[Neurophysiological investigations of information processing in the somato-sensory system]. / Neurophysiologische Untersuchungen zur Informationsverarbeitung im somatosensiblen System.

The ability of the human hand to perform complex sensorimotor tasks such as tactile exploration and grasping is based on 1. exact encoding of somatosensory information by cutaneous mechanoreceptors, 2. elaborated processing of afferent signals in somatosensory relay stations and cortex fields, 3. rapid and effective interaction of sensory feedback with motor programs, and 4. different modes of sensory control, which can be switched over.

[Use of botulinum toxin the the treatment of muscle pain]. / Der Einsatz von Botulinumtoxin in der Therapie von Muskelschmerzen.

The analgesic effects of botulinum toxin (BTX) have been discussed controversially due to substantial placebo effects and flaws in the study designs used. Additionally, pathophysiological concepts of pain and the specific analgesic mechanisms of BTX remain largely unclear. Apart from pain reduction through the well-documented effects of BTX at the neuromuscular endplate, additional analgesic mechanisms, including other synaptic and local effects, have been suggested. Currently, BTX can be recommended for pain treatment in dystonia and spasticity. In myofascial pain syndromes, pain relief by BTX injections has been reported, but definite proof according to evidence-based medicinal criteria is still lacking. In fibromyalgia, there seems to be no analgesic effect. The role of BTX in pain therapy is likely to increase in the future.

Disturbed transcallosally mediated motor inhibition in children with attention deficit hyperactivity disorder (ADHD).

OBJECTIVE: The aim of this study was to investigate mechanisms of motor-cortical excitability and inhibition which may contribute to motor hyperactivity in children with attention deficit hyperactivity disorder (ADHD). METHODS: Using transcranial magnetic stimulation (TMS), involvement of the motor cortex and the corpus callosum was analysed in 13 children with ADHD and 13 sex- and age-matched controls. Contralateral silent period (cSP) and transcallosally mediated ipsilateral silent period (iSP) were investigated. RESULTS: Resting motor threshold (RMT), amplitudes of motor evoked potentials (MEP) and cSP were similar in both groups whereas iSP-latencies were significantly longer (p<0.05) and their duration shorter (p<0.01) in the ADHD group. For the ADHD group iSP duration tended to increase and iSP latency to decrease with age (n.s.). Conners-Scores did neither correlate with iSP-latencies and -duration nor with children's age. CONCLUSIONS: The shortened duration of iSP in ADHD children could be explained by an imbalance of inhibitory and excitatory drive on the neuronal network between cortex layer III-the projection site of transcallosal motor-cortical fibers-and layer V, the origin of the pyramidal tract. The longer iSP-latencies might be the result of defective myelination of fast conducting transcallosal fibers in ADHD. iSP may be a useful supplementary diagnostic tool to discriminate between ADHD and normal children.

Representational cortical plasticity associated with brain tumours: evidence from laser-induced interstitial thermotherapy.

OBJECTIVES: To test the hypothesis that cortical plasticity related to destructive tumour growth is functionally relevant. This hypothesis predicts that function is dependent on the intactness of tissue surrounding the tumour. MATERIAL AND METHODS: Eight patients underwent laser-induced interstitial thermotherapy (LITT) for minimally invasive palliative treatment of brain tumours located in eloquent frontal motor regions including the primary motor cortex. A multimodal approach was used to assess the functional outcome of patients after LITT in detail. RESULTS: Following LITT, motor function deteriorated in four patients. In three of these four patients the LITT-induced lesion involved minimal parts of adjacent non-tumorous tissue. By contrast, the other four patients whose LITT-induced signal changes were confined to the tumour, showed no functional deficits. CONCLUSION: These findings support the idea that peri-tumorous neuronal circuitry in motor competent areas may permanently take over those functions that were formerly represented in the neuronal tissue destroyed by the tumour.

Dysfunction of transcallosally mediated motor inhibition and callosal morphology in patients with schizophrenia.

