Significance of local synchronization and oscillatory processes of thalamic neurons in goal-directed human behavior

The time-frequency characteristics and interaction in the cell ensembles of the nonspecific (CM-Pf) and motor (Voi) thalamus were analyzed. Neuronal activity was registered by microelectrode technique during 18 stereotactic neurosurgery operations in spasmodic torticollis patients. The presentation of functionally significant verbal stimuli was accompanied by the emergence of short-term (0.5–1.5 s) local synchronization and stabilization of the oscillatory (3–6 Hz) activity in neighboring neurons of the nonspecific (CM-Pf) thalamus. These focuses of synchronized oscillatory neuronal activity were correlated with the moment of the greatest concentration of selective attention. A similar phenomenon of shortterm synchronization was observed in the motor (Voi) and nonspecific (CM-Pf) thalamus of the human brain during voluntary movements. Synchronization of neuronal activity occurred at the height of the implementation of the motor act, correlating with the maximum muscle tension, as well as in the aftereffect of the voluntary movement. In general, the findings suggest an important role of the local oscillations (3–6 Hz) and synchronization of thalamic neurons in the mechanisms of the relevant information transmission during goal-directed human behavior.     

Botulinum A toxin for the treatment of adult-onset spasmodic torticollis

Thirty-five patients with adult-onset idiopathic torticollis were treated by local injections of botulinum A toxin into dystonic cervical muscles. Substantial improvement with respect to reduction and elimination of pain was found in 81 percent, improvement in posture deformity and involuntary spasms in 70 percent, increased range of motion of the neck in 78 percent, reduction in visible sternocleidomastoid hypertrophy in 86 percent, and improvement in tremor in 65 percent. The syndrome was divided into four subtypes based on pattern of dystonic muscle groups involved in the dystonia, head and shoulder posture, and sternocleidomastoid muscle hypertrophy. Injection strategy based on this subdivision is described.     

The investigation of control mechanisms of stepping rhythm in human in the air-stepping conditions during passive and voluntary leg movements

In unloading condition the degree of activation of the central stepping program was investigated during passive leg movements in healthy subjects, as well as the excitability of spinal motoneurons during passive and voluntary stepping movement. Passive stepping movements with characteristics maximally approximated to those during voluntary stepping were accomplished by experimenter. The comparison of the muscle activity bursts during voluntary and imposed movements was made. In addition to that the influence of artificially created loading onto the foot to the leg movement characteristics was analyzed. Spinal motoneuron excitability was estimated by means of evaluation of amplitude modulation of the soleus H-reflex. The changes of H-reflexes under the fixation of knee or hip joints were also studied. In majority of subjects the passive movements were accompanied by bursts of EMG activity of hip muscles (and sometimes of knee muscles), which timing during step cycle was coincided with burst timing of voluntary step cycle. In many cases the bursts of EMG activity during passive movements exceeded activity in homonymous muscles during voluntary stepping. The foot loading imitation exerted essential influence on distal parts of moving extremity during voluntary as well passive movements, that was expressed in the appearance of movements in the ankle joint and accompanied by emergence and increasing of phasic EMG activity of shank muscles. The excitability of motoneurons during passive movements was greater then during voluntary ones. The changes and modulation of H-reflex throughout the step cycle without restriction of joint mobility and during exclusion of hip joint mobility were similar. The knee joint fixation exerted the greater influence. It is supposed that imposed movements activate the same mechanisms of rhythm generation as a supraspinal commands during voluntary movements. In the conditions of passive movements the presynaptic inhibition depend on afferent influences from moving leg in the most degree then on central commands. It seems that afferent inputs from pressure receptors of foot in the condition of "air-stepping" actively interact with central program of stepping and, irrespective of type of the performing movements (voluntary or passive), form the final pattern activity.     

Readiness potentials recorded from the scalp and depth leads.

