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H R Siebner

Publications and source records attributed to H R Siebner.

At least 19 recordsLinked to original sources

Voxel-based morphometry shows no decreases in cerebellar gray matter volume in essential tremor.

OBJECTIVE: To investigate cerebellar gray matter volume in patients with essential tremor (ET). METHODS: We used voxel-based morphometry (VBM) based on high-resolution T1-weighted MRI to compare gray and white matter density between 27 patients with ET and 27 age- and sex-matched healthy control subjects. Fourteen patients had only postural tremor, whereas 13 patients showed additional intention tremor. RESULTS: VBM failed to demonstrate regional decreases in gray and white matter volume in patients with ET. There was, however, an expansion in gray matter depending on the type of tremor. Compared with age-matched control groups, patients with intention tremor showed a relative expansion of gray matter bilaterally in the region of the temporoparietal junction and the right middle occipital cortex. CONCLUSIONS: The lack of a consistent decrease in gray and white matter density argues against a progressive neurodegenerative process in essential tremor that leads to a substantial decrease in cerebellar gray matter volume. Patients with predominant intention tremor show a relative expansion of gray matter areas involved in higher order visuospatial processing, which might represent a long-term result of adaptive reorganization compensating the higher demands on the visuospatial control of skilled movements in case of trembling.

Adult↗

Observation of a finger or an object movement primes imitative responses differentially.

Behavioural advantages for imitation of human movements over movements instructed by other visual stimuli are attributed to an 'action observation-execution matching' (AOEM) mechanism. Here, we demonstrate that priming/exogenous cueing with a videotaped finger movement stimulus (S1) produces specific congruency effects in reaction times (RTs) of imitative responses to a target movement (S2) at defined stimulus onset asynchronies (SOAs). When contrasted with a moving object at an SOA of 533 ms, only a human movement is capable of inducing an effect reminiscent of 'inhibition of return' (IOR), i.e. a significant advantage for imitation of a subsequent incongruent as compared to a congruent movement. When responses are primed by a finger movement at SOAs of 533 and 1,200 ms, inhibition of congruent or facilitation of incongruent responses, respectively, is stronger as compared to priming by a moving object. This pattern does not depend on whether S2 presents a finger movement or a moving object, thus effects cannot be attributed to visual similarity between S1 and S2. We propose that, whereas both priming by a finger movement and a moving object induces processes of spatial orienting, solely observation of a human movement activates AOEM. Thus, S1 immediately elicits an imitative response tendency. As an overt imitation of S1 is inadequate in the present setting, the response is inhibited which, in turn, modulates congruency effects.

Adult↗

The basal ganglia are hyperactive during the discrimination of tactile stimuli in writer's cramp.

Writer's cramp is a focal hand dystonia that specifically affects handwriting. Though writer's cramp has been attributed to a dysfunction of the basal ganglia, the role of the basal ganglia in the pathogenesis of writer's cramp remains to be determined. Seventeen patients with writer's cramp (nine females; age range: 24-71 years) and 17 healthy individuals (six females; age range: 27-68 years) underwent functional MRI (fMRI) while they discriminated the orientation of gratings delivered to the tip of the right index finger. Statistical parametric mapping was used to analyse the fMRI data. The significance level was set at a corrected P-value of 0.05. Relative to healthy controls, patients with writer's cramp showed a widespread bilateral increase in task-related activity in the putamen, caudate nucleus, internal globus pallidus and lateral thalamus. In these areas, hyperactivity was more pronounced in patients who had recently developed writer's cramp. The enhanced response of the basal ganglia to tactile input from the affected hand is compatible with the concept of impaired centre-surround inhibition within the basal ganglia-thalamic circuit and may lead to an excessive activation of sensorimotor cortical areas during skilled movements affected by dystonia. Outside the basal ganglia, dystonic patients showed task-related overactivity in visual cortical areas, left anterior insula and right intraparietal sulcus, but not in the primary or secondary sensory cortex. In addition, task-related activity in the cerebellar nuclei, posterior vermis, right paramedian cerebellar hemisphere and dorsal pons was inversely related with the severity of hand dystonia. Regional activity in these areas may reflect secondary adaptive reorganization at the systems level to compensate for the dysfunction in the basal ganglia-thalamic loop.

