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Joseph Classen

Publications and source records attributed to Joseph Classen.

17 recordsLinked to original sources
PubMed2007

Characteristics of sensory trick-like manoeuvres in jaw-opening dystonia.

We evaluated the effect of different manipulations on the performance of a standardized counting task in 7 patients with idiopathic jaw-opening dystonia. Patients used a small stick as sensory stimulus. Following conditions were examined: stick placed between teeth and cheek (CHEEK), biting on stick (TEETH), voluntary jaw occlusion without stick (OCCLUSION). Articulation was rated by patients and experimenters and surface electromyographic activity (EMG) was recorded. Patient-rating (CHEEK - 36.6%, TEETH - 48.1%) and EMG (-18.1%; -17.3%) were significantly improved for conditions using the stick, whereas experimenter-rating showed a trend for TEETH (-16.2%). Although jaw occlusion during speaking deteriorates articulation in healthy subjects, there was no further deterioration in patients and EMG was even significantly reduced (-18.6%). Comparable results were obtained in 1 patient using a special dental device. We conclude that sensory tricks significantly improve subjective and objective parameters. Besides tactile stimulation, altered proprioceptive feedback and antagonist activation may modulate hyperactive dystonic networks.

Analysis of Variance↗
PubMed2006

Modular organization of finger movements by the human central nervous system.

The motor system may generate automated movements, such as walking, by combining modular spinal motor synergies. However, it remains unknown whether a modular neuronal architecture is sufficient to generate the unique flexibility of human finger movements, which rely on cortical structures. Here we show that finger movements evoked by transcranial magnetic stimulation (TMS) of the primary motor cortex reproduced distinctive features of the spatial representation of voluntary movements as identified in previous neuroimaging studies, consistent with naturalistic activation of neuronal elements. Principal component analysis revealed that the dimensionality of TMS-evoked movements was low. Principal components extracted from TMS-induced finger movements resembled those derived from end-postures of voluntary movements performed to grasp imagined objects, and a small subset of them was sufficient to reconstruct these movements with remarkable fidelity. The motor system may coordinate even the most dexterous movements by using a modular architecture involving cortical components.

Adult↗
PubMed2006

The two sides of associative plasticity in writer's cramp.

Neuronal plasticity is to be kept within operational limits to serve its purpose as a safe memory system that shapes and focuses sensory and motor representations. Temporal and spatial properties of motor cortical plasticity were assessed in patients with writer's cramp using a model of long-term potentiation (LTP) and long-term depression (LTD) of synaptic efficacy. Paired associative stimulation (PAS) combined repetitive electric stimulation of the median or ulnar nerve (MN or UN) with subsequent transcranial magnetic stimulation of the contralateral dominant motor cortex at 21.5 ms (MN-PAS21.5; UN-PAS21.5) or 10 ms (MN-PAS10). Motor-evoked potentials were recorded from abductor pollicis brevis (APB) muscle and abductor digiti minimi (ADM) muscles in 10 patients with writer's cramp and 10 matched healthy control subjects. Following MN-PAS21.5 or UN-PAS21.5 in non-dystonic subjects, motor responses increased if the afferent PAS-component came from a homologous peripheral region and remained stable with a non-homologous input. In contrast, following either MN-PAS21.5 or UN-PAS21.5, both APB- and ADM-amplitudes increased in patients. Compared with controls, this increase started earlier, its magnitude was larger and its duration longer. Following MN-PAS10 in controls, APB-amplitudes decreased, while ADM-amplitudes increased. In writer's cramp, the decrease of APB-amplitudes started earlier and lasted longer. Of note, ADM-amplitudes were decreased, too. LTP-like as well as LTD-like plasticity is abnormal with respect to both gain and spatial organization. These findings may help to develop a pathophysiological model explaining core features of focal dystonia.

Adult↗
PubMed2005

Formation of a motor memory by action observation.

Mirror neurons discharge with both action observation and action execution. It has been proposed that the mirror neuron system is instrumental in motor learning. The human primary motor cortex (M1) displays mirror activity in response to movement observation, is capable of forming motor memories, and is involved in motor learning. However, it is not known whether movement observation can lead directly to the formation of motor memories in the M1, which is considered a likely physiological step in motor learning. Here, we used transcranial magnetic stimulation (TMS) to show that observation of another individual performing simple repetitive thumb movements gives rise to a kinematically specific memory trace of the observed motions in M1. An extended period of observation of thumb movements that were oriented oppositely to the previously determined habitual directional bias increased the probability of TMS-evoked thumb movements to fall within the observed direction. Furthermore, the acceleration of TMS-evoked thumb movements along the principal movement axis and the balance of excitability of muscle representations active in the observed movements were altered in favor of the observed movement direction. These findings support a role for the mirror neuron system in memory formation and possibly human motor learning.

