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Cerebellar-related long latency motor response in upper limb musculature by transcranial magnetic stimulation of the cerebellum
Abstract
In this study, we aimed to identify the cerebellum-related electromyographic (EMG) response that appeared in the upper limbs musculature. Thirty times averaged transcranial magnetic stimulation (TMS) with a double-cone coil placed over the cerebellar hemisphere elicited long latency EMG responses at the bilateral extensor carpi radialis (ECR) muscles. The peak latency of this EMG response was 70.7±12.7 ms in the ipsilateral ECR and 62.9±10.2 ms in the contralateral ECR of the TMS side. These latencies were much longer than the latency of the muscle evoked potential when we stimulated pyramidal tracts at the foramen magnum level. Cerebellar hemisphere loading by the finger target pursuit test made this EMG response faster during TMS on the ipsilateral side of the cerebellum and slower during TMS on the contralateral side of the cerebellum. Furthermore, the deeper the level of drowsiness, the slower the peak latency of this EMG response became. These results suggest that this EMG potential is a specific response of the cerebellum and brainstem reticular formation, and may be conducted from the cerebellar structure to the ECR muscle through the polysynaptic transmission of the reticulospinal tract.
... However, some studies have reported a motor response in the proximal limb in animals by invasive direct electrical stimulation [5][6][7]. Some recent studies reported a long-latency motor response on an EMG by cerebellar TMS using a noninvasive method [31][32][33][34][35][36]. Interestingly, these motor responses appeared under specific conditions, which modulated their latency or probability of appearance (Table 1). ...
... Therefore, this long-latency motor response on an EMG induced by cerebellar TMS of the soleus muscle may be mediated by extrapyramidal tracts such as the vestibulospinal tract. Subsequently, Hosokawa et al. reported that this long-latency motor response induced by cerebellar TMS was found in the extensor carpi radialis (ECR) muscle, and that its latency was modulated by the degree of postural control and drowsiness [36]. Their findings indicate that this long-latency motor response may be mediated by the brainstem's reticular formation because the reticulospinal tract is activated during postural control [37], and the reticulothalamic pathway is deactivated depending on the degree of drowsiness [38]. ...
... Their findings indicate that this long-latency motor response may be mediated by the brainstem's reticular formation because the reticulospinal tract is activated during postural control [37], and the reticulothalamic pathway is deactivated depending on the degree of drowsiness [38]. Based on a series of reports by Yorifuji and colleagues [32,33,36], extrapyramidal tracts, especially the vestibulospinal and reticulospinal tracts, are thought to be involved in the long-latency motor response to cerebellar TMS. However, this response can be confirmed only with a very specific low-frequency (2-20 Hz) bandpass filter. ...
Since individuals with cerebellar lesions often exhibit hypotonia, the cerebellum may contribute to the regulation of muscle tone and spinal motoneuron pool excitability. Neurophysiological methods using transcranial magnetic stimulation (TMS) of the cerebellum have been recently proposed for testing the role of the cerebellum in spinal excitability. Under specific conditions, single-pulse TMS administered to the cerebellar hemisphere or vermis elicits a long-latency motor response in the upper or lower limb muscles and facilitates the H-reflex of the soleus muscle, indicating increased excitability of the spinal motoneuron pool. This literature review examined the methods and mechanisms by which cerebellar TMS modulates spinal excitability.
... C-TMS induced not only a short-latency inhibitory effect on the contralateral primary motor area but also longlatency electromyographic (EMG) bursts on the bilateral soleus muscles in standing humans [6]. The latency of the EMG bursts was modulated by optokinetic stimulation, activating the vestibulospinal tract [7] and resulting in drowsiness, through a change in reticulospinal tract activity [8]. These findings indicate that C-TMS also promotes the excitability of the spinal motoneuron pool through components of the extrapyramidal tract, such as the vestibulospinal or reticulospinal tract. ...
... Therefore, the long-latency EMG response induced by C-TMS may be useful for the identification of disorder sites other than the projections that can be identified with CBI. However, this long-latency EMG response cannot be induced in resting-state muscle [6][7][8]. ...
... In the first experiment, we investigated the time course of C-TMS effects on the soleus H-reflex in the participants' resting-state soleus muscle. If cerebellar spinal facilitation (CSpF) can be induced by C-TMS, it may present the possibility of using CSpF to identify disorder sites that cannot be identified with CBI in patients who cannot stand or voluntarily contract the test muscles, because the long-latency EMG response induced by C-TMS is not observed in resting-state muscles [6,8,12]. ...