Adult↗

Hemispheric asymmetry and somatotopy of afferent inhibition in healthy humans.

A conditioning electrical stimulus to a digital nerve can inhibit the motor-evoked potentials (MEPs) in adjacent hand muscles elicited by transcranial magnetic stimulation (TMS) to the contralateral primary motor cortex (M1) when given 25-50 ms before the TMS pulse. This is referred to as short-latency afferent inhibition (SAI). We studied inter-hemispheric differences (Experiment 1) and within-limb somatotopy (Experiment 2) of SAI in healthy right-handers. In Experiment 1, conditioning electrical pulses were applied to the right or left index finger (D2) and MEPs were recorded from relaxed first dorsal interosseus (FDI) and abductor digiti minimi (ADM) muscles ipsilateral to the conditioning stimulus. We found that SAI was more pronounced in right hand muscles. In Experiment 2, electrical stimulation was applied to the right D2 and MEPs were recorded from ipsilateral FDI, extensor digitorum communis (EDC) and biceps brachii (BB) muscles. The amount of SAI did not differ between FDI, EDC and BB muscles. These data demonstrate inter-hemispheric differences in the processing of cutaneous input from the hand, with stronger SAI in the dominant left hemisphere. We also found that SAI occurred not only in hand muscles adjacent to electrical digital stimulation, but also in distant hand and forearm and also proximal arm muscles. This suggests that SAI induced by electrical D2 stimulation is not focal and somatotopically specific, but a more widespread inhibitory phenomenon.

Adult↗

Reduced sensorimotor inhibition in the ipsilesional motor cortex in a patient with chronic stroke of the paramedian thalamus.

OBJECTIVE: Unilateral or bilateral paramedian infarction in the region of the thalamus and upper midbrain may lead to hypersomnia. To determine whether unilateral infarction of the paramedian thalamus leads to changes in excitability of ipsilesional primary motor hand area (M1). METHODS: We describe a patient with chronic stroke of the right dorsomedian and intralaminar thalamic nuclei, who suffered from mild persistent hypersomnia. We studied the excitability of the right and left M1 with transcranial magnetic stimulation (TMS) in the patient, and in 10 healthy controls. RESULTS: In contrast to healthy controls, contralateral electrical stimulation of the median nerve failed to induce short-latency afferent inhibition (SAI) in the ipsilesional M1. Other measures of corticomotor excitability and somatosensory evoked potentials were normal. CONCLUSIONS: The selective loss of ipsilateral SAI in a patient with paramedian thalamic stroke suggests that during wakefulness, the intact paramedian thalamus facilitates the excitability of intracortical inhibitory circuits, which process thalamocortical sensory inputs in the ipsilateral M1. This preliminary finding suggests that measurements of SAI may provide a means of probing the integrity of some neural pathways, which are involved in the control of wakefulness and arousal. SIGNIFICANCE: In addition to the established role of the paramedian thalamus in arousal and memory, our observation suggests that thalamocortical projections from the paramedian thalamus contribute to the integration of sensory input at the cortical level during wakefulness.

Adult↗

Effect of bilateral subthalamic nucleus stimulation on balance and finger control in Parkinson's disease.

We aimed to quantify the effects of bilateral subthalamic nucleus (STN) stimulation in Parkinson's disease (PD) on stance and gait ("axial"motor control), and related this to effects on finger movements ("appendicular" motor control). Fourteen PD patients and 20 matched controls participated. Subjects completed several balance and gait tasks (standing with eyes open or closed, on a normal or foam surface; retropulsion test; walking with eyes closed; walking up and down stairs; Get Up and Go test). Postural control was quantified using trunk sway measurements (angle and angular velocity) in the roll and pitch directions. Subjects further performed a pinch grip reaction time task, where we measured isometric grip forces, as well as movement and reaction times. Patients were examined with STN stimulators switched on or off (order randomised across patients), always after a supramaximal levodopa dosage. STN stimulation improved postural control, as reflected by a reduced trunk sway tremor during stance, a reduced duration for all gait tasks, an increased trunk pitch velocity while rising from a chair, and improved roll stability. STN stimulation also improved finger control, as reflected by a reduced time to reach maximum grip force, without altering reaction times and maximum force levels. Improvements in finger control timing did not correlate with reduced task durations during gait. We conclude that STN stimulation affords improvement of postural control in PD, over and above optimal drug treatment. STN stimulation also provides a simultaneous effect on distal and axial motor control. Because improvements in distal and axial motor control were not correlated, we assume that these effects are mediated by stimulation of different structures within the STN.

