Biomedical subjects

Ulf Ziemann

Publications and source records attributed to Ulf Ziemann.

10 recordsLinked to original sources

PubMed2003

Methylphenidate facilitates and disinhibits the motor cortex in intact humans.

Animal experiments show that motor recovery after focal brain injury is accelerated by the indirect norepinephrine agonist methylphenidate (MPH). The underlying mechanisms are unknown, but an MPH-induced increase in cortical excitability has been advocated. Here, we tested the acute effects of a single oral dose of 40 mg MPH (Ritalin) on motor cortical excitability in eight healthy subjects using focal transcranial magnetic stimulation. MPH increased the slope of the motor evoked potentials (MEP) intensity curve in a hand muscle, reduced short-interval intracortical inhibition, and increased I-wave facilitation. MEP threshold, cortical silent period and measures of spinal and neuromuscular excitability remained unaffected. Findings support the idea that MPH promotes accelerated motor recovery after lesion through facilitation and disinhibition.

Adult↗

PubMed2002

Short-interval paired-pulse inhibition and facilitation of human motor cortex: the dimension of stimulus intensity.

Paired transcranial magnetic stimulation has greatly advanced our understanding of the mechanisms which control excitability in human motor cortex. While it is clear that paired-pulse excitability depends on the exact interstimulus interval (ISI) between the first (S1) and second stimulus (S2), relatively little is known about the effects of the intensities of S1 and S2, and the effects of manipulating neurotransmission through the GABA(A) receptor. When recording the motor evoked potential (MEP) from the resting abductor digiti minimi (ADM) muscle, using a fixed ISI of 1.5 ms, and expressing the interaction between S1 and S2 as MEP(S1+S2)/(MEP(S1) + MEP(S2)), then a systematic variation of the intensities of S1 and S2 revealed short-interval intracortical facilitation (SICF) if S1 and S2 were approximately equal to MEP threshold (RMT), or if S1 > RMT and S2 < RMT. In contrast, short-interval intracortical inhibition (SICI) occurred if S1 < RMT and S2 > RMT. Contraction of the ADM left SICI unchanged but reduced SICF. The GABA(A) receptor agonist diazepam increased SICI and reduced SICF in the resting ADM while diazepam had no effect during ADM contraction. Surface EMG and single motor unit recordings revealed that during ADM contraction SICI onset was at the I3-wave latency of S2, whereas SICF typically "jumped up" by one I-wave and started with the I2-wave latency of S2. Findings suggest that SICI is mediated through a low-threshold GABA(A) receptor-dependent inhibitory pathway and summation of IPSP from S1 and EPSP from S2 at the corticospinal neurone. In contrast, SICF originates through non-synaptic facilitation at the initial axon segment of interneurones along a high-threshold excitatory pathway.

Adult↗

PubMed2002

Transitions between dynamical states of differing stability in the human brain.

What mechanisms underlie the flexible formation, adaptation, synchronization, and dissolution of large-scale neural assemblies from the 10(10) densely interconnected, continuously active neurons of the human brain? Nonlinear dynamics provides a unifying perspective on self-organization. It shows that the emergence of patterns in open, nonequilibrium systems is governed by their stability in response to small disturbances and predicts macroscopic transitions between patterns of differing stability. Here, we directly demonstrate that such transitions can be elicited in the human brain by interference at the neural level. As a probe, we used a classic motor coordination paradigm exhibiting well described movement states of differing stability. Functional neuroimaging identified premotor (PMA) and supplementary motor (SMA) cortices as having neural activity linked to the degree of behavioral instability. These regions then were transiently disturbed with graded transcranial magnetic stimulation, which caused sustained and macroscopic behavioral transitions from the less stable out-of-phase to the stable in-phase movement, whereas the stable pattern could not be affected. Moreover, the strength of the disturbance needed (a measure of neural stability) was linked to the degree of behavioral stability, demonstrating the applicability of nonlinear system theory as a powerful predictor of the dynamical repertoire of the human brain.

