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U Ziemann

Publications and source records attributed to U Ziemann.

At least 37 records · Page 2Linked to original sources

New graphical method to measure silent periods evoked by transcranial magnetic stimulation.

OBJECTIVES: Manual methods of measuring duration of cortical silent periods (CSP) evoked by transcranial magnetic stimulation (TMS) depend upon subjective visual estimation of onset and offset. Because of this, the measurements are susceptible to poor rater reliability. We describe a graphical method to measure silent periods with greater precision. The statistical process underlying this new method is simple and particularly suited to signal detection in serially dependent data. METHODS: TMS-evoked silent periods were recorded in 13 healthy subjects. Two investigators subjectively measured silent period duration on each subject to estimate rater reliability. Using the graphical method, the mean and 99.76% variation limits of pre-stimulus electromyogram (EMG) activity were computed. Each averaged trial was displayed and CSP onset and offset detected when post-stimulus EMG activity moved outside the 99.76% limits. RESULTS: Maximum variation in silent period duration was 21.8 ms between the two investigators' subjective measurements. Silent period duration measured with the graphical method closely approximated measurements obtained using the manual method. It was possible to automate the procedure. CONCLUSIONS: This graphical method allowed precise measurement of CSP duration, independent of subjective estimations of onset or offset points. Further studies are necessary to determine if this method can provide a framework for other physiologic measures.

Adolescent↗

Modulation of practice-dependent plasticity in human motor cortex.

Motor practice may lead to expansion of trained representations in the motor cortex, but it is unknown whether this practice-dependent plasticity can be purposefully enhanced or depressed. Evidence, mainly based on animal experiments, indicates that the activity of GABA-related cortical inhibition is important in controlling the extent to which plasticity may occur. We tested the role of GABA in modulating practice-dependent plasticity in the human motor cortex. A decrease in GABA-related cortical inhibition was achieved by ischaemic nerve block (INB) in the hand by deafferentation/deefferentation and an increase was achieved by administration of the GABA(A) receptor agonist lorazepam. In Experiment 1, healthy subjects performed motor practice (MP), consisting of repeated ballistic contractions of the biceps muscle in the absence (MP alone) or presence of INB (MP+INB). Changes in the biceps motor cortex representation were assessed by transcranial magnetic stimulation (TMS). MP+INB resulted in a dramatic increase in the size of the motor evoked potential (MEP) and in paired-pulse excitability compared with mild or no changes in the MP-alone and INB-alone conditions. In Experiment 2, this dramatic increase in biceps representation induced by MP+INB was replicated when subjects were pretreated with placebo, but this increase was prevented or even switched to a decrease when subjects were pretreated with lorazepam. These findings indicate that a decrease in GABA-related inhibition facilitates practice-dependent plasticity in the human motor cortex, whereas an increase depresses it. In Experiment 3, practice-dependent plasticity (assessed by TMS, as in the first two experiments) was also tested at the behavioural level. The dramatic increase in biceps MEP size induced by MP+INB was paralleled by an increase in peak acceleration of the fastest elbow flexion movements. Similarly, the lack of change in MEP size in the MP-alone condition was paralleled by a lack of change in peak acceleration. We propose that changes in GABA activity may be instrumented to modulate plasticity purposefully; for instance, to enhance plastic change and recovery of function after a lesion in neurological patients.

Adult↗

Analogous corticocortical inhibition and facilitation in ipsilateral and contralateral human motor cortex representations of the tongue.

How the human brain controls activation of the ipsilateral part of midline muscles is unknown. We studied corticospinal and corticocortical network excitability of both ipsilateral and contralateral motor representations of the tongue to determine whether they are under analogous or disparate inhibitory and facilitatory corticocortical control. Motor evoked potentials (MEPs) to unilateral focal transcranial magnetic stimulation (TMS) of the tongue primary motor cortex were recorded simultaneously from the ipsilateral and contralateral lingual muscles. Single-pulse TMS was used to assess motor threshold (MT) and MEP recruitment. Paired-pulse TMS was used to study intracortical inhibition (ICI) and intracortical facilitation (ICF) at various interstimulus intervals (ISIs) between the conditioning stimulus (CS) and the test stimulus (TS), and at different CS and TS intensities, respectively. Focal TMS invariably produced MEPs in both ipsilateral and contralateral lingual muscles. MT was lower and MEP recruitment was steeper when recorded from the contralateral muscle group. ICI and ICF were identical in the ipsilateral and contralateral representations, with inhibition occurring at short ISIs (2 and 3 ms) and facilitation occurring at longer ISIs (10 and 15 ms). Moreover, changing one stimulus parameter regularly produced analogous changes in MEP size bilaterally, revealing strong linear correlations between ipsilateral and contralateral ICI and ICF (P < 0.0001). These findings indicate that the ipsilateral and contralateral representations of the tongue are under analogous inhibitory and facilitatory control, possibly by a common intracortical network.