We investigated whether cerebellar transcranial magnetic stimulation (C-TMS) facilitates the excitability of the ipsilateral soleus motoneuron pool in resting humans, and whether the facilitation is modulated by a task that promotes cerebellar activity. A test tibial nerve stimulus evoking the H-reflex from the right soleus muscle was delivered before or after conditioning C-TMS in prone individuals. The amplitude of the H-reflex was significantly increased at conditioning-test interstimulus intervals of 110, 120, and 130 ms. Furthermore, we revealed that this facilitation effect was inhibited while the individuals tapped their right index finger. These findings indicate that C-TMS facilitates spinal motoneuronal excitability with an ∼100 ms latency in resting humans, and that this cerebellar spinal facilitation is modulated by a task that might increase cerebellar activity. Cerebellar spinal facilitation could thus be useful for assessing the excitability of the cerebellum, or the cerebellar output to spinal motoneurons.
... This cerebellar spinal facilitation (CSpF) [107,108] is modulated by motor tasks [107], which require cerebellar excitation [109]. In contrast, cerebellar TMS induces long latency electromyographic response (C-LER) in the hand muscles [110][111][112] particularly during visually guided manual tracking tasks and in the lower muscles [113][114][115], which can be mediated by the vestibulospinal and reticulospinal tracts because C-LER is affected by the task-modulated excitability of these tracts [114,115]. Therefore, CSpF and C-LER may be useful to detect the function of cerebellar output and that of the cerebellum itself. ...
... This cerebellar spinal facilitation (CSpF) [107,108] is modulated by motor tasks [107], which require cerebellar excitation [109]. In contrast, cerebellar TMS induces long latency electromyographic response (C-LER) in the hand muscles [110][111][112] particularly during visually guided manual tracking tasks and in the lower muscles [113][114][115], which can be mediated by the vestibulospinal and reticulospinal tracts because C-LER is affected by the task-modulated excitability of these tracts [114,115]. Therefore, CSpF and C-LER may be useful to detect the function of cerebellar output and that of the cerebellum itself. ...
Ataxia, the incoordination and balance dysfunction in movements without muscle weakness, causes gait and postural disturbance in patients with stroke, multiple sclerosis, and degeneration in the cerebellum. The aim of this article was to provide a narrative review of the previous reports on physical therapy for mainly cerebellar ataxia offering various opinions. Some systematic reviews and randomized control trial studies, which were searched in the electronic databases using terms “ataxia” and “physical therapy,” enable a strategy for physical therapy for cerebellar ataxia. Intensive physical therapy more than 1 hour per day for at least 4 weeks, focused on balance, gait, and strength training in hospital and home for patients with degenerative cerebellar ataxia can improve ataxia, gait ability, and activity of daily living. Furthermore, the weighting on the torso, using treadmill, noninvasive brain stimulation over the cerebellum for neuromodulation to facilitate motor learning, and neurophysiological assessment have a potential to improve the effect of physical therapy on cerebellar ataxia. Previous findings indicated that physical therapy is time restricted; therefore, its long-term effect and the effect of new optional neurophysiological methods should be studied.
... These responses could be associated with eye-hand coordination or with the detection of and correction for visuomotor errors [63]. Hosokawa et al. (2014) [66] Fig. 7 Averaged TMS-evoked potentials before and after cTBS at 80% of the AMT (left) and before and after iTBS at 90% of the AMT (right). Grand average pre-and post-stimulation waveforms are shown as recorded at the C3 electrode (a). ...
... These responses could be associated with eye-hand coordination or with the detection of and correction for visuomotor errors [63]. Hosokawa et al. (2014) [66] Fig. 7 Averaged TMS-evoked potentials before and after cTBS at 80% of the AMT (left) and before and after iTBS at 90% of the AMT (right). Grand average pre-and post-stimulation waveforms are shown as recorded at the C3 electrode (a). ...
Transcranial magnetic and electric stimulation of the brain are novel and highly promising techniques currently employed in both research and clinical practice. Improving or rehabilitating brain functions by modulating excitability with these noninvasive tools is an exciting new area in neuroscience. Since the cerebellum is closely connected with the cerebral regions subserving motor, associative, and affective functions, the cerebello-thalamo-cortical pathways are an interesting target for these new techniques. Targeting the cerebellum represents a novel way to modulate the excitability of remote cortical regions and their functions. This review brings together the studies that have applied cerebellar stimulation, magnetic and electric, and presents an overview of the current knowledge and unsolved issues. Some recommendations for future research are implemented as well.