OBJECTIVE: In order to assess the functional integrity of motor pathways through the corpus callosum (CC) in patients with schizophrenia transcallosally mediated inhibition (TI) of voluntary tonic EMG activity of first dorsal interosseus muscle following ipsilateral focal transcranial magnetic stimulation (fTMS) was investigated. In addition thickness and length of CC were calculated. METHOD: Twelve patients suffering from schizophrenia and 12 healthy controls were investigated. CC morphology was measured in mid-sagittal MRI-slices. Latency and duration of TI were calculated. RESULTS: In schizophrenics the duration of TI was significantly prolonged, whereas latencies were not. In addition, a lack of TI was found unilaterally in three patients. Measurements of CC revealed a significantly reduction of the length and thickness in the anterior part of CC in patients. CONCLUSION: These findings indicate that measurement of TI could be used to detect clinical silent affection of transcallosal motor pathways in schizophrenics. The effect of neuroleptic drugs has to be explored.

Effects of riluzole on cortical excitability in patients with amyotrophic lateral sclerosis.

Using transcranial magnetic stimulation, the effect of riluzole (RLZ) on cortical excitability was studied in patients with amyotrophic lateral sclerosis (ALS). Paired-pulse inhibition (PPI) and paired-pulse facilitation (PPF) were reduced. RLZ partially restored deficient PPI in the first of 4 consecutive 3-month periods of testing, but left PPF unchanged. These findings substantiate the view that attenuation of glutamate-related excitotoxicity is an important factor contributing to the beneficial effect of RLZ in ALS.

Tactile apraxia: unimodal apractic disorder of tactile object exploration associated with parietal lobe lesions.

Tactile apraxia is characterized by an isolated disturbance of hand movements for use of and interaction with an object (transitive movements) in the presence of preserved intransitive movements (movements without use of an object, for example repetitive movements or gestures). It is, however, still unclear whether motor and sensory abnormalities represent causal or associated features of tactile apraxia. To address this question, quantitative kinematic recordings of exploratory finger movements (transitive movements) and rapid alternating finger movements (intransitive movements) were studied in 20 healthy volunteers and 22 patients with focal lesions of the parietal, anterofrontal and motor cortex. The most severe deficits of manual object exploration were found in patients with parietal lesions, using the hand contralateral to the lesion. Patients with lesions of the anterior parietal lobe who exhibited prominent sensory deficits and astereognosia showed a decrease in frequency and regularity of exploratory finger movements and a marked increase in exploration space. Patients with posterior parietal lesions exhibiting severe astereognosia, apraxia and deficits in dexterity had a greater decrease in frequency and regularity of manipulative movements, but a less pronounced increase of exploration space than the patients with anterior parietal lesions. Although the patients with parietal lobe lesions could generate rapid alternating finger movements, the regularity of these movements was also impaired. In comparison, patients with frontal lobe lesions exhibited impaired contralesional manipulatory and rapid alternating finger movements but no sensory abnormalities or astereognosia. We conclude that tactile apraxia represents a deficit in the programming of exploratory finger movements mediated by the parietal lobe. The comparison with lesions of other regions participating in the cortical network for tactile exploration reveals that apraxia of exploratory movements in parietal lobe lesions represents a disturbance distinct from elementary motor or sensory abnormalities, but closely related to stereognostic functioning.

Induction of plasticity in the human motor cortex by paired associative stimulation.