Readiness potentials on voluntary hand movements were recorded from the scalp (C3, C4), premotor cortex, subcortical white matter and VL nucleus of the thalamus. Subjects were healthy right-handed men and patients with involuntary movement disorders. We obtained a slow negative shift of brain electrical potentials from the scalp and cortex preceding voluntary hand movements. The mean time interval between the onset of the readiness potential and the onset of motor activity (mean T) was 0.8 sec on right hand movements and 1.0 sec on left hand movements in healthy men. In cases with parkinsonism, the mean T value was 1.4 sec in patients with akinesia, 1.1 sec in those without akinesia. The amplitude of readiness potentials was higher in the scalp contralateral to the hand movement. The readiness potentials recorded from the VL nucleus and white matter were reversed in polarity from those of scalp and cortex. Simultaneous recordings from cortex and VL nucleus showed early onset of readiness potentials from the cortex by approximately 0.1 sec compared with the VL nucleus.     

Influence of Vibration on Motor Responses in the Upper Arm Muscles under Stationary Conditions and during Voluntary and Evoked Arm Movements under Limb Unloading Conditions

Locomotion of mammals, including humans, is based on the rhythmic activity of spinal cord circuitries. The functioning of these circuitries depends on multimodal afferent information and on supraspinal influences from the motor cortex. Using the method of transcranial magnetic stimulation (TMS) of arm muscle areas in the motor cortex, we studied the motor evoked potentials (MEP) in the upper arm muscles in stationary conditions and during voluntary and vibration-evoked arm movements. The study included 13 healthy subjects under arm and leg unloading conditions. In the first series of experiments, with motionless limbs, the effect of vibration of left upper arm muscles on motor responses in these muscles was evaluated. In the second series of experiments, MEP were compared in the same muscles during voluntary and rhythmic movements generated by left arm m. triceps brachii vibration (the right arm was stationary). Motionless left arm vibration led to an increase in MEP values in both vibrated muscle and in most of the non-vibrated muscles. For most target muscles, MEP was greater with voluntary arm movements than with vibration-evoked movements. At the same time, a similar MEP modulation in the cycle of arm movements was observed in the same upper arm muscles during both types of arm movements. TMS of the motor cortex significantly potentiated arm movements generated by vibration, but its effect on voluntary movements was weaker. These results indicate significant differences in the degree of motor cortex involvement in voluntary and evoked arm movements. We suppose that evoked arm movements are largely due to spinal rather than central mechanisms of generation of rhythmic movements.     

The investigation of locomotor activity control system in humans under the air-stepping conditions during passive and voluntary leg movements

The degree of activation of the central stepping program during passive leg movement was studied in healthy subjects under unloading conditions; the excitability of spinal motoneurons was studied during passive and voluntary stepping movements. Passive stepping movements with characteristics maximally close to those during voluntary stepping were accomplished by the experimenter. The bursts of muscular activity during voluntary and imposed stepping movements were compared. In addition, the influence on the leg movement of artificially created loading onto the foot was studied. The excitability of spinal motoneurons was estimated by the amplitude of modulation of the m. soleus H reflex. Changes in the H reflex (Hoffmann’s reflex) after fixation of the knee and hip joints were also studied. In most subjects, passive movements were accompanied by bursts of electromyographic (EMG) activity in the hip muscles (sometimes in shank muscles); the timing of the EMG burst during the step cycle coincided with the burst’s timing during voluntary stepping. In many cases, the bursts in EMG activity exceeded the activity of homonymous muscles during voluntary stepping. Simulation of foot loading influenced significantly the distal part of the moving extremity during both voluntary and passive movements, which was expressed in the appearance of movements in the ankle joint and an increase in the phasic EMG activity of the shank muscles. The excitability of motoneurons during passive movements was higher than during voluntary movements. Changes and modulation of the H reflex throughout the step cycle were similar without restriction of joint mobility and without hip joint mobility. Fixation of the knee joint was of great importance. It is supposed that imposed movements activate the same mechanisms of rhythm generation as supraspinal commands during voluntary movements. During passive movements, presynaptic inhibition depends mostly on the afferent influences from the moving leg rather than on the central commands. Under the conditions of “air-stepping,” the afferent influences from the foot pressure receptors are likely to interact actively with the central program of stepping and to determine the final activity pattern irrespective of the movement type (voluntary or passive).     