... In a previous study, C-TMS induced motor responses on soleus EMG with a latency of about 100 ms in standing humans [22]. The latency was affected by optokinetic stimulation activating the vestibulospinal tract [23] and by a change in drowsiness, which modulated the activity of the reticulospinal tract [24]. These findings indicate that the C-TMS effect on soleus EMG in the standing human may be mediated by the vestibulospinal tract or the reticulospinal tract. ...
Previously, we reported that cerebellar transcranial magnetic stimulation (C-TMS) facilitates spinal motoneuronal excitability in resting humans. In this study, we aimed to characterize the descending pathway that is responsible for the C-TMS-associated cerebellar spinal facilitation. We evaluated the effect of C-TMS on ipsilateral soleus Ia presynaptic inhibition (PSI) and reciprocal inhibition (RI) because the vestibulospinal and reticulospinal tracts project from the cerebellum to mediate spinal motoneurons via interneurons associated with PSI. PSI and RI were measured with a soleus H-reflex test following operant conditioning using electrical stimulation of the common peroneal nerve. C-TMS was delivered before test tibial nerve stimulation with conditioning-test interstimulus intervals of 110 ms. C-TMS did not generate motor-evoked potentials, and it did not increase electromyography activity in the ipsilateral soleus muscle, indicating that C-TMS does not directly activate the corticospinal tract and motoneurons. However, C-TMS facilitated the ipsilateral soleus H-reflex and reduced the amount of soleus Ia PSI, but not RI. These findings indicate that C-TMS may facilitate the excitability of the spinal motoneuron pool via the vestibulospinal or reticulospinal tracts associated with PSI. Cerebellar spinal facilitation may be useful for assessing the functional connectivity of the cerebellum and vestibular nuclei or reticular formation.
The cerebellum is crucially important for motor control and adaptation. Recent non-invasive brain stimulation studies have indicated the possibility to alter the excitability of the cerebellum and its projections to the contralateral motor cortex, with behavioral consequences on motor control and adaptation. Here we sought to induce bidirectional spike-timing dependent plasticity (STDP)-like modifications of motor cortex (M1) excitability by application of paired associative stimulation (PAS) in healthy subjects. Conditioning stimulation over the right lateral cerebellum (CB) preceded focal transcranial magnetic stimulation (TMS) of the left M1 hand area at an interstimulus interval of 2 ms (CB→M1 PAS2 ms), 6 ms (CB→M1 PAS6 ms) or 10 ms (CB→M1 PAS10 ms) or randomly alternating intervals of 2 and 10 ms (CB→M1 PASControl). Effects of PAS on M1 excitability were assessed by the motor-evoked potential (MEP) amplitude, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cerebellar-motor cortex inhibition (CBI) in the first dorsal interosseous muscle of the right hand. CB→M1 PAS2 ms resulted in MEP potentiation, CB→M1 PAS6 ms and CB→M1 PAS10 ms in MEP depression, and CB→M1 PASControl in no change. The MEP changes lasted for 30–60 min after PAS. SICI and CBI decreased non-specifically after all PAS protocols, while ICF remained unaltered. The physiological mechanisms underlying these MEP changes are carefully discussed. Findings support the notion of bidirectional STDP-like plasticity in M1 mediated by associative stimulation of the cerebello-dentato-thalamo-cortical pathway and M1. Future studies may investigate the behavioral significance of this plasticity.
Transcranial magnetic motor cortex stimulation can elicit a series of responses recorded with different latencies from relaxed muscles of the lower limbs. In 7 healthy subjects, ranging in age from 16 to 62 years, stimulation was delivered by a 9 cm coil centered over Cz with the subject in the supine position. Surface polyelectromyography was used to record motor evoked potentials (MEPs) from the quadriceps (QD), hamstrings (HS), tibialis anterior (TA) and triceps surae (TS) muscles bilaterally. Three characteristic responses were identified in each muscle group on the basis of amplitude and latency criteria, identified by latencies: the direct oligosynaptic response MEP30 appeared with a latency of 24.3 msec in the QD, 26.3 msec in the HS, 30.5 msec in the TA and 31.3 msec in the TS; MEP70 with latencies of 64 msec in the QD, 59 msec in the HS, 79 msec in the TA and 72 msec in the TS; MEP120 with latencies of 115 msec in the QD, 126 msec in the HS, 117 msec in the TA and 124 msec in the TS. These 3 responses have distinct latencies, amplitudes and durations. MEP70 appears to be the result of activation of long descending tracts which end on spinal interneuronal circuits. As MEP120 has different features, it may have a different mechanism.