Adult↗

The relative metabolic demand of inhibition and excitation.

By using the (14C)2-deoxyglucose method, inhibition has been shown to be a metabolically active process at the level of the synapse. This is supported by recent results from magnetic resonance spectroscopy that related the changes in neuroenergetics occurring with functional activation to neurotransmitter cycling. However, inhibitory synapses are less numerous and strategically better located than excitatory synapses, indicating that inhibition may be more efficient, and therefore less energy-consuming, than excitation. Here we test this hypothesis using event-related functional magnetic resonance imaging in volunteers whose motor cortex was inhibited during the no-go condition of a go/no-go task, as demonstrated by transcranial magnetic stimulation. Unlike excitation, inhibition evoked no measurable change in the blood-oxygenation-level-dependent signal in the motor cortex, indicating that inhibition is less metabolically demanding. Therefore, the 'activation' seen in functional imaging studies probably results from excitation rather than inhibition.

Adult↗

Reorganization of the motor cortex in a patient with congenital hemiparesis and mirror movements.

Abnormal branching of corticospinal fibers from the unaffected motor cortex is responsible for mirror movements in patients with congenital hemiparesis, but it is unknown which mechanisms enable these patients to lateralize motor activity. Using multiunit electromyographic analysis and transcranial magnetic stimulation, the authors provide evidence for nonbranched crossed and uncrossed corticospinal projections and intracortical inhibition of the mirror hand. They propose that this remarkable reorganization of the unaffected motor cortex helps these patients to reduce mirror movements.

Adult↗

Altered cortical excitability in obsessive-compulsive disorder.

OBJECTIVE: To assess cortical inhibitory and excitatory mechanisms in obsessive-compulsive disorder (OCD). BACKGROUND: Transcranial magnetic stimulation (TMS) studies have found decreased neuronal inhibition and a reduced cortical silent period in the primary motor area in Tourette's syndrome, focal dystonia, and other disorders believed to involve dysfunction of subcortical structures, including the basal ganglia. Dysfunction of the basal ganglia and linked regions also has been implicated in OCD, which has significant clinical and familial overlap with tic disorders. METHODS: We applied the TMS techniques previously used in Tourette's syndrome to a group of 16 OCD patients (seven unmedicated) and 11 age-matched healthy volunteers extensively screened for psychopathology. Measures of motor cortex excitability included resting and active motor threshold, cortical silent period duration, and intracortical inhibition and facilitation using a paired-pulse TMS technique with a subthreshold conditioning stimulus. RESULTS: Similar to recent findings in Tourette's syndrome and focal dystonia, this study reports significantly decreased intracortical inhibition (ICI) relative to the volunteers at interstimulus intervals from 2 to 5 msec. We also found decreased active and resting motor evoked potential threshold in the OCD patients, another indication of increased cortical excitability. Neither abnormality appeared medication related. The decreases in ICI and motor threshold were greatest in OCD patients with comorbid tics, but remained significant in patients without tics. CONCLUSIONS: The data suggest abnormal cortical excitability in obsessive-compulsive disorder. These findings are congruent with the hypothesis that Tourette's syndrome and obsessive-compulsive disorder (OCD) are analogous disorders with overlapping dysfunction in corticobasal circuits. Patients with tic-related OCD may have more abnormal motor cortex excitability than OCD patients without tics.

Adolescent↗

Reproducibility of intracortical inhibition and facilitation using the paired-pulse paradigm.

We have evaluated the reproducibility of intracortical inhibition (ICI) and facilitation (ICF) studied with paired-pulse focal transcranial magnetic stimulation. Three investigators studied the same subjects (n = 4) in three different sessions. A high variability was shown across subjects [coefficient of variation, (cv) 67.3% for ICI and 21.2% for ICF]. Intersession variability was up to 37.1% for ICI and 22.7% for ICF. Interinvestigator variability was 17.3% for ICI and negligible for ICF. Our results may have implications for planning future studies.

Adult↗

BOLD-f MRI response to single-pulse transcranial magnetic stimulation (TMS).

Five healthy volunteers were studied using interleaved transcranial magnetic stimulation/functional magnetic resonance imaging (TMS/fMRI) and an averaged single trial (AST) protocol. Blood oxygenation level-dependent (BOLD)-fMRI response to single TMS pulses over the motor cortex was detectable in both the ipsilateral motor cortex under the TMS coil and the contralateral motor cortex, as well as bilaterally in the auditory cortex. The associated BOLD signal increase showed the typical fMRI hemodynamic response time course. The brain's response to a single TMS pulse over the motor cortex at 120% of the level required to induce thumb movement (1.0%-1.5% signal increase) was comparable in both level and duration to the auditory cortex response to the sound accompanying the TMS pulse (1.5% -2.0% signal increase).