Adult↗
PubMed2005

Encoding a motor memory in the older adult by action observation.

The ability of motor training to encode a motor memory is reduced in older adults. Here, we tested the hypothesis that training-dependent memory encoding, an issue of relevance in neurorehabilitation, is enhanced in elder individuals by action observation which alone can contribute to learning processes. A group of 11 healthy older adults participated in this study, which consisted of three randomized counterbalanced sessions on different days testing the effects of motor training (MT) alone, action observation (AO) alone, and a combination of both (MT + AO) on motor memory encoding. The combination of MT + AO formed a motor memory in the primary motor cortex and differentially modulated motor cortical excitability in muscles that were agonist and antagonist with respect to the training task, but MT or AO alone did not. These results suggest that action observation can enhance the effects of motor training on memory encoding protocols in the older adult, possibly through Hebbian modulation of intracortical excitatory mechanisms.

Aged↗
PubMed2005

Temporary occlusion of associative motor cortical plasticity by prior dynamic motor training.

A novel Hebbian stimulation paradigm was employed to examine physiological correlates of motor memory formation in humans. Repetitive pairing of median nerve stimulation with transcranial magnetic stimulation over the contralateral motor cortex (paired associative stimulation, PAS) may decrease human motor cortical excitability at interstimulus intervals of 10 ms (PAS10) or increase excitability at 25 ms (PAS25). The properties of this plasticity have previously been shown to resemble associative timing-dependent long-term depression (LTD) and long-term potentiation (LTP) as established in vitro. Immediately after training a novel dynamic motor task, the capacity of the motor cortex to undergo plasticity in response to PAS25 was abolished. PAS10-induced plasticity remained unchanged. When retested after 6 h, PAS25-induced plasticity recovered to baseline levels. After training, normal PAS25-induced plasticity was observed in the contralateral training-naive motor cortex. Motor training did not reduce the efficacy of PAS25 to enhance cortical excitability when PAS10 was interspersed between the training and application of the PAS25 protocol. This indicated that the mechanism supporting PAS25-induced plasticity had remained intact immediately after training. Behavioral evidence was obtained for continued optimization of force generation at a time when PAS25-induced plasticity was blocked in the training motor cortex. Application of the PAS protocols after motor training did not prevent the consolidation of motor skills evident as performance gains at later retesting. The results are consistent with a concept of temporary suppression of associative cortical plasticity by neuronal mechanisms involved in motor training. Although it remains an open question exactly which element of motor training was responsible for this effect, our findings may link dynamic properties of LTP formation, as established in animal experiments, with human motor memory formation and possibly dynamic motor learning.

Adult↗
PubMed2005

Timing-dependent plasticity in human primary somatosensory cortex.

Animal experiments suggest that cortical sensory representations may be remodelled as a consequence of changing synaptic efficacy by timing-dependent associative neuronal activity. Here we describe a timing-based associative form of plasticity in human somatosensory cortex. Paired associative stimulation (PAS) was performed by combining repetitive median nerve stimulation with transcranial magnetic stimulation (TMS) over the contralateral postcentral region. PAS increased exclusively the amplitude of the P25 component of the median nerve-evoked somatosensory-evoked potential (MN-SSEP), which is probably generated in the superficial cortical layers of area 3b. SSEP components reflecting neuronal activity in deeper cortical layers (N20 component) or subcortical regions (P14 component) remained constant. PAS-induced enhancement of P25 amplitude displayed topographical specificity both for the recording (MN-SSEP versus tibial nerve-SSEP) and the stimulation (magnetic stimulation targeting somatosensory versus motor cortex) arrangements. Modulation of P25 amplitude was confined to a narrow range of interstimulus intervals (ISIs) between the MN pulse and the TMS pulse, and the sign of the modulation changed with ISIs differing by only 15 ms. The function describing the ISI dependence of PAS effects on somatosensory cortex resembled one previously observed in motor cortex, shifted by approximately 7 ms. The findings suggest a simple model of modulation of excitability in human primary somatosensory cortex, possibly by mechanisms related to the spike-timing-dependent plasticity of neuronal synapses located in upper cortical layers.

Adult↗
PubMed2004

Modulation of associative human motor cortical plasticity by attention.