Each of the descending pathways involved in motor control has a number of anatomical, molecular, pharmacological, and neuroinformatic characteristics. They are differentially involved in motor control, a process that results from operations involving the entire motor network rather than from the brain commanding the spinal cord. A given pathway can have many functional roles. This review explores to what extent descending pathways are highly conserved across species and concludes that there are actually rather widespread species differences, for example, in the transmission of information from the corticospinal tract to upper limb motoneurons. The significance of direct, cortico-motoneuronal (CM) connections, which were discovered a little more than 50 years ago, is reassessed. I conclude that although these connections operate in parallel with other less direct linkages to motoneurons, CM influence is significant and may subserve some special functions including adaptive motor behaviors involving the distal extremities.
Key point Increases in the strength of synaptic connections in the motor cortex (long term potentiation) can be induced in humans by repetitively pairing peripheral nerve stimuli and motor cortex transcranial magnetic stimuli given 21–25 ms apart – paired associative stimulation (PAS).
This ‘associative plasticity’ effect has been assumed to relate to synchronicity between sensory input and motor output, with a similar mechanism proposed to underlie effects at all interstimulus intervals.
Here we show that modulation of cerebellar activity using transcranial direct current stimulation can abolish associative plasticity in the motor cortex, but only for sensory/motor stimuli paired at 25 ms, not at 21.5 ms.
The results indicate that human associative plasticity can be affected by cerebellar activity and that at least two different mechanisms are involved in the effects previously reported in studies using PAS at different inter‐stimulus intervals.
The cerebellum plays an important role in movement execution and motor control by modulation of the primary motor cortex (M1) through cerebello-thalamo-cortical connections. Transcranial magnetic stimulation (TMS) allows direct investigations of neural networks by stimulating neural structures in humans noninvasively. The motor evoked potential to single-pulse TMS of M1 is used to measure the motor cortical excitability. A conditioning stimulus over the cerebellum preceding a test stimulus of the contralateral M1 enables us to study the cerebellar regulatory functions on M1. In this brief review, we describe this cerebellar stimulation method and its usefulness as a diagnostic tool in clinical neurophysiology.
The aim of this study was to investigate physiological mechanisms underlying ataxia in patients with ataxic hemiparesis. Subjects were three patients with ataxic hemiparesis, whose responsible lesion was located at the posterior limb of internal capsule (case 1), thalamus (case 2), or pre- and post-central gyri (case 3). Paired-pulse transcranial magnetic stimulation (TMS) technique was used to evaluate connectivity between the cerebellum and contralateral motor cortex. The conditioning cerebellar stimulus was given over the cerebellum and the test stimulus over the primary motor cortex. We studied how the conditioning stimulus modulated motor evoked potentials (MEPs) to the cortical test stimulus. In non-ataxic limbs, the cerebellar stimulus normally suppressed cortical MEPs. In ataxic limbs, the cerebellar inhibition was not elicited in patients with a lesion at the posterior limb of internal capsule (case 1) or thalamus (case 2). In contrast, normal cerebellar inhibition was elicited in the ataxic limb in a patient with a lesion at sensori-motor cortex (case 3). Lesions at the internal capsule and thalamus involved the cerebello-thalamo-cortical pathways and reduced the cerebellar suppression effect. On the other hand, a lesion at the pre- and post-central gyri should affect cortico-pontine pathway but not involve the cerebello-thalamo-cortical pathways. This lack of cerebello-talamo-cortical pathway involvement may explain normal suppression in this patient. The cerebellar TMS method can differentiate cerebellar efferent ataxic hemiparesis from cerebellar afferent ataxic hemiparesis.
