Carlo Trompetto

Clinical and research methods for evaluating cortical excitability.

Summary The evaluation of motor cortical output after transcranial magnetic stimulation (TMS) is a means of investigating how the motor cortex reacts to external stimuli (i.e., a method to assess the excitability of the motor cortex). The recording of the descending volleys at the surface of the spinal cord provides a direct measure of the motor cortical output. However, this approach is highly invasive and can be used only during particular conditions. On the other hand, electromyographic recordings of the motor phenomena induced by TMS provide a completely painless, noninvasive, indirect measure of the cortical output, with these phenomena obviously reflecting the excitability of the spinal motoneurons as well as that of the muscle itself. The authors review how the electromyographic activity induced by TMS can provide valuable information about motor cortical excitability for use in clinical practice and research.

The excitability of the human motor cortex increases during execution and mental imagination of sequential but not repetitive finger movements

Motor potentials (MEPs) evoked by focal (figure-of-eight coil) transcranial magnetic stimulation of the left motor cortex were recorded from the right opponens pollicis (OP) and flexor digitorum superficialis (FDS) of 14 normal subjects during different motor tasks. Changes in motor cortical excitability under behavioural conditions presumably connected with premotor and supplementary motor area (SMA) activation were investigated by comparing the size of the MEPs obtained during: (1) rest, (2) mental calculus, (3) repetitive left thumb-to-index opposition, (4) mental simulation of the same task with the right hand, (5) sequences of left thumb-to-fingers opposition, and (6) mental simulation of the same sequences with the right hand. MEP size significantly increased in both muscles during sequential movements of the left hand and sequence simulation with the right hand, but not during mental calculus or actual or simulated repetitive movements. The H-reflex evoked in the OP and FDS muscles by electrical stimulation of the median nerve (at wrist and elbow, respectively) under the same experimental conditions did not show significant modifications. The increase in MEP size during non-routine actual or imagined sequences of finger movements supports the view that the SMA is activated under these conditions and that it exerts a direct facilitatory influence on the motor cortex.

Motor recovery following stroke: a transcranial magnetic stimulation study

OBJECTIVES To verify the usefulness of early recording of motor evoked potentials (MEPs) in predicting motor outcome after stroke and to investigate the neural mechanisms underlying functional recovery following stroke. METHODS We performed a comparative analysis of the behaviour of motor responses evoked by transcranial magnetic stimulation (TMS) of the ipsilateral and contralateral motor cortex in the affected and unaffected thenar muscles of 21 consecutive patients with acute stroke. RESULTS According to the behaviour of MEPs in the affected muscles, patients could be divided into 3 groups: (a) 10 subjects with absent responses to TMS of both the damaged and undamaged hemisphere, whose motor recovery was poor and related to the size of MEPs on the normal side; (b) 5 subjects with larger MEPs upon TMS of the ipsilateral (undamaged) than of the contralateral (damaged) cortex, whose good recovery possibly resulted from the emergence of ipsilateral pathways; (c) 6 subjects with larger MEPs in the affected than in the unaffected muscles, whose good recovery was possibly subserved by alternative circuits taking over cortical deafferentation. CONCLUSIONS Early MEP recording in acute stroke provides useful information on the clinical prognosis and the different mechanisms of motor recovery.

Central effects of botulinum toxin type A: Evidence and supposition

No convincing evidence exists that botulinum toxin type A (BT‐A) injected intramuscularly at therapeutic doses in humans acts directly on central nervous system (CNS) structures. Nevertheless, several studies, using various approaches, strongly suggest that BT‐A affects the functional organization of the CNS indirectly through peripheral mechanisms. By acting at alpha as well as gamma motor endings, BT‐A could alter spindle afferent inflow directed to spinal motoneurons or to the various cortical areas, thereby altering spinal as well as cortical mechanisms. Muscle afferent input is tightly coupled to motor cortical output, so that the afferents from a stretched muscle go to cortical areas where they can excite neurons capable of contracting the same muscle. The BT‐A–induced reduction in spindle signals could, therefore, alter the balance between afferent input and motor output, thereby changing cortical excitability.

Changes of intracortical inhibition during motor imagery in human subjects.

Paired-pulse transcranial magnetic stimulation with a conditioning-test paradigm was used to assess changes of corticocortical inhibition and facilitation during mental simulation of sequential finger movements in normal subjects. The cortico-cortical inhibition (at interstimulus interval, ISI, of 3 ms) was significantly reduced in the relaxed opponens pollicis (OP) muscle during motor imagery, regardless of the absolute size of the test motor evoked potential. The amount of cortico-cortical inhibition was similar to that observed during a mild voluntary contraction of the OP. No change of cortico-cortical facilitation was observed at the ISI of 12 ms. The data support the hypothesis that similar neural structures, including the primary motor cortex, are activated during both mental simulation and actual execution of motor activities.

Selective facilitation of responses to cortical stimulation of proximal and distal arm muscles by precision tasks in man.