Adult↗

Exploration of motor cortex excitability in a diabetic patient with hemiballism-hemichorea.

Hemiballism-hemichorea in older patients with hyperglycemia, associated with high signal intensity in the contralateral striatum on T1-weighted magnetic resonance scans, is now an accepted clinical entity. We present an additional patient with this disorder. Using transcranial magnetic stimulation, we show that intracortical inhibition in the motor cortex contralateral to hemiballism-hemichorea is increased. This finding is discussed in the context of current models of basal ganglia-thalamo-cortical connectivity.

Aged↗

Effects of low-frequency transcranial magnetic stimulation on motor excitability and basic motor behavior.

OBJECTIVE: To explore effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) on motor excitability and basic motor behavior in humans. DESIGN AND METHODS: Seven normal volunteers underwent 1 Hz rTMS of the hand representation of the right M1 for 15 min at an intensity of 115% of the individual resting motor threshold. The effects of rTMS on motor excitability were assessed by monitoring changes in individual resting motor threshold and input-output curves of motor evoked potentials (MEPs) in the flexor pollicis brevis, first dorsal interosseus, abductor digiti minimi and biceps brachii muscles. Changes in basic motor behavior were studied by measuring maximal and mean peak force and peak accelerations of thumb flexions and abductions of the fifth finger before and after rTMS. RESULTS: rTMS produced a significant increase in resting motor threshold and a significant suppression of MEP input-output curves that persisted for 30 min. The suppressing effect was restricted to the hand motor representation which was the prime target of the stimulation procedure, and there were no significant effects on the biceps representation. Peak force and peak acceleration were not affected while the motor representations of muscles involved in the behavioral measurements were significantly suppressed by rTMS. CONCLUSIONS: Low-frequency rTMS of M1 transiently depresses motor excitability but this does not affect basic motor behavior. This is relevant for the therapeutic use of low-frequency rTMS in disorders with abnormal cortical excitability.

Adult↗

I-waves in motor cortex.

I-waves refer to high-frequency (approximately 600 Hz) repetitive discharge of corticospinal fibers produced by single-pulse stimulation of the motor cortex. First detected in animal preparations, this multiple discharge can also be recorded in humans with epidural electrodes over the spinal cord, and with recently developed noninvasive paired-pulse transcranial magnetic stimulation protocols. The exact nature of the generation of I-waves is still unclear, but there is convincing evidence that they originate in the motor cortex, mainly through activation of corticocortical projections onto corticospinal neurons. The ability to measure I-waves in human motor cortex allows one to test the integrity and excitability of the underlying corticocortical circuits in health and disease.

Humans↗

Altered seizure susceptibility after high-frequency transcranial magnetic stimulation in rats.

The long-term effect of repetitive transcranial magnetic stimulation (rTMS) on the susceptibility of amygdala kindling was studied. Two weeks after a single high-frequency rTMS train (120 A/micros, 20 Hz for 3 s), the rats had a 55% higher threshold for induction of epileptic afterdischarges compared with sham-treated or control rats. However, subsequent kindling revealed no difference between rTMS-treated and control rats. Our data suggest that a single rTMS train has long-term effects on the neuronal excitability. These effects may be anticonvulsant and therefore support the safety of rTMS in clinical use.

Amygdala↗

Dissociation of the pathways mediating ipsilateral and contralateral motor-evoked potentials in human hand and arm muscles.

1. Growing evidence points toward involvement of the human motor cortex in the control of the ipsilateral hand. We used focal transcranial magnetic stimulation (TMS) to examine the pathways of these ipsilateral motor effects. 2. Ipsilateral motor-evoked potentials (MEPs) were obtained in hand and arm muscles of all 10 healthy adult subjects tested. They occurred in the finger and wrist extensors and the biceps, but no response or inhibitory responses were observed in the opponens pollicis, finger and wrist flexors and the triceps. 3. The production of ipsilateral MEPs required contraction of the target muscle. The threshold TMS intensity for ipsilateral MEPs was on average 1.8 times higher, and the onset was 5.7 ms later (in the wrist extensor muscles) compared with size-matched contralateral MEPs. 4. The corticofugal pathways of ipsilateral and contralateral MEPs could be dissociated through differences in cortical map location and preferred stimulating current direction. 5. Both ipsi- and contralateral MEPs in the wrist extensors increased with lateral head rotation toward, and decreased with head rotation away from, the side of the TMS, suggesting a privileged input of the asymmetrical tonic neck reflex to the pathway of the ipsilateral MEP. 6. Large ipsilateral MEPs were obtained in a patient with complete agenesis of the corpus callosum. 7. The dissociation of the pathways for ipsilateral and contralateral MEPs indicates that corticofugal motor fibres other than the fast-conducting crossed corticomotoneuronal system can be activated by TMS. Our data suggest an ipsilateral oligosynaptic pathway, such as a corticoreticulospinal or a corticopropriospinal projection as the route for the ipsilateral MEP. Other pathways, such as branching of corticomotoneuronal axons, a transcallosal projection or a slow-conducting monosynaptic ipsilateral pathway are very unlikely or can be excluded.