Adult↗

Dopaminergic drugs restore facilitatory premotor-motor interactions in Parkinson disease.

OBJECTIVE: To explore the impact of dopaminergic therapy on facilitatory premotor-motor interactions in patients with Parkinson disease (PD). METHODS: Ten patients with PD and 10 age-matched healthy volunteers received repetitive transcranial magnetic stimulation (rTMS) over the left dorsal premotor cortex (5 Hz, 1,500 stimuli, 90% of active motor threshold). Patients were studied while "on" and "off" medication. Motor evoked potentials (MEPs) were recorded from the right first dorsal interosseus muscle before and after rTMS to quantify changes in motor cortical excitability. The after-effects of rTMS on motor function were assessed using the Unified Parkinson's Disease Rating Scale and the kinematics of ballistic wrist flexions. RESULTS: MEPs evoked from the ipsilateral motor cortex were increased after premotor rTMS in relaxed normal subjects, consistent with an increase in motor cortex excitability. In patients with PD, the effect of premotor rTMS was modified by medication. When patients were in a practically defined "off" state, premotor rTMS had no effect on MEPs, whereas when they were in the "on" state, premotor rTMS facilitated MEPs. Premotor rTMS had no effect on clinical parkinsonian symptoms or motor performance of ballistic wrist movements, regardless of whether patients were in the "on" or "off" state. CONCLUSIONS: In Parkinson disease, the ability of premotor-motor connections to increase motor cortical excitability is defective but restored to normal by dopaminergic medication. Dopamine deficiency in the basal ganglia may affect the way that frontal motor areas interact with each other.

Adult↗

Motor reorganization in asymptomatic carriers of a single mutant Parkin allele: a human model for presymptomatic parkinsonism.

Mutations in the Parkin gene are the most common known single cause of early-onset parkinsonism. It has been shown that asymptomatic carriers with a single mutant allele have latent presynaptic dopaminergic dysfunction in the striatum. Here we used functional MRI to map movement-related neuronal activity during internally selected or externally determined finger movements in 12 asymptomatic carriers of a Parkin mutation and 12 healthy non-carriers. Mean response times were 63 ms shorter during internally selected movements than during externally guided movements (P = 0.003). There were no differences in mean response times between groups (P > 0.2). Compared with externally determined movements, the internal selection of movements led to a stronger activation of rostral motor areas, including the rostral cingulate motor area (rCMA), rostral supplementary motor area, medial and dorsolateral prefrontal cortices. The genotype had a significant impact on movement-related activation patterns. Asymptomatic carriers showed a stronger increase in movement-related activity in the right rCMA and left dorsal premotor cortex, but only if movements relied on internal cues. In addition, synaptic activity in the rCMA had a stronger influence on activity in the basal ganglia in the context of internally selected movements in asymptomatic carriers relative to non-carriers. We infer that this reorganization of striatocortical motor loops reflects a compensatory effort to overcome latent nigrostriatal dysfunction.

Adult↗

Abnormal excitability of premotor-motor connections in de novo Parkinson's disease.

