, and control of the activity. The most substantial changes were revealed for the components of the voluntary organization of the activity, which are connected with its selectivity both in realization of current tasks and in creation of the activity strategy. The deficiency of processes of voluntary regulation in the 7–8-year-old children with immaturity of the fronto-thalamic system is combined with a delay of development of the meaning-forming speech function. Comparison of data of the neuropsychological and electroencephalographic examination has permitted suggesting that the basis of the revealed changes in the HPF formation in the 7–8-year-old children is immaturity of the main neurophysiological mechanisms that provide a selective involvement of different cortical regions in providing their activity both in the course of its realization and during preparation to it as well as an under-development of differentiated intracortical connections in the left hemisphere.Translated from Zhurnal Evolyutsionnoi Biokhimii i Fiziologii, Vol. 40, No. 5, 2004, pp. 427–435.Original Russian Text Copyright © 2004 by Machinskaya, Semenova.To the 100-Anniversary of N. N. Traugott     

Neurobiology of muscle fatigue.

Muscle fatigue encompasses a class of acute effects that impair motor performance. The mechanisms that can produce fatigue involve all elements of the motor system, from a failure of the formulation of the descending drive provided by suprasegmental centers to a reduction in the activity of the contractile proteins. We propose four themes that provide a basis for the systematic evaluation of the neural and neuromuscular fatigue mechanisms: 1) task dependency to identify the conditions that activate the various mechanisms; 2) force-fatigability relationship to explore the interaction between the mechanisms that results in a hyperbolic relationship between force and endurance time; 3) muscle wisdom to examine the association among a concurrent decline in force, relaxation rate, and motor neuron discharge that results in an optimization of force; and 4) sense of effort to determine the role of effort in the impairment of performance. On the basis of this perspective with an emphasis on neural mechanisms, we suggest a number of experiments to advance our understanding of the neurobiology of muscle fatigue.     

Aldehyde dehydrogenase activity in rat cerebral structures

By means of the quantitative histochemical method aldehyde dehydrogenase (AldDG; acidic phosphatase 1.2.1.3.) activity has been studied in neuronal structures of all parts of the rat CNS. The greatest activity has been revealed in cytoplasm of receptor (nucleus of the mesencephalic tract trigeminal nerve-1,100 stipulated units) and effector (all motor nuclei of the trunk and spinal cord: 500-800 stipulated units) cerebral neurons. In perikaryons and axons of most of the intercalated neurons AldDG activity is not great (200-300 stipulated units). A positive correlation is found between distribution of AldDG activity among the forebrain structures, on the one hand, and density of dopaminergic terminals, dopamine content and MAO activity of these structures--on the other. In the metencephalon similar correlation is found between AldDG activity and noradrenaline content and density of serotoninergic terminals. A direct dependence is stated of AldDG activity on phylogenic age of the cerebral structures. The data presented demonstrate that AldDG activity is connected with those cerebral structures that are supposed to possess, in the process of common and mediatory metabolism, a high level of natural synthesis of aldehydes.     

Specific features of regulatory and information-related components of cognitive processes in 7-10-year-old children with local EEG abnormalities in the right hemisphere

Two groups of 7-10-year-old children were formed on the basis of the results of visual analysis of their EEG. The first group included 15 children with local EEG deviations in the right hemisphere, and the second group included 21 children without EEG deviations from the age norm (control group). In both groups, verbal and nonverbal higher mental functions and the ability to voluntary control of activity were assessed by means of neuropsychological methods. As compared to children of the control group, children with local EEG deviations in the right hemisphere demonstrated some difficulties in strategy formation, reduced ability to maintain already formed programs, increased fatigue, changes in affective behavior (anxiety and behavioral excitability), deficit of visual and somatosensory perceptual synthesis, reduction in object recognition efficiency, and visual memory deficit.