Current models of motor cortical plasticity, developed in studies on experimental animals, emphasize the importance of the conjoint activity of somatosensory afferents and intrinsic motor cortical circuits. The hypothesis that an enduring change in excitability in the cortical output circuitry can be induced in the human motor cortex by a paired-stimulation protocol was tested. Low-frequency median nerve stimulation was paired with transcranial magnetic stimulation (TMS) over the optimal cranial site for stimulating the abductor pollicis brevis muscle (APB). This protocol induced an increase in the amplitudes of the motor evoked potentials (MEPs) in the resting APB as well as a prolongation of the silent period measured in the precontracted APB following TMS; amplitudes of MEPs measured in voluntary contraction remained unchanged. Experiments testing the excitability of spinal motoneurons using F-wave studies and electrical stimulation of the brainstem suggested that the site of the plastic changes was within the motor cortex. The increases in resting amplitudes and silent period duration were conditionally dependent on the timing between the afferent and the magnetic stimulation in that they were present when events elicited by afferent and magnetic stimulation were synchronous at the level of the motor cortex. Plasticity induced by paired stimulation evolved rapidly (within 30 min), was persistent (minimum duration 30-60 min) yet reversible, and was topographically specific. This combination of features and the similarity to properties of induced enduring changes in synaptic efficacy, as elucidated in animal studies, leads us to propose that the induced plasticity may represent a signature of associative long-term potentiation of cortical synapses or closely related neuronal mechanisms in the human cortex.

Cutaneomotor integration in humans is somatotopically organized at various levels of the nervous system and is task dependent.

Integration of tactile afferent signals with motor commands is crucial for the performance of purposeful movements such as during manipulation of an object in the hand. To study the somatotopic organization of sensorimotor integration we applied electrical peripheral conditioning stimuli to a digit located near (homotopic stimulation) or distant from (heterotopic stimulation) relaxed or isometrically contracted intrinsic hand muscles at variable time intervals prior to transcranial magnetic stimulation (TMS). Cutaneous stimulation has previously been shown to modulate the amplitude of the motor evoked potential (MEP) and to shorten the duration of the silent period (SP) evoked by TMS. In relaxed target muscles the time-dependent modulation of TMS-evoked motor responses by homotopic conditioning stimulation differed from modulation by heterotopic stimulation. Similar differences in the modulation pattern evoked by homotopic and heterotopic conditioning stimulation were observed for two distinct target muscles of the hand (abductor digiti minimi, abductor pollicis brevis muscle). Differences in modulation were maximal when the conditioning stimulation was applied 25-30 ms and 150-200 ms prior to TMS. Comparison of the modulation of the amplitudes of MEPs evoked by transcranial electrical stimulation (TES) and the modulation of those evoked by TMS suggests that differences between homotopic and heterotopic stimulation originate subcortically at 25- to 30-ms and, at least partially, cortically at 150- to 200-ms interstimulus intervals. In isometrically contracted intrinsic hand muscles the degree to which the SP was shortened reflected the location and the timing of the conditioning stimulus. Shortening was maximal when the conditioning stimulus was applied nearest to the contracted target muscle and 20 ms prior to the test stimulus. In contrast to the SP duration, the MEP size in voluntarily contracted target muscles was unaffected by the location of the conditioning stimulus. The somatotopic gradient of SP shortening was abolished when the two target muscles were simultaneously activated isometrically. Together, our findings suggest that somatotopy of input-output relationships is implemented at both a spinal and a cortical level in the human central nervous system and may also depend on the motor task involved.

Demyelination and axonal degeneration in corpus callosum assessed by analysis of transcallosally mediated inhibition in multiple sclerosis.

