Sladjan Milanovic

Impairment of cortical inhibition in writer's cramp as revealed by changes in electromyographic silent period after transcranial magnetic stimulation.

Changes in silent period (SP) duration following transcranial magnetic stimulation (TMS) set at 20% above the motor threshold were studied in six subjects suffering from writers cramp, while performing dystonic movement and during voluntary isometric contraction of the muscles mostly involved in the dystonic movement. Dependency of SP duration on the intensity of preceding muscle contraction was compared on both affected and healthy side. In all subjects SP duration during dystonic contraction was shorter than during voluntary contraction of the similar strength performed with the same hand. Also, in five subjects, SP duration during dystonic contraction was shorter than during voluntary contraction of the similar strength performed with the healthy hand. In addition, the SP duration on the affected side was negatively associated with the intensity of the preceding contraction (i.e. the stronger contraction the shorter SP), while on the healthy side it was not the case. It is concluded that central inhibitory mechanisms are abnormal in writers cramp.

Central changes in muscle fatigue during sustained submaximal isometric voluntary contraction as revealed by transcranial magnetic stimulation

Changes in responses to transcranial magnetic stimulation (TMS) during submaximal isometric voluntary contraction (60% of maximal voluntary contraction (MVC) of the adductor pollicis muscle and the subsequent recovery period have been studied in healthy volunteers. TMS at twice the motor threshold was applied during the sustained contraction, as well as at rest and during short-lasting (2 s) 60% MVCs before and immediately after the sustained contraction, and at 5 min intervals during the recovery period. Both motor evoked potential (MEP) magnitude (peak and area) and silent period (SP) duration in electromyographic activity (EMG) of the adductor pollicis muscle showed a gradual decrease up to the endurance point and an increase thereafter. MEPs elicited at rest immediately after the fatiguing contraction were larger, whereas those elicited later on during the recovery period did not differ significantly from the controls. It is suggested that the changes in responses to TMS, divergent from those in ongoing voluntary EMG during the sustained 60% MVC, indicate complex processes at levels preceding the motor cortex output cells in an attempt to maintain a submaximal contraction of the fatigued muscle. The increase in MEP magnitude after the sustained 60% MVC may indicate residual changes in cortical activity after fatiguing contraction.

Changes in movement final position associated with agonist and antagonist muscle fatigue.

Abstract We have tested the hypothesis that agonist and antagonist muscle fatigue could affect the final position of rapid, discrete movements. Six subjects performed consecutive elbow flexion and extension movements between two targets, with their eyes closed prior to, and after fatiguing the elbow extensor muscles. The results demonstrate that elbow extension movements performed in the post-test period systematically undershot the final position as compared to pre-test movements. However, attainment of the aimed final position in elbow flexion movements was unaffected by fatiguing of the extensor muscles. Undershoot of the final position obtained in extension movements was associated with agonist muscle fatigue, a result that was expected from the point of view of current motor control theories, and that could be explained by a reduced ability of the shortening muscle to exert force. On the other hand, the absence of the expected overshoot of the final position when the antagonist is fatigued, indicates the involvement of various reflex and/or central mechanisms operating around the stretched muscle that could contribute to returning the limb to the standard final position after a brief prominent overshoot.

A comparison of the effects of agonist and antagonist muscle fatigue on performance of rapid movements