Previous studies showed that transcranial magnetic stimulation (TMS) to the cerebellum evokes a long latency motor response in the soleus muscle during a postural task. The cerebellum is activated not only during postural tasks but also during motor tasks for which eye-hand coordination is required. The purpose of this study was to investigate whether TMS over the cerebellum evokes long latency motor responses in the hand during a visually guided manual tracking task. Eight healthy humans tracked an oscillatory moving target with the right index finger or pointed the finger at a stationary target, and TMS was delivered to the scalp over the cerebellum during the motor tasks. Trials with sham TMS were inserted between the trials with cerebellar TMS. The trajectory of finger movement fluctuated 92 ms after cerebellar TMS with a 24% probability during tracking of a moving target. The fluctuation was preceded by an electromyographic burst in the first dorsal interosseous muscle starting at 65 ms after TMS. The probability of fluctuation evoked by cerebellar TMS was significantly larger than that evoked by sham TMS during tracking of a moving target. This significant difference was absent in trials during which subjects pointed their index finger at a stationary target. These findings indicate that cerebellar TMS evokes a long latency motor response during a visually guided manual tracking task. The long latency motor response may be related to cerebellar activity associated with eye-hand coordination or to the detection of and correction for visuomotor errors.
The cerebellar dentate and interpositus nuclei and the area of their efferent fibres have been stimulated in Cebus monkeys, using a movable microcathode. Responses consisted of eye and face movements and a stereotyped flexion of proximal parts of extremities. Very few distal limb movements were seen. The activation of proximal muscles was studied most closely. It consisted of the limited number of 5 movements: arm flexion and shoulder elevation in the forelimb and hip flexion, knee flexion and dorsiflexion of the ankle in the hindlimb. With currents of up to 100 microamperemeter these movements were elicited more readily from the interpositus and the area of efferent fibres of both nuclei as compared to the dentate nucleus. Responses were more often seen in forelimb than in hindlimb muscles, without apparent somatotopy in either nucleus. Combined forelimb-hindlimb movements were elicited from 42 per cent of effective points. Lesions placed at various locations of cerebellar output pathways demonstrated that the responses were mediated by the descending branch of brachium conjunctivum and did not require the activation of structures anterior to and including the red nucleus. The responses are interpreted to represent adjustments in flexor posture that may serve to modify maintained antigravity tonus during the initiation of volitional movements. This function, mediated by brain-stem structures, is considered to be closely associated with the activity of the lateral and intermediate cerebellum during initiation and conduction of volitional movements, which is mediated mainly through the cerebral cortex. It is stressed that control over both flexor posture and discrete distal movements is inherent in the initiation of voluntary movements.
The red nucleus and its spinal projections in the pigeon (Columba livia) have been studied using both normal and experimental material. The cytoarchitecture of the nucleus is described on the basis of Nissl-stained sections and reveals an organization generally similar to that of mammals. The large neurons (40-50μm) tend to be located dorsomedially and ventrolaterally at more caudal nuclear levels, while the small-and medium-sized neurons (15-35μm) predominate at rostral levels. However, neurons of all sizes are present throughout the nucleus.
Following lesions of the nucleus, the course of degenerating axons stained with the Fink-Heimer method has been traced throughout the brainstem and spinal cord. The rubrospinal tract crosses the midline, courses past the ventrocaudal aspect of the contralateral nucleus ruber, and then descends rostroventral and lateral to the nucleus tegmenti pontinus. In its caudal continuation the tract lies ventral to the brachium conjunctivum and the entering radix of the trigeminal nerve. It then assumes a ventrolateral position in the caudal brainstem before shifting to a dorsolateral position in the lateral funiculus of the spinal cord. Within the spinal grey the rubrospinal tract terminates in laminae V, VI and to a lesser extent VII.
The possibility of a topographical organization of the nucleus was investigated with injections of horseradish peroxidase into brachial, thracic and lumbar spinal cord. Regardless of the level of injection, labelled neurons of all sizes were present throughout the contralateral nucleus ruber, indicating the absence of an obvious topography.
In decerebrate, unanesthetized cats, the brain stem was longitudinally cut at the midline from its dorsal to ventral surface with the cerebellum kept intact, eliminating neural interactions between the bilateral vestibular nuclei through the brain stem.
Extracellular spike potentials of vestibular type I neurons identified by horizontal rotation were distinctly inhibited by contralateral vestibular nerve stimulation. This crossed inhibition was abolished by removal of the medial part of the cerebellum, indicating that the inhibition was mediated through the cerebellum. Neither aspiration of the flocculus on the recording side nor intravenous administration of picrotoxin eliminated transcerebellar crossed inhibition, suggesting that it is mediated through the cerebellar nuclei. When the fastigial, interposite and dentate nuclei were stimulated, inhibition of vestibular type I neurons was produced only from the contralateral fastigial nucleus. Cerebellocortical stimulation which inhibited fastigial type I neurons suppressed transcerebellar crossed inhibition. Effective sites for suppression of transcerebellar crossed inhibition were localized to lobules VI and VIIa in the vermal cortex on the side of labyrinthine stimulation.