Observations and analysis of results in 131 cases of spasmodic torticollis after selective denervation

In 131 patients treated exclusively by selective denervation during the past 10 years, all or almost all the abnormal movements of spasmodic torticollis were suppressed in 115 (88%) while preserving posture and mobility. This approach was also used in certain forms of adult-onset dystonia. An appreciable amount of abnormal movements remained in the other patients, either due to residual innervation or because of limitation of denervation necessary to preserve normal movements (laterocollis) or neck stability (retrocollis). A medio-lateral approach to the posterior cervical region in the sitting position using stimulation under light anaesthesia is recommended.     

Mutual influences of upper and lower extrimities during cyclic movements

The possibility of muscle activation of passive arm during its cyclic movements, imposed by active movements of contralateral arm or by experimenter was studied, as well as the influence of lower extremities cyclic movements onto arm muscles activity. In addition to that the activity of legs muscles was estimated in dependence on motor task condition for arms. Ten healthy supine subjects carried out opposite movements of arms with and without stepping-like movements of both legs. The experiment included three conditions for arm movements: 1) the active movements of both arms; 2) the active movements of one arm, when other entirely passive arm participated in the movement by force; 3) passive arm movement caused by experimenter. In the condition 2) additional load on active arm was applied (30 N and 60 N). In all three conditions the experiment was carried out with arms movements only or together with legs movements. The capability of passive moving arm muscles activation depended on increasing afferent inflow from muscles of contralateral arm was demonstrated. Emerging electrical activity was modulated in the arms movements cycle and depended on the degree of active arm loading. During combined active movements of arms and legs the reduction of activity in the flexor muscles of shoulder and forearm was observed. Concomitant arms movements increased the magnitude ofelectromiographic bursts during passive stepping-like movements in the most of recorded muscles, and the same increasing was only observed in biceps femoris and tibialis anterior muscles during active legs movement. The increasing of loading of one arm caused essential augmentation of EMG-activity in the majority of recording legs muscles. The data obtained are the additional proof of existence of functionally significant neuronal interaction both between arms and between upper and lower extremities, which is evidently depend on the intraspinal neuronal connections.     

Are interlimb interactions disturbed in patients with Parkinson’s disease? A study under unloading conditions

During natural human locomotion, neural connections are activated that are typical of regulation of the quadrupedal walking. The interaction between the neural networks generating rhythmic movements of the upper and lower limbs depends on tonic state of each of these networks regulated by motor signals from the brain. Distortion of these signals in patients with Parkinson’s disease (PD) may lead to disruption of the interlimb interactions. We examined the effect of movements of the limbs of one girdle on the parameters of the motor activity of another limb girdle at their joint cyclic movements under the conditions of arm and leg unloading in 17 patients with PD and 16 healthy subjects. We have shown that, in patients, the effect of voluntary and passive movements of arms, as well as the active movement of the distal parts of arms, on the voluntary movement of legs is weak, while in healthy subjects, the effect of arm movements on the parameters of voluntary stepping is significant. The effect of arm movements on the activation of the involuntary stepping by vibrational stimulation of-legs in patients was absent, while in healthy subjects, the motor activity of arms increased the possibility of involuntary rhythmic movements activation. Differences in the effect of leg movements on the rhythmic movements of arms were found in both patients and healthy subjects. The interlimb interaction appeared after drug administration. However, the effect of the drug was not sufficient for the recovery of normal state of the neural networks in patients. In PD patients, neural networks generating stepping rhythm have an increased tonic activity, which prevents the activation and appearance of involuntary rhythmic movements facilitating the effects of arms on legs.     