Abstract The aim of this study was to investigate the effects of agonist and antagonist muscle fatigue on the performance of rapid, self-terminating movements. Six subjects performed rapid, consecutive elbow flexion and extension movements between two targets prior to and after fatiguing either the elbow flexor or elbow extensor muscles. The experiments demonstrated consistent results. Agonist muscle fatigue was associated with a decrease in peak velocity and peak deceleration, while a decrease in peak acceleration was particularly prominent. Antagonist muscle fatigue, however, was associated with a decrease in peak deceleration, while a decrease in both the peak velocity and peak acceleration was modest and, in some tests, non-significant. The relative acceleration time (i.e. acceleration time as a proportion of the total movement time) increased when agonists were fatigued, but decreased when antagonists were fatigued. Taken together, these results emphasize the mechanical roles of the agonist and antagonist muscles; namely, the fatigue of each muscle group particularly affected the movement phase in which that group accelerated a limb, while changes of the movement kinematics pattern provided more time for action of the fatigued muscles. In addition, the results presented suggest that agonist muscle fatigue affects movement velocity more than antagonist muscle fatigue, even in movements that demonstrate prominently both mechanical and myoelectric activity of the antagonist muscles, such as rapid, self-terminating movements.

Transcranial application of near-infrared low-level laser can modulate cortical excitability

Near‐infrared low‐level laser (NIR‐LLL) irradiation penetrates scalp and skull and can reach superficial layers of the cerebral cortex. It was shown to improve the outcome of acute stroke in both animal and human studies. In this study we evaluated whether transcranial laser stimulation (TLS) with NIR‐LLL can modulate the excitability of the motor cortex (M1) as measured by transcranial magnetic stimulation (TMS).

History of exposure to dopaminergic medication does not affect motor cortex plasticity and excitability in Parkinson’s disease

OBJECTIVE Little is known whether and how chronic exposure to dopaminergic treatment alters physiological mechanisms in Parkinsons disease (PD). METHODS Two clinically similar groups of PD patients, one consisting of drug-naïve patients and another of patients already on chronic dopaminergic medication (when off medication), were compared to each other and to a control group. Plasticity and excitability of the hand primary motor cortex of the more affected side were evaluated using transcranial magnetic stimulation (TMS) techniques. RESULTS There was little difference between two patient groups, and both groups showed similar differences in comparison to controls: decreased facilitatory sensory-motor plasticity (as measured by paired associative stimulation [PAS] protocol), impaired short-interval intracortical inhibition (SICI), and diminished slope of input-output curves at higher TMS intensities. The exception was that 30 min after PAS, intracortical facilitation (ICF) was significantly reduced in drug-naïve patients, whereas it changed much less in other two groups. CONCLUSIONS Chronic exposure to dopaminergic drugs does not affect substantially the features of motor cortex excitability and plasticity in PD. There is little interaction between plasticity and excitability features of motor cortex in PD. SIGNIFICANCE Reduced response to facilitatory PAS protocol, reduced SICI, and reduced slope of the input-output curve at higher TMS pulse intensities, seem to be physiological markers for the presence of the pathological disease process in PD. Long term treatment does not seem to change the underlying physiology of the disease.

Changes in Cortical Inhibition During Task-Specific Contractions in Primary Writing Tremor Patients

Primary writing tremor (PWT) is a rare disease of unknown pathophysiology. We studied changes in silent period (SP) duration, after transcranial magnetic stimulation (TMS), set at 20% above the motor threshold in 6 PWT patients and 7 healthy control subjects. SP duration was tested during a task‐specific act, i.e., writing that induced tremor in all patients in the affected hand (Wr); nonspecific voluntary contraction of intensity, matching that developed during writing (VCWr); and during near maximal voluntary contraction (VCNmax). There were no differences in SP duration during Wr and VCWr contraction on the right affected side or between sides in both PWT patients and control subjects, nor between the groups. However, during VCNmax, SP significantly shortened on both sides in PWT patients, whereas there were no changes in control subjects. Although it appears that inhibitory mechanism are not directly involved in the generation of the tremulous activity, the shortening of SP indicates that central inhibitory mechanisms are affected in PWT patients. Therefore, whereas the underlying pathophysiological mechanisms in PWT and writers cramp may share common features, the results indicate that PWT is not a variant of focal task‐specific dystonia but rather a separate nosological entity.