OBJECTIVE: Following focal transcranial magnetic cortex stimulation (fTMS), inhibition of voluntary EMG activity in the ipsilateral first dorsal interosseus (FDI) muscle was studied, in order to assess the functional integrity of the corpus callosum in patients with multiple sclerosis (MS). METHODS AND RESULTS: Thirty-four patients suffering from definite MS and 12 healthy, age-matched normal subjects were examined. In mid-sagittal slices, 29 patients showed lesions within the truncus corporis callosi in T2-weighted MRI. In 20 patients, all areas (anterior, middle and posterior parts), in one both the anterior and posterior part, in 3 exclusively the anterior, in 4 the middle and in one the posterior area were affected. In 5 patients, lesions of corpus callosum were lacking. In normal subjects, fTMS elicited a transient inhibition (TI) of preactivated (50% of maximal force) isometric voluntary ipsilateral FDI muscle activity. Mean onset latencies of TI were 35.5+/-5.4 ms in right and 36.1+/-4.2 ms in left FDI. Mean duration of TI amounted to 23.0+/-8.4 ms for right and 24.6+/-8.4 ms for left FDI. In the MS group, TI latencies were significantly increased in 23 and TI durations in 16 cases, whereas a lack of TI was found in 5 patients bilaterally and in 6 unilaterally. In patients, mean onset latencies of TI were 40.4+/-13.8 ms in right and 43.3+/-14.4 ms in left FDI, TI duration amounted to 30.5+/-17.4 ms for right and 31.0+/-25.2 ms for left FDI. Increase of onset latencies and durations of TI were positively correlated with the summed area of lesions of corpus callosum in representative mid-sagittal MRI slices. Significant correlations between TI onset latencies and duration on the one hand, and central motor conduction latencies along corticospinal tracts (CML) on the other hand, were not found. CONCLUSION: The present investigation indicates that measurement of TI elicited by fTMS seems to be a sensitive method for an assessment of demyelination and axonal degeneration within corpus callosum in MS patients.

Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans.

1. Blockade of uptake carriers of gamma-aminobutyric acid (GABA) has been shown to modulate inhibition in cortical slices of experimental animals, although little is known about this mechanism in vivo and, in particular, in humans. 2. The effects of blockade of GABA uptake were studied using transcranial magnetic stimulation (TMS) in humans. In eight healthy volunteers several measures of cortical excitation and inhibition were obtained before and approximately 2 h after ingestion of 5-15 mg of tiagabine (TGB). 3. After TGB ingestion, the duration of the TMS-induced silent period observable in the electromyogram of the voluntarily contracted target muscle was prolonged. Similarly, paired-pulse inhibition of the motor-evoked potential (MEP), as tested by delivering two magnetic shocks of equal suprathreshold intensities at 160 ms interstimulus interval (ISI), was more pronounced. In apparent contradistinction, paired-pulse inhibition of the MEPs produced by a subthreshold conditioning stimulus delivered 3 ms prior to a suprathreshold stimulus was reduced. Paired-pulse facilitation elicited by the same double-shock protocol at an ISI of 10 ms was increased. 4. The prolongation of the GABAB receptor-mediated component of the inhibitory postsynaptic potential observed with TGB in in vitro studies probably underlies the increase in cortical silent period duration. The reduction of the paired-pulse inhibition at 3 ms, in turn, probably reflects inhibition of GABAA receptor-mediated inhibition via presynaptic GABAB receptors. 5. These data provide in vivo evidence of differential modulation of cortical inhibition by blockade of GABA uptake. Presynaptic GABA autoreceptors may be involved in modulating cortical inhibition in the human motor cortex.

Task-dependent modulation of inhibitory actions within the primary motor cortex.

In 11 healthy subjects motor-evoked potentials (MEPs) and silent periods (SPs) were measured in the right first dorsal interosseus (FDI) and abductor pollicis brevis muscles (APB): (1) when transcranial magnetic cortex stimulation (TMS) was applied at tonic isometric contraction of 20% of maximum force, (2) when TMS was applied during tactile exploration of a small object in the hand, (3) when TMS was applied during visually guided goal-directed isometric ramp and hold finger flexion movements, and (4) when at tonic isometric contraction peripheral electrical stimulation (PES) of the median nerve was delivered at various intervals between PES and TMS. Of the natural motor tasks, duration of SPs of small hand muscles was longest during tactile exploration (APB 205+/-42 ms; FDI 213+/-47 ms). SP duration at tonic isometric contraction amounted to 172+/-35 ms in APB and 178+/-31 ms in FDI, respectively. SP duration in FDI was shortest when elicited during visually guided isometric finger movements (159+/-15 ms). At tonic isometric contraction, SP was shortened when PES was applied at latencies -30 to +70 ms in conjunction with TMS. The latter effect was most pronounced when PES was applied 20 ms before TMS. PES-induced effects increased with increasing stimulation strength up to a saturation level which appeared at the transition to painful stimulation strengths. Both isolated stimulation of muscle afferents and of low-threshold cutaneous afferents shortened SP duration. However, PES of the contralateral median nerve had no effect on SPs. Amplitudes of MEPs did not change significantly in any condition. Inhibitory control of motor output circuitries seems to be distinctly modulated by peripheral somatosensory and visual afferent information. We conclude that somatosensory information has privileged access to inhibitory interneuronal circuits within the primary motor cortex.