The dorsal premotor cortex (PMd) is abnormally active in patients with idiopathic Parkinson's disease. This has been interpreted as a functional correlate of adaptive plasticity within the motor system to compensate for deficient activation of striato-mesial-frontal projections in these patients. Whether abnormal PMd activity influences excitability in the primary motor cortex (M1) in untreated Parkinson's disease patients and how this premotor-motor interaction might be altered by l-dopa is unclear. To this end, we studied the effects of 1 Hz premotor repetitive transcranial magnetic stimulation (rTMS) on M1 excitability in 10 previously untreated non-tremulous Parkinson's disease patients before (day 1) and after (day 8) their first ever l-dopa treatment and compared the results with those of a group of nine age- and sex-matched healthy controls. In each rTMS session, 1200 pulses of 1 Hz rTMS were applied at an intensity of 80% active motor threshold (AMT) to the PMd contralateral to the clinically more affected side in Parkinson's disease patients and to the left PMd in healthy controls. Intracortical paired pulse excitability of ipsilateral M1 was probed using a TMS paired pulse paradigm where subthreshold conditioning pulses (80% of AMT) were given 2-15 ms prior to a suprathreshold test pulse. In Parkinson's disease patients, abnormal baseline intracortical excitability at an interstimulus interval (ISI) of 5 ms was normalized by premotor rTMS. In contrast, rTMS led to an increased excitability at an ISI of 5 ms in healthy controls. Premotor rTMS effects lasted longer (for at least a week) in patients. These results show that the modifiability of premotor-motor connections is abnormal in untreated Parkinson's disease. A single dose of l-dopa reversed, i.e. normalized, the direction of excitability changes in M1 following premotor rTMS in Parkinson's disease patients, suggesting that dopamine depletion directly or indirectly influences premotor-motor interactions in Parkinson's disease. The rTMS conditioning approach described here provides a promising tool to delineate further the excitability changes in frontal motor areas in response to progressive degeneration of nigrostriatal dopaminergic neurons and also to chronic l-dopa treatment in Parkinson's disease.

Adult↗

Inhibitory interactions between pairs of subthreshold conditioning stimuli in the human motor cortex.

OBJECTIVE: These experiments examined short interval paired-pulse paradigms for intracortical inhibition (ICI) and facilitation (ICF). We tested whether pairs of subthreshold conditioning stimuli interact, and whether they showed rapid periodicity similar to that observed in subthreshold I-wave interaction. METHODS: Transcranial magnetic stimulation (TMS) was given over left M1 to evoke a motor-evoked potential (MEP) of approximately 1 mV peak-to-peak amplitude in the contralateral first dorsal interosseous (FDI) muscle. Each test shock (TS) was preceded by single or paired subthreshold conditioning stimuli (CS(1) and CS(2)) at short interstimulus intervals (ISIs 1-15 ms). Intensities of CS were set just below thresholds for intracortical inhibition (ICI) or intracortical facilitation (ICF). RESULTS: Each CS(single) alone had no effect on the test MEP, but with two CS, clear inhibition was elicited at certain intervals. With a CS(2)-TS interval of 2 ms, maximum suppression occurred if CS(1) was applied 1-2.5 ms before CS(2). This inhibitory effect tapered off gradually as the CS(2)-CS(1) interval was increased up to 13 ms. When facilitation was present with a CS(single)-TS interval of 10 ms, a small but non-significant extra-facilitation occurred at ISIs between CS(2) and CS(1) of 6-15 ms. CONCLUSIONS: Two subthreshold conditioning stimuli facilitate inhibition that lacks the rapid periodicity typical of I-wave interaction. The data would be compatible with a model in which synaptic inputs converge on a common inhibitory interneurone.

Adult↗

Parietal magnetic stimulation delays visuomotor mental rotation at increased processing demands.

Visuomotor rotation (VMR) is a variant of the classic mental rotation paradigm. Subjects perform a center-out arm reaching movement, with the instruction to point clockwise or anticlockwise away from the direction of a reaction signal by a prespecified amount. Like classic mental rotation (MR) tasks, there is a linear relationship between reaction time (RT) and required angle of rotation (angular disparity). Although functional imaging studies have consistently demonstrated parietal activations centered around the intraparietal sulcus during MR tasks, the involvement of parietal cortex in VMR has not been investigated. The aim of the present experiments was to test in human subjects whether VMR also involves activity in parietal areas. We used short trains of transcranial magnetic stimulation (TMS) to produce a temporary "virtual lesion" of the posterior parietal cortex (PPC) around the intraparietal sulcus during the reaction period of a VMR task. Four pulses of 20-Hz rTMS were applied to the left PPC, right PPC, or vertex (control condition) 100 ms after the presentation of an instruction cue. Reaction times (RTs) were evenly prolonged by right or left parietal TMS compared with vertex stimulation, but only for large angles of rotation, and without affecting the spatial accuracy of the final response. A control experiment showed that parietal rTMS did not impair visual perception or the ability to judge the size of visual angles. The data thus provide evidence for bilateral involvement of the PPC in VMR that increases with processing demands.

Adult↗

Functional MRI of cortical activations induced by transcranial magnetic stimulation (TMS).