The role of attention in generating motor memories remains controversial principally because it is difficult to separate the effects of attention from changes in kinematics of motor performance. We attempted to disentangle attention from performance effects by varying attention while plasticity was induced in human primary motor cortex by external stimulation in the absence of voluntary movement. A paired associative stimulation (PAS) protocol was employed consisting of repetitive application of single afferent electric stimuli, delivered to the right median nerve, paired with single-pulse transcranial magnetic stimulation (TMS) over the optimal site for activation of the right abductor pollicis brevis muscle (APB) to generate near-synchronous events in the left primary motor cortex. In experiment 1, the spatial location of attention was varied. PAS failed to induce plasticity when the subject's attention was directed to their left hand, away from the right target hand the cortical representation of which was being stimulated by PAS. In experiment 2, the grade of attention to the target hand was manipulated. PAS-induced plasticity was maximal when the subject viewed their target hand, and its magnitude was slightly reduced when the subject could only feel their hand. Conversely, plasticity was completely blocked when the subject's attention was diverted from the target hand by a competing cognitive task. A similar modulation by attention was observed for PAS-induced changes in the duration of the silent period evoked by TMS in voluntarily contracted muscle. Associative plasticity in the human motor cortex depends decisively on attention.

Adult↗
PubMed2004

Measurements of transcallosally mediated cortical inhibition for differentiating parkinsonian syndromes.

Clinicopathologic evidence suggests differential involvement of cortex and corpus callosum (CC) in various disorders presenting with a parkinsonian syndrome. We tested the hypothesis of whether neurophysiologic and morphometric assessments of CC as surrogate parameters of cortical involvement could be helpful in differential diagnosis of parkinsonian disorders. The integrity of CC was assessed neurophysiologically by measuring the ipsilateral silent period (iSP) evoked by transcranial magnetic stimulation (TMS) in a total of 25 patients with idiopathic parkinsonian syndromes (IPS), corticobasal ganglionic degeneration (CBD), progressive supranuclear palsy (PSP), or multiple system atrophy (MSA). Additionally, morphometric analyses of magnetic resonance imaging (MRI) measurements of CC was carried out in all patients. iSP was abnormal in all 5 CBD and all 5 PSP patients, whereas it was intact in all 10 IPS patients and all 5 MSA patients. Among various MRI parameters of CC, testing between different groups revealed a significant difference only for measurements of the middle part of the truncus. CBD and PSP patients exhibited a significant atrophy as compared with control subjects. These data suggest impairment of callosal integrity in patients with CBD and PSP. iSP measurements may be a useful clinical neurophysiologic test in differential diagnosis of patients with parkinsonian syndromes.

Aged↗
PubMed2004

Paired associative stimulation.

Paired associative stimulation (PAS) refers to a paradigm consisting of slow-rate repetitive low-frequency median nerve stimulation combined with transcranial magnetic stimulation (TMS) over the contralateral motor cortex. This protocol has been shown to induce plastic changes of excitability in the human motor cortex. Its principles of design were shaped after associative long-term potentiation (LTP) in experimental animals, a cellular mechanism likely to be relevant for learning and memory. PAS-induced changes of cortical excitability share a number of physiological properties with LTP. Of particular importance is the fact that the sign of PAS-induced changes of the size of amplitudes of the motor evoked potentials (MEPs) depends on the exact interval between the afferent and the magnetic pulse during the intervention. A number of observations suggest that PAS-induced excitability changes may have functional significance. PAS-induced plasticity may contribute to elucidating the pathogenesis of neurological disorders where neuroplasticity is thought to have a pathogenetic role. Finally, PAS-induced plasticity may itself have therapeutic potential.

Animals↗
PubMed2003

A temporally asymmetric Hebbian rule governing plasticity in the human motor cortex.

Synaptic plasticity is conspicuously dependent on the temporal order of the pre- and postsynaptic activity. Human motor cortical excitability can be increased by a paired associative stimulation (PAS) protocol. Here we show that it can also be decreased by minimally changing the interval between the two associative stimuli. Corticomotor excitability of the abductor pollicis brevis (APB) representation was tested before and after repetitively pairing of single right median nerve simulation with single pulse transcranial magnetic stimulation (TMS) delivered over the optimal site for activation of the contralateral APB. Following PAS, depression of TMS-evoked motor-evoked potentials (MEPs) was induced only when the median nerve stimulation preceded the TMS pulse by 10 ms, while enhancement of cortical excitability was induced using an interstimulus interval of 25 ms, suggesting an important role of the sequence of cortical events triggered by the two stimulation modalities. Experiments using F-wave studies and electrical brain stem stimulation indicated that the site of the plastic changes underlying the decrease of MEP amplitudes following PAS (10 ms) was within the motor cortex. MEP amplitudes remained depressed for approximately 90 min. The decrease of MEP amplitudes was blocked when PAS(10 ms) was performed under the influence of dextromethorphan, an N-methyl-d-aspartate-receptor antagonist, or nimodipine, an L-type voltage-gated calcium-channel antagonist. The physiological profile of the depression of human motor cortical excitability following PAS(10 ms) suggests long-term depression of synaptic efficacy to be involved. Together with earlier findings, this study suggests that strict temporal Hebbian rules govern the induction of long-term potentiation/long-term depression-like phenomena in vivo in the human primary motor cortex.