Multimodal output mapping of human central motor representation on different spatial scales.

1. Non-invasive mapping by focal transcranial magnetic stimulation (TMS) is frequently used to investigate cortical motor function in the intact and injured human brain. We examined how TMS-derived maps relate to the underlying cortical anatomy and to cortical maps generated by functional imaging studies. 2. The centres of gravity (COGs) of TMS maps of the first dorsal intersosseus muscle (FDI) were integrated into 3-D magnetic resonance imaging (MRI) data sets in eleven subjects. In seven of these subjects the TMS-derived COGs were compared with the COG of regional cerebral blood flow increases using positron emission tomography (PET) in an index finger flexion protocol. 3. Mean TMS-derived COG projections were located on the posterior lip of the precentral gyrus and TMS-derived COG projections were in close proximity to the mean PET-derived COG, suggesting that the two methods reflect activity of similar cortical elements. 4. Criteria for a reliable assessment of the COG and the number of positions with a minimum amplitude of two-thirds of the maximum motor-evoked potential (T3Ps) were determined as a function of the number of stimuli and extension of the stimulation field. COGs and T3Ps were compared with an estimate of the size of the human motor cortex targeting alpha-motoneurons of forearm muscles. This comparison suggests that TMS can retrieve spatial information on cortical organization below the macroanatomic scale of cortical regions. 5. Finally, we studied the cortical representation of hand muscles in relation to facial and foot muscle representations and investigated hemispherical asymmetries. We did not find any evidence for a different ipsi- or contralateral representation of the mentalis muscle. Also, no difference was found between FDI representations on the dominant versus the non-dominant hemisphere.

Early-onset multisystem degeneration with central motor, autonomic and optic nerve disturbances: unusual Riley-Day syndrome or new clinical entity?

We report a 21-year-old woman presenting with a slowly progressive tetraparesis, optic nerve atrophy on both sides, and autonomic disturbances since early childhood. The patient has been carefully followed up for 5 years with clinical and ancillary investigations. The results and the time course strongly suggest an underlying degenerative syndrome affecting parts of three major systems: autonomic, motor and visual. Some symptoms resemble familial dysautonomia (FD, Riley-Day syndrome), however, hallmarks of FD, such as absence of fungiform papillae of the tongue, abnormal reaction on intradermal histamine injection, absent tendon reflexes, are missing, and central motor disturbances have not been described in FD. We consider this syndrome a slowly progressive multisystemic degeneration with two unusual hitherto unreported features: the combination of affected systems (autonomic and motor systems, optic nerves), and the early onset.

Somatosensory evoked potentials modified by laser-induced lesions of the rat cortex.

The effect of focal application of laser energy on the modification of somatosensory evoked potentials (SEPs) was studied in sensory cortical fields of the rat. This article describes the methodological set-up for recording of SEPs and for determining location and size of the laser-induced lesion. The results show that both the size of the lesion of the somatosensory cortex, and the suppression and time of recovery of cortical SEPs varied depending on the laser energy dose. It remains to be analyzed by further experiments if the recovery of SEPs is due to a transient dysfunction of the somatosensory cortex or if it reflects cortical plasticity.

Parallel and serial processing of haptic information in man: effects of parietal lesions on sensorimotor hand function.