The effects of repetitive transcranial magnetic stimulation (rTMS) on human brain activity and associated hemodynamics were investigated by blood-oxygenation-level-dependent (BOLD) MRI using echo-planar imaging at 2.0 T. Apart from bilateral activation of the auditory cortex by the audible rTMS discharges (23 bursts, 1 s duration, 10 Hz, 10-20 s interstimulus intervals), BOLD responses were restricted to cortical representations of actual finger movements performed either voluntarily or evoked by suprathreshold rTMS of the motor cortex. Neither subthreshold rTMS of the motor cortex nor suprathreshold rTMS of the lateral premotor cortex induced a detectable BOLD response. These findings suggest that neuronal depolarization as induced by rTMS modulates the spiking output of a brain area but does not automatically alter cerebral blood flow and oxygenation. The observation of BOLD MRI activations probably reflects the afferent intracortical processing of real movements.

Adult↗

Age-related decrease in paired-pulse intracortical inhibition in the human primary motor cortex.

Using biphasic magnetic stimuli, paired-pulse transcranial magnetic stimulation (TMS) at short interstimulus intervals (ISIs) was employed to investigate age-related changes in the balance between intracortical inhibition and facilitation. In 26 right-handed healthy individuals, motor evoked potentials were recorded from the relaxed right first dorsal interosseus muscle after paired-pulse TMS of the left primary motor hand area. The magnitude of intracortical paired-pulse inhibition at ISIs of 1-5 ms was markedly reduced in elderly individuals, whereas no age effect was observed for intracortical paired-pulse facilitation at ISIs of 11-15 ms. This finding demonstrates that normal aging is associated with a relative decrease in the excitability of intracortical inhibitory circuits. In conclusion, paired-pulse TMS provides a non-invasive means of studying age-related functional changes in the motor cortex.

Adult↗

Decreased corticospinal excitability after subthreshold 1 Hz rTMS over lateral premotor cortex.

OBJECTIVE: To study whether trains of subthreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) over premotor, prefrontal, or parietal cortex can produce changes in excitability of motor cortex that outlast the application of the train. BACKGROUND: Prolonged 1 Hz rTMS over the motor cortex can suppress the amplitude of motor-evoked potentials (MEP) for several minutes after the end of the train. Because TMS can produce effects not only at the site of stimulation but also at distant sites to which it projects, the authors asked whether prolonged stimulation of sites distant but connected to motor cortex can also lead to lasting changes in MEP. METHODS: Eight subjects received 1500 magnetic stimuli given at 1 Hz over the left lateral frontal cortex, the left lateral premotor cortex, the hand area of the left motor cortex, and the left anterior parietal cortex on four separate days. Stimulus intensity was set at 90% active motor threshold. Corticospinal excitability was probed by measuring the amplitude of MEP evoked in the right first dorsal interosseous muscle by single suprathreshold stimuli over the left motor hand area before, during, and after the conditioning trains. RESULTS: rTMS over the left premotor cortex suppressed the amplitude of MEP in the right first dorsal interosseous muscle. The effect was maximized (approximately 50% suppression) after 900 pulses and outlasted the full train of 1500 stimuli for at least 15 minutes. Conditioning rTMS over the other sites did not modify the size of MEP. A control experiment showed that left premotor cortex conditioning had no effect on MEP evoked in the left first dorsal interosseous muscle. CONCLUSIONS: Subthreshold 1 Hz rTMS of the left premotor cortex induces a short-lasting inhibition of corticospinal excitability in the hand area of the ipsilateral motor cortex. This may provide a model for studying the functional interaction between premotor and motor cortex in healthy subjects and patients with movement disorders.

Adult↗

Continuous transcranial magnetic stimulation during positron emission tomography: a suitable tool for imaging regional excitability of the human cortex.