Intracellular recordings were made from type I neurons in the medial vestibular nucleus. Stimulation of the contralateral vestibular nerve and the contralateral fastigial nucleus produced IPSPs in these neurons with the shortest latency of 3.8 msec and 1.8 msec, respectively. The difference between these two latency values approximates the shortest latency of spike initiation of fastigial type I neurons in response to vestibular nerve stimulation. It is postulated that transcerebellar crossed inhibition is mediated through the fastigial nucleus on the side of labyrinthine stimulation.
This review describes the connections between the cerebral cortex and the cerebellum from both the anatomical and physiological points of view. Emphasis is placed on the dynamic properties and integrative properties of the linkages within the cerebrocerebellar loops in order to begin considering the capabilities of the loops and subloops. The problem of somatotopy within the loops is also considered. The possible roles of the lateral and intermediate zones of the cerebellum in the control of movement are discussed. Premotor association areas and the lateral cerebellum may be responsible for the preprograming of movements. Once the motor command is formulated and transmitted from the motor cortex to the spinal cord, the pars intermedia would update the preprogramed movement, based on the peripheral sensory inputs. Deficiencies in present knowledge are indicated and approaches to these problems are suggested.
Somatosensory evoked potentials (SEPs) evoked by electrical stimulation of the median nerve at the wrist were conditioned by a preceding magnetic stimulus given over the contralateral central scalp using interstimulus intervals of 0-50 msec. The conditioning stimulus had no effect on the size of sub-cortical or N20 components of the response, but caused a large increase in the P25 parietal wave. Later components (P40/N65) of the SEP were reduced in size. The optimum position for producing the effect was with the magnetic stimulator held over the best point on the scalp for evoking muscle responses in the contralateral hand. The threshold for affecting the SEP was approximately the same as the threshold for evoking EMG responses in active hand muscles. We conclude that the magnetic conditioning shock changed the excitability of somatosensory cortex neurones involved in producing the P25. The subsequent decrease in the later components of the SEP may be related to the increase in somatosensory detection thresholds produced by a conditioning magnetic shock.
Magnetic stimulation performed with a double-cone coil placed over appropriate positions on the back of the head reduced the size of electromyographic responses evoked by magnetic cortical stimulation in the first dorsal interosseous muscle when it preceded the cortical stimulus by 5, 6, and 7 msec. No suppression of responses to electrical cortical stimulation occurred. Greater suppression was evoked by stronger cerebellar stimuli; lesser suppression was elicited by stronger cortical stimuli. These physiological findings correspond to those obtained with electrical cerebellar stimulation. The most effective position for magnetic stimulation over the back of the head was slightly rostral to the foramen magnum level on the ipsilateral side of the muscle studied. This indicates that the conditioning stimulus activates certain structures at the back of the head on the ipsilateral side of the muscle, consistent with the cerebellum, because the part of the cerebellum regulating limb muscles is positioned about there on the ipsilateral side. In 2 patients with only cerebellar dysfunction, this suppression effect was not elicited, which also supports that the suppression is caused by activity in cerebellar structures. We conclude that magnetic stimulation over the cerebellum with a double-cone coil elicits the same suppressive effect on the motor cortex as electrical stimulation, but with less discomfort; moreover, we believe that this effect is produced by activation of certain cerebellar structures.
Magnetic stimulation done with a double cone coil placed over the back of the head activated descending motor pathways and produced electromyographic responses in muscles of the arms and legs. The latencies of these responses were the same as those of responses to electrical brainstem stimulation. The threshold was lowest when the coil was placed over the inion or below it on the median line. Placement of the coil on the side ipsilateral to the muscle was more effective than placement on the contralateral side. These results indicate that activation occurs at the foramen magnum level (just below the pyramidal decussation). Collision experiments that used cortical and magnetic brainstem stimulation indicated that the major part of the responses to the latter stimulation were conducted via the large diameter component of the corticospinal tract. Collision experiments done with the peripheral nerve and magnetic brainstem stimulation showed that this stimulation produced a single descending volley in the descending tract. We conclude that magnetic brainstem stimulation produces a single descending volley in the corticospinal tract at the foramen magnum level with less discomfort.