Adolescent↗
PubMed2002

Reduced inhibition within primary motor cortex in patients with poststroke focal motor seizures.

BACKGROUND: Following an ischemic brain lesion, the affected cortex undergoes structural and functional changes that may lead to increased cortical excitability or decreased inhibitory neuronal activity, resulting in the occurrence of poststroke epileptic seizures in 6 to 10% of patients with stroke. METHODS: To assess motor cortical excitability, transcranial magnetic stimulation (TMS) was used to determine the silent period (SP) duration in 84 consecutive patients with ischemic stroke. RESULTS: In a subpopulation of six patients (38 to 72 years old) a significant decrease of the SP duration (mean 116 +/- 14 msec) was detected in either the arm or the leg on the affected side as compared to the corresponding unaffected limb (mean 231 +/- 32 msec). This electrophysiologic abnormality was clinically associated with focal motor seizures in five of the six patients, whereas none of the other 76 patients with normal or prolonged SP durations developed seizures or epilepsy. CONCLUSIONS: Silent period shortening in this group reflects decreased inhibitory activity that may partly be related to functional or structural impairment of GABAergic interneurons. TMS may be of value for determining patients with stroke at risk for developing poststroke seizures.

Adult↗
PubMed2002

Mechanisms of enhancement of human motor cortex excitability induced by interventional paired associative stimulation.

Associative stimulation has been shown to enhance excitability in the human motor cortex (Stefan et al. 2000); however, little is known about the underlying mechanisms. An interventional paired associative stimulation (IPAS) was employed consisting of repetitive application of single afferent electric stimuli, delivered to the right median nerve, paired with single pulse transcranial magnetic stimulation (TMS) over the optimal site for activation of the abductor pollicis brevis muscle (APB) to generate approximately synchronous events in the primary motor cortex. Compared to baseline, motor evoked potentials (MEPs) induced by unconditioned, single TMS pulses increased after IPAS. By contrast, intracortical inhibition, assessed using (i) a suprathreshold test TMS pulse conditioned by a subthreshold TMS pulse delivered 3 ms before the test pulse, and (ii) a suprathreshold test TMS pulse conditioned by afferent median nerve stimulation delivered 25 ms before the TMS pulse, remained unchanged when assessed with appropriately matching test stimulus intensities. The increase of single-pulse TMS-evoked MEP amplitudes was blocked when IPAS was performed under the influence of dextromethorphan, an N-methyl-D-aspartate (NMDA) receptor antagonist known to block long-term potentiation (LTP). Further experiments employing the double-shock TMS protocol suggested that the afferent pulse, as one component of the IPAS protocol, induced disinhibition of the primary motor cortex at the time when the TMS pulse, as the other component of IPAS, was delivered. Together, these findings support the view that LTP-like mechanisms may underlie the cortical plasticity induced by IPAS.

Adult↗
PubMed2002

Modulation of use-dependent plasticity by d-amphetamine.

Use-dependent plasticity, thought to contribute to functional recovery after brain injury, is elicited by motor training. The purpose of this study was to determine if administration of d-amphetamine facilitates the effects of motor training on use-dependent plasticity. Healthy human volunteers underwent a training period of voluntary thumb movements under the effects of placebo or d-amphetamine in different sessions in a randomized double-blind, counterbalanced design. Previous work in a drug-naive condition showed that such training causes changes in the direction of thumb movements evoked by transcranial magnetic stimulation and in transcranial magnetic stimulation-evoked electromyographic responses. The endpoint measure of the study was the magnitude of training-induced changes in transcranial magnetic stimulation-evoked kinematic and electromyographic responses in the d-amphetamine and in the placebo conditions. Motor training resulted in increased magnitude, faster development and longer lasting duration of use-dependent plasticity under d-amphetamine compared to the placebo session. These results document a facilitatory effect of d-amphetamine on use-dependent plasticity, a possible mechanism mediating the beneficial effect of this drug on functional recovery after cortical lesions.

Adult↗