Abnormalities of mutual influences of the upper and lower limbs after a stroke

The common pattern of muscle activation and specifics of interlimb neuronal connections during the performance of rhythmic separate and simultaneous arm and leg movements in the lying position in healthy subjects, which reflected functionally significant interlimb neuronal interactions, were shown. The study was designed to investigate these mutual influences of the upper and lower limbs during the performance of similar motor tasks by stroke patients. Sixteen poststroke patients with different degrees of hemiparesis performed active and passive arm movements simultaneously with stepping leg movements or without them while lying supine. It was demonstrated that the patients had a disordered common pattern of distribution of muscle activity when they performed voluntary cyclic movements with both arms. Passive movements of both paretic and nonparetic arms led to different degrees of activation of their muscles, depending on the degree of paresis: in patients with mild paresis, muscle activation was similar to that in healthy subjects; in patients with severe paresis, it was insignificant. The loading of the nonparetic arm resulted in an increase in the activity in the paretic arm shoulder flexor muscles in patients with mild paresis (which was typical of healthy subjects), while loading did not influence significantly patients with severe paresis. The combination of cyclic arm movements and stepping leg movements in diagonal synergy decreased the activity in the proximal muscles of both arms, irrespective of the degree of paresis, as it was observed in healthy subjects. Simultaneous arm and leg movements did not change the muscle activity in nonparetic legs in either groups of patients, but the activity in the paretic leg muscles even decreased. The results obtained revealed important features of poststroke motor disturbances, which caused changes in interlimb interactions and largely depended on the degree of paresis. The data could be useful for developing new methods for the performance of rehabilitative procedures in poststroke patients.     

Activation of interlimb interactions increases the motor output in legs of healthy subjects: Study under the conditions of arm and leg unloading

The effect of arm movements and movements of individual arm joints on the electrophysiological and kinematic characteristics of voluntary and vibration-triggered stepping-like leg movements was studied under the conditions of horizontal support of the upper and lower limbs. The horizontal support of arms provided a significant increase in the rate of activation of locomotor automatism by noninvasive impact on tonic sensory inputs. The addition of active arm movements during involuntary stepping-like leg movements led to an increase in the EMG activity of hip muscles and was accompanied by an increase in the amplitude of hip and shin movements. The movement of the shoulder joints led to an increase in the activity of hip muscles and was accompanied by an increase in the amplitude of hip and shin movements. Passive arm movements had the same effect on induced leg movements. The movement of the shoulder joints led to an increase in the activity of hip muscles and an increase in the amplitude of movements of knee and hip joints. At the same time, the movement of forearms and wrists had a similar facilitating effect on the physiological and kinematic characteristics of rhythmic stepping-like movements, but influenced the distal segments of legs to a greater extent. Under the conditions of subthreshold vibration of leg muscles, voluntary arm movements led to activation of involuntary rhythmic stepping movements. During voluntary leg movements, the addition of arm movements had a significantly smaller impact on the parameters of rhythmic stepping than during involuntary leg movements. Thus, the simultaneous movements of the upper and lower limbs are an effective method of activation of neural networks connecting the rhythm generators of arms and legs. Under the conditions of arm and leg unloading, the interactions between the cervical and lumbosacral segments of the spinal cord seem to play the major role in the impact of arm movements on the patterns of leg movements. The described methods of activation of interlimb interactions can be used in the rehabilitation of post-stroke patients and patients with spinal cord injuries, Parkinson’s disease, and other neurological diseases.     

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.     

Role of the human thalamic parafascicular (CM-Pf) complex in neuronal mechanisms of selective attention

Responses of 93 single units of the human thalamic CM-Pf complex to relevant and irrelevant verbal (or sensory) stimuli were studied using microelectrode technique in alert diskinetic patients suffering from the tonic forms of spasmodic torticollis during 11 stereotaxic operations. The response patterns of two types units with irregular unitary (A-type) and low-threshold bursting Ca(2+)-dependent (B-type) spike activity were studied. Three main conclusions emerge from the studies: 1) high reactivity of both A- and B-units to presentation of relevant verbal stimuli with differences of their response patterns as determined by the type of constituent elements; 2) close functional connectivity of these neuronal changes with the level of selective attention; 3) at the moment of attention activation, the appearance of transient interneuronal interactions between adjacent A and B cells characterized by the local synchronization and stabilization of rhythmic oscillations. These data point to considerable contribution of the thalamic CM-Pf complex and its neuronal mechanisms into organization of the human selective attention and triggering verbal-related processing during performance of purposive speech-provoked voluntary acts.     