Changes in movement kinematics during single-joint movements against expectedly and unexpectedly changed inertial loads

Abstract The study had two goals: (1) to understand the role of peripheral and central factors in changes in the movement symmetry ratio (acceleration time divided by deceleration time); and (2) to compare several theories of motor control with respect to their ability to predict changes in a number of kinematic indices when movements are performed against expectedly and unexpectedly changed inertial loads. Subjects performed elbow flexion movements from a standard initial position to a fixed target “as fast as possible” against three different inertial loads. In some trials, prior to the movement, the load was changed unexpectedly for the subject. Then the load remained the same for a block of trials, then changed again, and so on. We assumed that the first trial of a block was performed using central control patterns associated with moving a different expected load used in the previous block of trials. The main findings included: (a) the equifinality of movements in all conditions, irrespective of actual and expected loads; (b) a decrease in peak velocity and an increase in movement time when the actual load increased; (c) no significant changes in peak velocity and movement time when moving against a load while expecting a different load; and (d) symmetry ratio decreased with actual load and increased with expected load. Separate analyses of the effects of changes of expected and actual loads showed different slopes of the relation between peak velocity and movement symmetry ratio. Based on the last findings we conclude that movement symmetry is defined by both peripheral factors, possibly related to the role of damping forces, and by central control patterns. The equilibrium-point (EP) hypothesis is able to handle the findings better than torque-control models which make wrong predictions with respect to findings (a), (c), and (d) or a model combining control of torque patterns with specification of a final equilibrium position which makes wrong predictions with respect to findings (c).

Improvement of language functions in a chronic non-fluent post-stroke aphasic patient following bilateral sequential theta burst magnetic stimulation

In chronic non-fluent aphasia patients, inhibition of the intact right hemisphere (RH), by transcranial magnetic stimulation (TMS) or similar methods, can induce improvement in language functions. The supposed mechanism behind this improvement is a release of preserved left hemisphere (LH) language networks from RH transcallosal inhibition. Direct stimulation of the damaged LH can sometimes bring similar results too. Therefore, we developed a novel treatment approach that combined direct LH (Broca’s area (BA)) stimulation, by intermittent theta burst stimulation (TBS), with homologue RH area’s inhibition, by continuous TBS. We present the results of application of 15 daily sessions of the described treatment approach in a right-handed patient with chronic post-stroke non-fluent aphasia. The intervention appeared to improve several language functions, but most notably propositional speech, semantic fluency, short-term verbal memory, and verbal learning. Bilateral TBS modulation of activation of the language-related areas of both hemispheres seems to be a feasible and promising way to induce recovery in chronic aphasic patients. Due to potentially cumulative physiological effects of bilateral stimulation, the improvements may be even greater than following unilateral interventions.

Paired-associative stimulation can modulate muscle fatigue induced motor cortex excitability changes.

The aim of this study was to examine whether the changes of the motor cortex excitability induced by muscle fatigue could be affected by prior or subsequent intervention protocol supposed to induce opposing excitability changes. For this purpose we used paired associative stimulation (PAS) method, where peripheral nerve stimuli were associated with transcranial magnetic stimulation (TMS) of the motor cortex at a fixed interstimulus interval of 25 ms. The PAS protocol used is known to produce a long lasting, long-term potentiation (LTP) like change of cortical plasticity manifested by significant increase in motor evoked potentials (MEPs) amplitude. In this study, we confirmed significant MEP size reduction following fatigue, which had been already reported in the literature. When PAS was applied either immediately before or after muscle fatigue protocol, the excitability changes were largely occluded and MEP sizes remained close to baseline levels. However, in spite of the effects on cortical excitability, conditioning with PAS did not cause any change in target fatigue measure, the endurance point, which remained the same as when fatiguing protocol was applied alone. The present results demonstrate that fatigue-related changes in cortical excitability can be modulated by either prior or subsequent excitability promoting activity. They also suggest that muscle fatigue associated changes in motor cortical excitability probably represent non-specific activity-related plasticity, rather than a direct expression of the so-called central fatigue.