We applied magnetic stimulation of the corticospinal tract at the foramen magnum level to 19 patients with various neurological disorders. Results were consistent with our previous speculation that activation occurs at the foramen magnum level. This method was clinically useful for the following conditions. (1) Detection of subclinical lesion: one patient who had transient ischemic attack that caused no clinical symptoms at examination was shown to have dysfunction of the corticospinal tract. (2) Multiple lesions: our method disclosed at least one lesion above and below the foramen magnum in two patients with multiple sclerosis. (3) Unmasking of dysfunction of the corticospinal tract masked by peripheral neuropathy: magnetic stimulation showed conduction delay in the corticospinal tract in two patients in whom no pyramidal signs were evident because of muscular atrophy due to neuropathy. One patient had multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy, the other had degenerative ataxia and neuropathy. (4) Association of disorders: conduction delay rostral to the foramen magnum, which should not occur in patients with only cervical myelopathy, was shown in a patient with cervical myeloradiculopathy and amyotrophic lateral sclerosis. We conclude that this magnetic stimulation method which is less painful than electrical stimulation has extensive clinical usefulness.
The course and location of vestibulospinal, reticulospinal and descending propriospinal fibres in man are reported. The investigation was carried out on three patients with supraspinal lesions, four with transection of the spinal cord and 33 with anterolateral cordotomies. The lateral vestibulospinal tract at the medullospinal junction and in the first three cervical segments lies on the periphery of the spinal cord lateral to the anterior roots. It moves to the sulcomarginal angle in the remaining cervical segments. In the thoracic cord, it moves laterally, being traversed by the most lateral of the anterior roots. Reticulospinal fibres descend bilaterally in the spinal cord with a preponderance of ipsilateral fibres. Reticulospinal fibres in general do not form well-defined tracts, but are scattered throughout the anterior and lateral columns. They are intermingled with propriospinal fibres and with ascending and descending fibres of other systems. Most reticulospinal fibres move posterolaterally as they descend. It follows that fibres from the brainstem that enter the cord in the anterior column may be in the lateral column anterior to the lateral corticospinal tract at lower levels. Reticulospinal fibres within the lateral column lie anterior to the lateral corticospinal tract. They consist of scattered fibres between the lateral horn and the periphery, most of them in the medial two-thirds of the column. In addition, they are present in a more compact group, forming a triangle on transverse section on the periphery of the lateral column, immediately anterior to the lateral corticospinal tract. On the periphery of the anterior and anterolateral columns reticulospinal fibres descend as small groups or as a continuous band of fibres. The most medial of these reaches the sacral segments and is included in the sulcomarginal fasciculus. A compact group of fibres, shown previously to be central sympathetic fibres ending in the intermediolateral and intermediomedial cell columns, surrounds the lateral horn. They do not extend throughout the thoracic cord in all cases. Anterior to this group is another group of fibres lying on the anterolateral surface of the anterior horn. As these fibres were degenerating following a pontine lesion, they must be reticulospinal fibres. The fibres were not seen in all cases and they did not always reach the lowest thoracic segments. Reticulospinal fibres enter the grey matter in the zona intermedia and along the anterolateral and anterior surfaces of the anterior horns. Caudal to the cervical enlargement, the number of reticulospinal fibres decreases, and their place is taken by propriospinal fibres. But they are not totally replaced by the propriospinal fibres, for reticulospinal fibres continue down into the lowest sacral segments. Of the propriospinal fibres, the majority are short: descending fibres within the juxtagriseal layer are one to two segments long or less.
Transcranial magnetic stimulation (TMS) with a double cone coil placed over the left lateral side of the basal occiput was able to elicit late electromyographic (EMG) responses at the bilateral soleus muscles (SOL) averaged over 30 stimulation events, with a mean latency of approximately 100 ms. These EMG responses were detected using a low frequency bandpass filter with 0.05 Hz magnetic stimulation on ten healthy subjects in standing posture. As magnetic stimulation over the left basal occiput with a double cone coil can stimulate cerebellar structure, this late response seems to be conducted from the cerebellar structure to the SOL via an as yet unknown descending pathway. Here, we report new late EMG responses in relation to cerebellum or cerebellum related structures.
We performed magnetic stimulation at the level of foramen magnum in healthy subjects to evaluate the long latency response in lower limb muscle. Subjects assumed an upright stance and we recorded electromyographic activities in soleus muscle. A late response at the onset latency of approximately 40 ms was elicited. The late response wasn't induced in other lower limb muscles; anterior tibial muscle, quadriceps femoris muscle, and biceps femoris muscle. Additionally, magnetic stimulation to foot motor cortex, basal occiput and cervical nerve roots did not evoke the response with latency of 40 ms. These results reveal the late response in soleus muscle that has not been previously reported. We speculate that it is involved with the long-loop reflex.