Some circuit operations in the mammalian brain

There is an account of the basis neuronal connectivities of the spinal cord with the Sherringtonian principles of divergence and convergence. Neurones act synaptically either as excitatory or as inhibitory, depending on the specific transmitter substances liberated. Inhibitory neurones usually act either in a feedback or a feedforward manner. Voluntary movement is considered in relation to the instructions delivered to the motor cortex in order to produce the discharges down the pyramidal tract that evoke the required movement. There is an account of the three lines of evidence which indicate that in voluntary movements the primary neural event arises in discharges of neurones of the supplementary motor area (SMA). There are three main circuits from the SMA that activate subroutines concerned in the preprogramming of movements: (1) SMA to the basal ganglia, thence to the thalamus with a collateral line through the substantia nigra, thence to the association cortex; (2) SMA to cerebellar hemisphere via the pontine nuclei, thence to the nucleus dentatus, to the thalamus, to the association cortex, and (3) SMA to association cortex both frontal and parietal. According to the SMA hypothesis the liaison brain for intention is located in the SMA, there being reciprocity of informational flow from the mental events of intention to the neuronal events in the SMA.     

Electromyographic investigations in torticollis.

In 13 patients with torticollis, the electromyographic (EMG) activity in the neck muscles at rest was investigated before, during and after stimulation of the H1 bundle (in horizontal torticollis) and inner part of oral ventral nucleus (in the rotatory form), as well as after coagulation. Three EMG types of torticollis-spasmodic, myoclonic and mixed - could be differentiated. During the 8-, 25- and 50-Hz stimulations, a diminution in the amplitude and frequency of muscle potentials, followed by electric silence, was most often obtained; in general, the electric silence was preceded by a rhythmic activity of grouped potentials. Following coagulation, no spontaneous EMG activity was any longer recorded in the neck muscles, in the majority of the cases.     

Somatosensory evoked potentials in the ventrolateral thalamus

Within the target area (VL) used for the stereotactic treatment of parkinsonian tremor and spasmodic torticollis, electrical stimulation as well as recording of somatosensory evoked potential (SEP) was performed. The effects of stimulation in the target area are facilitation of muscle tone showing some degree of somatotopic distribution. The recorded SEPs indicate a projection of an afferent system (probably of muscle afferents) to the target area. We assume that the target area is a relay station involved in the control of muscle tone. The interruption of muscle afferents in combination with the correct somatotopic localization of the lesion is important for the therapeutic efficacy in parkinsonian tremor and spasmodic torticollis.     

Mutual influences of upper and lower extremities during cyclic movements

The possibility for the activation of muscles in a passive arm during its cyclic movements imposed by active movements of the contralateral arm or by an experimenter and the effect that the movements of lower extremities have on the activity of the arm muscles have been studied. In addition, the activity of the leg muscles was studied as dependent on the motor task performed by the arms. Ten healthy subjects performed antiphase arm movements with and without stepping-like movements of both legs in the supine position. The experiment was performed under three conditions for the arm movements: (1) both arms performed active movements; (2) one arm performed active movements, and the contralateral arm, being entirely passive, was forced to participate in movements; (3) the movement of the passive arm was caused by an experimenter. Under condition (2), additional loadings of 30 and 60 N were applied to the active arm. Under all conditions, the arm movements were performed with and without leg movements. The possibility for the activation of muscles in the arm performing passive movements has been demonstrated. To a large extent, this is possible due to an increase in the afferent inflow from the muscles of the contralateral arm. The electrical activity was modulated during cyclic arm movements and depended on the level of loading of the active arm. During the combined active movements of the arms and legs, the reduction in the activity of the flexor muscles of the shoulder and forearm was observed. In the case of passive stepping-like movements, the concomitant arm movements increased the magnitude of electromyographic bursts in most of the examined leg muscles. During active leg movements, a similar increase in electromyographic bursts was observed only in the m. biceps femoris (BF) and the anterior tibial muscle. An increase in the loading of one arm caused a significant increase in the EMG activity in most examined muscles of the legs. The data obtained provide additional proof for the existence of a functionally significant neuronal interaction between the arms, as well as between the upper and lower extremities, which is probably due to intraspinal neuronal connections.     