In six healthy volunteers, H(2)(15)O positron emission tomography (PET) was employed to evaluate rate-dependent functional activation of the left primary sensorimotor hand area (SM1(HAND)) during subthreshold repetitive transcranial magnetic stimulation (rTMS). Using an eight-shaped coil, continuous trains of rTMS were delivered during nine 50-s H(2)(15)O PET scans. Nine different stimulation frequencies were used, ranging from 1 to 5 Hz. Stimulus intensity was set at 10% below active motor threshold. During three additional PET scans, an ineffective rTMS was applied via another eight-shaped coil, which was held 10 cm above the vertex. Statistical parametric mapping was employed to assess relative differences in normalized regional cerebral blood flow (rCBF) across conditions. Compared with ineffective rTMS, subthreshold rTMS increased normalized rCBF in the stimulated SM1(HAND). Moreover, the increase in rCBF in the left SM1(HAND) showed a linear positive relationship with the rate of rTMS, indicating a rate-dependent functional activation of the stimulated SM1(HAND). These data demonstrate that, by varying the variables of rTMS across scans, continuous rTMS during H(2)(15)O PET provides a noninvasive tool to study the regional excitability profile of a distinct cortical area.

Adult↗

[New insights into brain function by combination of transcranial magnetic stimulation and functional brain mapping].

The present paper aims to summarize potential applications of transcranial magnetic stimulation (TMS) combined with functional brain imaging. Transcranial magnetic stimulation is a well-established noninvasive tool for stimulating circumscribed areas of the human cortex. Functional imaging techniques such as positron emission tomography, functional magnetic resonance imaging, and electroencephalographic mapping enable assessment of TMS-related functional brain activation. A combination of TMS and functional imaging can be useful in three principal ways. (1) Brain imaging before TMS is helpful in defining the accurate coil position over a distinct cortical area which is targeted by TMS. Since TMS can be used to interfere with regional cortical function during a given task, the effects of focal TMS on task performance can help to clarify the task-specific functional contribution of a given cortical area which has previously shown task-related activation in a functional imaging study. (2) Imaging the brain during TMS is a promising approach for assessing cortical excitability and intracerebral functional connectivity. (3) By evaluating lasting effects of TMS, brain imaging after TMS can be employed to study the plasticity of the human cortex. Moreover, this approach will help to advance our understanding of therapeutical effects related to TMS.

Brain↗

Brain correlates of fast and slow handwriting in humans: a PET-performance correlation analysis.

The present study examined the cerebral control of velocity during handwriting. We employed H215O positron emission tomography (PET) to measure the regional cerebral blood flow (rCBF) in 10 healthy subjects. Participants were required to write the German verb 'bellen' ('to bark') either at their normal speed (i.e. fast open-loop handwriting) or to write at approximately half of their normal speed without visual feedback. The second task required a continuous modification of the motor output according to the kinaesthetic feedback from the hand (i.e. slow closed-loop handwriting). Pencil movements were recorded during PET scanning and analysed off-line using a stroke-based analysing program. The mean number of inversions in velocity (NIV) per stroke was used to quantify the mode of motor control during each PET scan. A NIV of 1 indicates fast open-loop processing, whereas an increase in NIV reflects a shift towards slow closed-loop processing of handwriting. Foci in the left primary sensorimotor cortex, the right lateral premotor cortex, the left anterior parietal cortex, the left anterior putamen, the left rostral supplementary motor area and the right precuneus showed a graded increase in functional activation with the mean NIV per stroke, suggesting that this set of brain regions is particularly involved in the processing of slow closed-loop writing movements. No area showed a negative relationship between rCBF and the mean NIV per stroke, suggesting that fast open-loop handwriting is achieved by an optimized cooperation of the manual sensorimotor network rather than by a selective activation of a distinct network component.

Adult↗

Subthreshold 5-Hz repetitive transcranial magnetic stimulation of the human primary motor cortex reduces intracortical paired-pulse inhibition.

Paired-pulse transcranial magnetic stimulation (TMS) at short interstimulus intervals was employed to investigate short-term effects of 5-Hz repetitive TMS (rTMS) over the primary motor hand area (M1(HAND)) on intracortical excitability. In ten healthy individuals, 1250 pulses of 5-Hz rTMS were applied at 90% of motor resting threshold over the left M1(HAND). Ten minutes after 5-Hz rTMS, paired-pulse inhibition was significantly reduced, whereas paired-pulse facilitation was not modified. Sham-rTMS had no lasting effect on intracortical excitability. These findings suggest that subthreshold 5-Hz rTMS causes a short-term modulation of the excitability of intracortical circuitry in the stimulated M1(HAND). The lasting effect of subthreshold 5-Hz rTMS on intracortical inhibition provides a useful probe for studying short-term plasticity of the human M1(HAND).

Adult↗