1. The responses of the first dorsal interosseus (1DI), opponens pollicis (OP), extensor digitorum communis (EDC), brachioradialis (BR), biceps brachii (BB) and anterior deltoid (AD) muscles to magnetic stimulation of the motor cortex were recorded during different motor tasks. 2. Two precision and two power isometric tasks were investigated. The precision tasks were a pincer grip (‘grip’) and a thrust against a target with the wrist (‘push’). In the former, the prime movers were the intrinsic hand muscles, while the proximal muscles played a postural role. In the latter, the prime movers were the proximal muscles. In both tasks, force was controlled through visual feedback. The power tasks required encirclement of a cylinder with the fingers (‘grasp’), or sustaining a weight suspended at wrist level (‘load’). 3. Magnetic stimulation was applied in eight subjects by a coil placed over the vertex at 1.1‐1.2 times the motor threshold for the most excitable muscles. This produced in the prime mover muscles larger motor‐evoked responses (MEPs) during grip or push tasks than grasp or load tasks, in spite of similar background EMG levels. During grip tasks, only one of the two prime movers showed task‐dependent changes. In the postural muscle AD there was no significant difference between MEPs during grip and grasp tasks; however, BB responses were larger during grasp than grip tasks. 4. MEPs simultaneously recorded in the prime movers were plotted against each other. The slope of the regression line for AD versus BB was larger in push than load tasks, whilst the changes in MEPs of 1DI and OP were independent during both grip and grasp tasks. 5. In three subjects, MEPs were also elicited by electrical stimulation during grip and grasp tasks. MEP changes tended to parallel those obtained for magnetic stimulation, but the increase in size of the electrically evoked MEPs during the precision task was smaller. 6. In all subjects the median and ulnar nerves were stimulated during grip and grasp tasks, and an H reflex was evoked in the hand muscles of five subjects. In no case did the two tasks produce reflexes of different amplitude. 7. The motor response of both proximal and distal muscles can be task dependent, in spite of the differences in their principal functional role and cortical representation. The modulation is related to the degree of control requested by the task, and is likely to reflect selective changes in the excitability of corticospinal neurones.

Comparison of intracortical inhibition and facilitation in distal and proximal arm muscles in humans

1 Cortico‐cortical inhibition and facilitation induced by paired transcranial magnetic stimulation (TMS) of the human motor cortex were investigated in the distal muscle opponens pollicis (OP) and the proximal muscle biceps brachii (BB) of normal subjects. 2 The test response evoked by TMS (125 % of motor threshold, MTh) in the relaxed OP and BB muscles was inhibited by a conditioning TMS (80 % of MTh) at short interstimulus intervals (ISIs; 2‐5 ms) and facilitated at longer ISIs (10‐25 ms). The test response was significantly less inhibited at short ISIs and more facilitated at long ISIs in the BB than OP. 3 The MTh at rest was significantly lower for the OP than for the BB, indicating a greater excitability of OP cortical area. However, the above pattern of inhibition and facilitation was preserved both when the stimulus intensity was adjusted to evoke test responses of matched size in the two muscles and within an ample range of conditioning stimulus intensities. 4 The use of a circular coil or a focal figure‐of‐eight coil produced no qualitative differences in the pattern of inhibition and facilitation in either muscle. 5 The significant difference in MTh between muscles was lost during voluntary activation. In both muscles, pre‐innervation abolished the cortico‐cortical facilitation and reduced the cortico‐cortical inhibition. However, the latter remained larger in the OP than BB muscle. 6 We suggest that the different potency of intracortical inhibitory and facilitatory circuits directed towards distal and proximal arm muscles is related to their diverse prevalent functions.

Intracortical inhibition and facilitation are abnormal in Huntington's disease: a paired magnetic stimulation study.

Transcranial magnetic stimulation with a conditioning-test paradigm was used to assess cortico-cortical interactions in the motor cortex of 11 patients with Huntingtons disease (HD) as compared to normal controls (NC). In the HD patients, threshold and amplitude of motor potentials evoked in the opponens pollicis muscle at rest were not significantly different from NC. The cortico-cortical inhibition at interstimulus intervals of 2-5 ms was significantly reduced and the cortico-cortical facilitation at longer intervals (10-25 ms) was significantly enhanced. Changes of intracortical inhibition and facilitation were related to clinical rating of choreic dyskinesias. The data support the hypothesis of a functional impairment of the motor cortex-basal ganglia loop in HD patients.

Botulinum toxin changes intrafusal feedback in dystonia: A study with the tonic vibration reflex

To investigate the possible role of botulinum toxin (BT‐A) injection in reducing muscle afferent feedback, we evaluated electrophysiologically 10 right‐handed patients with writers cramp before and 3 weeks after treatment. The ratio between pre‐ and postinjection values of maximal M‐wave (M‐max), maximal voluntary contraction (MVC), and tonic vibration reflex (TVR) were measured in the injected muscles (wrist flexors or extensors). In all the subjects, BT‐A injection reduced the TVR more than the M‐max and MVC (mean ratio ± SD: TVR, 0.24 ± 0.22; MVC, 0.59 ± 0.32; M‐max, 0.68 ± 0.24; P = 0.003). Long‐term evaluation of 2 patients disclosed that, after 7 months, when some clinical benefits persisted, M‐max and MVC had fully recovered, whereas the TVR was still depressed. This special sensitivity of the TVR to suppression by BT‐A injection could be mediated by the chemodenervation of intrafusal muscle fibers, leading to a reduction in spindle inflow to the central nervous system during vibration. The action on intrafusal fibers could alter sensorimotor integration, thus contributing to the clinical benefits of BT‐A injection.

Consensus paper on short-interval intracortical inhibition and other transcranial magnetic stimulation intracortical paradigms in movement disorders

In this article we reviewed the results obtained with the technique of paired-pulse transcranial magnetic stimulation (TMS) in normal subjects and in patients with movement disorders (Parkinsons disease, dystonia, chorea, Tourettes syndrome, myoclonus, essential tremor, and ataxia). Results on short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and long-interval intracortical inhibition (LICI) are reported and discussed for each type of movement disorder.