Adult↗

PubMed2002

Stimulation-induced within-representation and across-representation plasticity in human motor cortex.

The human motor cortex contains a dynamic and distributed network of motor representations. Formation, maintenance, and modification of these representations is an activity-driven process. Repeated stimulation of one representation results in increased motor output from this representation, a process referred to as "within-representation plasticity." We showed previously that within-representation plasticity of the upper arm representation occurs when repetitive transcranial magnetic stimulation (rTMS) is delivered to that representation during transient ischemic nerve block (INB) of the contralateral hand. INB reduces inhibition in the motor cortex and thus lowers the threshold for stimulation-induced plasticity. Here we studied the effects of rTMS delivered to nearby body part representations on the motor output from the upper arm representation. Six healthy subjects underwent INB-alone (control), or INB plus 30 min of focal 0.1 Hz rTMS of either the face, hand, arm, leg, or overlap arm/hand representations in motor cortex. INB-alone and rTMS of the leg representation resulted in only a short-lasting (< 20 min) increase in motor output from the arm representation, as measured by motor evoked potentials in the biceps. rTMS of arm and arm/hand representations induced a prolonged (> 60 min) within-representation increase. In contrast, rTMS of face or hand representations canceled the short-lasting increase and even led to a long-lasting decrease of motor output from the arm representation. Therefore, rTMS of the experimentally disinhibited motor cortex induces within-representation increase, and across-representation decrease of motor cortical output. This bidirectional plasticity might be used for purposeful modulation of human cortical function.

Adult↗

PubMed2002

Complex modulation of human motor cortex excitability by the specific serotonin re-uptake inhibitor sertraline.

Monoamines are powerful modulators of cortical function. Serotonin has complex excitatory and inhibitory effects on animal cortex. Here, the effects of a single oral dose (100mg) of the selective serotonin re-uptake inhibitor sertraline on human motor cortex excitability were investigated in healthy subjects. Transcranial magnetic stimulation was used to test motor threshold, motor evoked potential intensity curve, cortical silent period, paired-pulse inhibition and facilitation and I-wave facilitation. Sertraline resulted in a steeper intensity curve and in depressed paired-pulse facilitation (PPF). All other measures and spinal and neuromuscular excitability remained unaffected. The steeper intensity curve points to an increased excitability of the cortico-spinal neurone, while the depressed PPF suggests an enhanced control of the cortico-spinal neurone by inhibitory interneurones. These features may improve the signal-to-noise ratio of output cells in human motor cortex.

Adult↗

PubMed2002

Early consolidation in human primary motor cortex.

Behavioural studies indicate that a newly acquired motor skill is rapidly consolidated from an initially unstable state to a more stable state, whereas neuroimaging studies demonstrate that the brain engages new regions for performance of the task as a result of this consolidation. However, it is not known where a new skill is retained and processed before it is firmly consolidated. Some early aspects of motor skill acquisition involve the primary motor cortex (M1), but the nature of that involvement is unclear. We tested the possibility that the human M1 is essential to early motor consolidation. We monitored changes in elementary motor behaviour while subjects practised fast finger movements that rapidly improved in movement acceleration and muscle force generation. Here we show that low-frequency, repetitive transcranial magnetic stimulation of M1 but not other brain areas specifically disrupted the retention of the behavioural improvement, but did not affect basal motor behaviour, task performance, motor learning by subsequent practice, or recall of the newly acquired motor skill. These findings indicate that the human M1 is specifically engaged during the early stage of motor consolidation.

Adult↗

PubMed2002

Improving hand function in chronic stroke.