Treatment of severe neuroleptic-induced tardive torticollis

BACKGROUND: The aim of this paper is to describe a case of severe neuroleptic-induced tardive torticollis successfully treated with a combination of clozapine, clonazepam and botulinum toxin-A. CASE REPORT: The patient, a 30-year old man with a seven-year history of delusional disorder experienced severe right torticollis with painful tightness of the neck and elevation of the shoulder. At this time he was receiving haloperidol 20 mg, trifluoperazine 5 mg, zuclopenthixol 20 mg and biperidine 4 mg daily. The combination therapy with clozapine and clonazepam and the long-term use of botulinum toxin-A resulted in a complete remission of dystonic movements. CONCLUSIONS: The present observations provide evidence indicating that this combination therapy may be of benefit in patients with severe neuroleptic-induced tardive torticollis.     

Oscillatory coupling in writing and writer's cramp.

Writing is a highly skilled and overlearned movement. In patients suffering from writer's cramp, a focal task-induced dystonia, writing is impaired or even impossible due to involuntary muscle contractions and abnormal posture, which occur as soon as the person picks up a pen or within writing a few words. The underlying pathophysiological mechanisms of this movement disorder are not fully understood up to now. The aim of the present study was to unravel the oscillatory network underlying physiological writing in healthy subjects and dystonic writing in writer's cramp patients. Using whole-head magnetoencephalography (MEG) and the analysis tool dynamic imaging of coherent sources (DICS) we studied oscillatory neural coupling during writing in eleven healthy subjects and eight patients suffering from writer's cramp. Simultaneous recording of brain activity with MEG and activity of forearm and hand muscles with surface electromyography (EMG) was performed while subjects were writing for five minutes with their dominant right hand. Applying DICS sources of strongest cerebro-muscular coherence and cerebro-cerebral coherence during writing were identified, which consistently included six brain areas in both, the control subjects and the patients: contralateral and ipsilateral sensorimotor cortex, ipsilateral cerebellum, contralateral thalamus, contralateral premotor and posterior parietal cortex. Coherence between cortical sources and muscles appeared primarily in the frequency of writing movements (3-7 Hz) while coherence between cerebral sources occurred primarily around 10 Hz (8-13 Hz). Interestingly, consistent coupling between both sensorimotor cortices was observed in patients only, whereas coupling between ipsilateral cerebellum and the contralateral posterior parietal cortex was found in control subjects only. These results are consistent with the often described bilateral pathophysiology and impaired sensorimotor integration in writer's cramp patients.     

Role of computerized transverse axial tomography on stereotactic surgery of the diencephalon. A preliminary report of 67 cases.

67 cases of various functional disorders of the diencephalon were examined by EMI scanner. The patients were composed of 38 cases of parkinsonism, 7 cases of thalamic syndrome, 6 cases of choreoathetoid movement, 2 cases of dystonia, 11 cases of involuntary movement of unknown etiology and 1 case of torticollis, tic, and ballismus, respectively. In parkinsonism, 79% showed diffuse cerebral atrophy, 5% had focal low density in the substantia nigra and the thalamus, whereas 16% remained normal. Pre- and postoperative assessment with CT scan was briefly discussed with reference to stereotactic surgery of the diencephalon.