The cerebellum regulates execution of skilled movements through neural connections with the primary motor cortex. A main projection from the cerebellum to the primary motor cortex is a disynaptic excitatory pathway relayed at the ventral thalamus. This dentatothalamocortical pathway receives inhibitory inputs from Purkinje cells of the cerebellar cortex. These pathways (cerebellothalamocortical pathways) have been characterized extensively using cellular approaches in animals. Advances in non-invasive transcranial activation of neural structures using electrical and magnetic stimulation have allowed us to investigate these neural connections in humans. This review summarizes various studies of the cerebellothalamocortical pathway in humans using current transcranial electrical and magnetic stimulation techniques. We studied effects on motor cortical excitability elicited by electrical or magnetic stimulation over the cerebellum by recording surface electromyographic (EMG) responses from the first dorsal interosseous (FDI) muscle. Magnetic stimuli were given with a round or figure eight coil (test stimulation) for primary motor cortical activation. For cerebellar stimulation, we gave high-voltage electrical stimuli or magnetic stimuli through a cone-shaped coil ipsilateral to the surface EMG recording (conditioning stimulation). We examined effects of interstimulus intervals (ISIs) with randomized condition-test paradigm, using a test stimulus given preceded by a conditioning stimulus by ISIs of several milliseconds. We demonstrated significant gain of EMG responses at an ISI of 3 ms (facilitatory effect) and reduced responses starting at 5 ms, which lasted 3-7 ms (inhibitory effect). We applied this method to patients with ataxia and showed that the inhibitory effect was only absent in patients with a lesion at cerebellar efferent pathways or dentatothalamocortical pathway. These results imply that this method activates the unilateral cerebellar structures. We confirmed facilitatory and inhibitory natures of cerebellothalamocortical pathways in humans. We can differentiate ataxia attributable to somewhere in the cerebello-thalamo-cortical pathways from that caused by other pathways.
Studies of stroke patients using functional imaging and transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) demonstrated increased recruitment and abnormally decreased short interval cortical inhibition (SICI) of the M1 contralateral to the lesioned hemisphere (contralesional M1) within the first month after infarction of the M1 or its corticospinal projections.
The authors sought to identify mechanisms underlying decreased SICI of the contralesional M1.
In patients within 6 weeks of their first ever infarction of the M1 or its corticospinal projections, SICI in the M1 of the lesioned and nonlesioned hemisphere was studied using paired-pulse TMS. Interhemispheric inhibition (IHI) was measured by applying TMS to the M1 of the lesioned hemisphere and a second pulse to the homotopic M1 of the nonlesioned hemisphere and vice versa with the patient at rest. The results were compared to M1 stimulation of age-matched healthy controls.
SICI was decreased in the M1 of lesioned and nonlesioned hemispheres regardless of cortical or subcortical infarct location. IHI was abnormally decreased from the M1 of the lesioned on nonlesioned hemisphere. In contrast, IHI was normal from the M1 of the nonlesioned on the lesioned hemisphere. Abnormal IHI and SICI were correlated in patients with cortical but not with subcortical lesions.
In subacute stroke patients, abnormally decreased SICI of a contralesional M1 can only partially be explained by loss of IHI from the lesioned on nonlesioned hemisphere. As decreased SICI of the contralesional M1 did not result in excessive IHI from the nonlesioned on lesioned hemisphere with subsequent suppression of ipsilesional M1 excitability and all patients showed excellent recovery of motor function, decreased SICI of the contralesional M1 may represent an adaptive process supporting recovery.
We previously demonstrated that late electromyographic responses with a latency of 100 ms were evoked bilaterally in soleus muscles following transcranial magnetic stimulation over the left cerebellum. Efferent fibers from the left cerebellum modulate vestibulospinal tract influences on the extensor muscles of the left hindlimb. Here, we investigated whether the vestibulospinal tract mediates this late response. We activated the vestibulospinal tract by optokinetic stimulation. Our results show that the latency of the soleus electromyographic response is shortened by optokinetic stimulation, but the latency of the motor response evoked by the corticospinal tract is unchanged. These findings support our hypothesis that vestibulospinal tracts mediate late electromyographic responses, and allow the development of techniques to assess the human vestibulospinal system function.