BACKGROUND: Recovery of function following stroke plateaus in about 1 year, typically leaving upper arm function better than that in the hand. Since there is competition among body parts for territory in the sensorimotor cortex, even limited activity of the upper arm might prevent the hand from gaining more control, particularly when the territory is reduced in size because of the stroke. Deafferentation of a body part in a healthy brain enhances cortical representations of adjacent body parts, and this effect is markedly increased by voluntary activity of the adjacent part. OBJECTIVE: To explore whether deafferentation of the upper arm, produced by a new technique of regional anesthesia during hand motor practice, helps recovery of hand function in patients with long-term stable weakness of their hand following stroke. METHODS AND RESULTS: Deafferentation, produced by a new technique of regional anesthesia of the upper arm during hand motor practice, dramatically improved hand motor function including some activities of daily living. The improvement was associated with an increase in transcranial magnetic stimulation-evoked motor output to the practice hand muscles. CONCLUSION: This is a novel therapeutic strategy that may help improve hand function in patients with long-term weakness after stroke.

Afferent Pathways↗

PubMed2002

Myoclonus-dystonia syndrome: epsilon-sarcoglycan mutations and phenotype.

Mutations in the gene for epsilon-sarcoglycan (SGCE) have been found to cause myoclonus-dystonia syndrome. We now report clinical and genetic findings in nine additional European families with myoclonus-dystonia syndrome. The clinical presentation in 24 affecteds was homogeneous with myoclonus predominantly of neck and upper limbs in 23 of them and dystonia, presenting as cervical dystonia and/or writer's cramp, in 13 cases. Six novel and one previously known heterozygous SGCE mutations were identified. SGCE deficiency seems to be the common pathogenetic mechanism in myoclonus-dystonia syndrome.

Adolescent↗

PubMed2002

Rapid modulation of GABA in sensorimotor cortex induced by acute deafferentation.

Recovery of function after acute injury to the central nervous system may be controlled by the availability of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the cerebral cortex. Acute lesions as well as manipulation of sensory inputs can lead to rapid reorganization of the cerebral cortex, occurring within minutes to hours. Reduction of cortical inhibitory tone through a decrease in the availability of GABA has been suggested as a possible mechanism; however, the degree and temporal course of the changes in brain GABA are not known. A novel method using two-dimensional J-resolved magnetic resonance spectroscopy showed that GABA levels in the human sensorimotor cortex are quickly reduced within minutes of deafferentation. This finding strongly supports the view that the release of latent corticocortical projections from tonic inhibition through decreased GABA availability is a mechanism of rapid cortical plasticity. Reduction of brain GABA can play a pivotal role in regulating the extent of rapid cortical reorganization after lesions or changes in sensory input.

Adult↗

PubMed2002

Dual modulating effects of amphetamine on neuronal excitability and stimulation-induced plasticity in human motor cortex.

OBJECTIVES: The objective of the present study is to test the modulating effects of dextro-amphetamine (d-AMP) on excitability and stimulation-induced plasticity in human motor cortex. METHODS: Transcranial magnetic stimulation (TMS) was used to measure motor threshold, motor evoked potential (MEP) size and paired-pulse intracortical facilitation (ICF) in the biceps muscle of 7 healthy subjects before and after two different experimental manipulations: temporary forearm ischemic nerve block (INB) alone, or INB plus 0.1 Hz repetitive TMS (INB+rTMS) of the motor cortex contralateral to INB. Both manipulations were run after treatment with 10mg of d-AMP or placebo (PBO). RESULTS: In the PBO experiments, INB alone had no significant effect on MEP size or ICF, while INB+rTMS produced long-lasting (>60 min) increases. Compared with PBO, d-AMP led to a short-lasting ( approximately 10 min) increase in MEP size in the INB alone experiment, but suppressed the long-lasting increases of MEP size and ICF in the INB+rTMS experiment. CONCLUSIONS: The present findings suggest that d-AMP increases neuronal excitability but suppresses long-lasting stimulation-induced plasticity in human motor cortex. These dual effects may be relevant when using d-AMP to modulate human cortex function.

Adult↗