Recent animal studies have shown that there is an evolutionary shift within the order of primates from parallel to serial processing of haptic information. In an attempt to determine whether there is also evidence of serial processing in humans 10 patients with parietal cortical lesions, three patients with subcortical lesions and one patient after hemispherectomy, were examined. Case-by-case and across subject analysis of lesion type, sensorimotor profile and electrophysiological findings showed that in unihemispheric lesions: (a) there is little impairment of thermesthesia, nociception and vibration sense: (b) two-point discrimination and integrity of the N20 somatosensory component are highly correlated; (c) a loss of the N20 component is accompanied by a severe impairment of stereognosis; (d) conversely, in more posterior lesions astereognosis can occur with an intact N20 component; and (e) if the lesion is in the right hemisphere there is frequently impairment of graphesthesia in both hands. These data are taken to indicate serial processing from SI (as evidenced by an intact N20 component) to posterior parietal cortex allowing progressive spatial and temporal integration. In graphesthesia our data suggest an integrative function of the right parietal cortex for both sides of the body. Other sensory qualities like vibration nociception and thermesthesia are apparently processed in a non-serial, probably parallel way involving both hemispheres. The effects of cerebral lesions in our series suggest parallel as well as serial processing of somesthetic information in man underlying the perception of different haptic features.

Subcortical origin of visuomotor apraxia.

Visuomotor apraxia (VMA) is a clinical syndrome characterized by a failure to make use of visual information when performing a target-directed movement. Visuomotor apraxia has traditionally been assumed to result from a disconnection of cortico-cortical fibres between visual and motor areas following occipito-parietal lesions. We describe a patient who developed a permanent contralesional and a temporary ipsilesional visuomotor apraxia as part of a complex neurological syndrome after a right [corrected] thalamic haemorrhage. MRI showed that the suprathalamic white matter was not involved but the most caudal fibres of the internal capsule appeared to be interrupted. To our knowledge this is the first case of a VMA with a lesion restricted to a deep subcortical area indicating that VMA can result from damage to subcortical projections rather than interruption of cortico-cortical fibres.

Somatosensory evoked potentials elicited by intraneural microstimulation of afferent nerve fibers.

Cortical somatosensory evoked potentials (SEPs) after intraneural microstimulation (IMS) of cutaneous and afferent muscle nerve fibers in the median nerve were recorded to study the contribution of different afferent fiber groups to the SEP. Thirty-seven cutaneous fiber bundles, 10 afferent muscle nerve fiber bundles, and 45 single mechanoreceptive afferents of FA I- (n = 12), FA II- (n = 8), SA I- (n = 13), and SA II-type (n = 12) were studied in 29 healthy subjects. IMS of cutaneous fiber bundles evoked cortical responses corresponding to the N20 component after median nerve stimulation in 86% of the fascicles studied, whereas IMS of muscle nerve fiber bundles elicited responses only in 20%. After IMS of single mechanoreceptive afferents of FA I-, FA II-, and SA I-type cortical responses were obtained in all groups in approximately 80% of the stimulated units. The latencies of the SEPs evoked by IMS were comparable to that after compound median nerve stimulation (mean difference 0.58 ms). The N20 amplitudes of SEPs after IMS of cutaneous fiber bundles were on average 28% (n = 32) and for single afferents 22% (n = 30) of that after compound nerve stimulation. It is concluded that the median nerve SEPs evoked by compound median nerve stimulation of the resting hand are dominated by cutaneous rather than muscle afferent input. Furthermore, the fact that selective stimulation of only a few cutaneous afferents produces cortical SEPs of rather high amplitude is compatible with the view that sensory information produced by selective afferent stimulation is differentially gated into the somatosensory cortex.

Altered force release control in Parkinson's disease.

Isometric force tracking and force aiming modified by visual feed-back was investigated in Parkinsonian (PD) and control subjects. Production and maintenance of isometric force, production and release of isotonic force, and maximum force were tested. Statistical analysis revealed that the PD patients could perform most force tasks in a similar manner to that of control subjects. However, PD patients had difficulties in sustaining target force over a 30-s period and in performing rapid alternating movements. The major finding in PD patients was an inability to precisely release a target force. Overall these data suggest that the release of a produced force is a sensitive motor control parameter in Parkinson's disease.