Adolescent↗

Changes in 5-HT1A and NMDA binding sites by a single rapid transcranial magnetic stimulation procedure in rats.

The effects of a single rapid-rate transcranial magnetic stimulation (rTMS) exposure on neurotransmitter binding sites in the rat brain 24 h after the stimulation were examined. Quantification by in vitro-autoradiography showed no differences for 3H-paroxetine binding (5-HT uptake sites) between rTMS-treated, sham and control animals. In contrast, the number of 5-HT1A binding sites (labeled with 3H-8-OH-DPAT) were selectively increased in the rTMS-group with significantly higher BMAX values in the frontal cortex, the cingulate cortex, and the anterior olfactory nucleus. A non-specific increase in NMDA binding sites (labeled with 125I-MK-801) in rTMS and sham animals was observed in the hippocampal formation. A selective increase of these binding sites after rTMS was detected in the ventromedial hypothalamus, the basolateral amygdala and layers 5-6 of the parietal cortex. These findings imply that a single rTMS exposure can result in persistent effects on NMDA and 5-HT1A binding sites even 24 h after stimulation and therefore may be of relevance with respect to the therapeutic action of rTMS reported from clinical studies.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Complete suppression of voluntary motor drive during the silent period after transcranial magnetic stimulation.

To evaluate changes in the motor system during the silent period (SP) induced by transcranial magnetic stimulation (TMS) of the motor cortex, we investigated motor thresholds as parameters of the excitability of the cortico-muscular pathway after a suprathreshold conditioning stimulus in the abductor digiti minimi muscle (ADM) of normal humans. Since the unconditioned motor threshold was lower during voluntary tonic contraction than at rest (31.9+/-5.4% vs. 45.6+/-7.5%), it is suggested that the difference between active and resting motor threshold indicates the magnitude of the voluntary drive on the cortico-muscular pathway. Therefore, we compared conditioned resting and active motor threshold (cRMT and cAMT) during the SP. cRMT showed an intensity-dependent period of elevation of more than 200 ms in duration and approximately 17% of the maximum stimulator output above the unconditioned threshold, due to decreased excitability of the cortico-muscular pathway after the conditioning stimulus. Some 3040 ms after the conditioning stimulus, cAMT approximated cRMT, indicating complete suppression of the voluntary motor drive. This suppression did not start directly after the conditioning stimulus since cAMT was still significantly lower than the cRMT within the first 30-40 ms. Threshold elevation was significantly longer than the SP (220+/-41 vs. 151+/-28 ms). Recovery of the voluntary motor drive started late in the SP and was nearly complete at the end of the SP, although thresholds were still significantly elevated. We conclude that the SP is largely due to a suppression of voluntary motor drive, while the threshold elevation is a different inhibitory phenomenon that is of less importance for the generation of the SP, at least in its late part. It is argued that the pathway of fast cortico-spinal fibers activated by TMS is partially different from the pathway involved in the maintenance of tonic voluntary muscle activation.

Adult↗

Two periods of processing in the (circum)striate visual cortex as revealed by transcranial magnetic stimulation.

To determine the timing of visual processing in the (circum)striate visual cortex, we examined the effect of single pulse transcranial magnetic stimulation over the occipital pole of healthy subjects who were engaged in a forced-choice visual letter identification task. Single letters, subtending a visual angle of 0.35 degrees, were foveally presented for 10 ms and were immediately followed by a mask. We investigated 30 different delays (d), defined as the time between the onset of the visual stimulus and the onset of the magnetic stimulus, from d = -100 ms to d = +190 ms, and 4 different midsagittal coil positions (x), defined as the distance between the lower edge of the coil and the upper edge of the inion, from x = 1 cm to x = 7 cm. Three out of four subjects showed three distinct delay intervals (dips) at which application of TMS resulted in an impairment of the task. The first dip was centred around d = -50 ms and occurred independently of the coil position; the second dip was centred around d = 0 ms and was elicitable only with the two lowest coil positions; the third dip was centred around d = 100 ms and was also elicitable only with the lower coil positions. In the fourth subject, only the first and the third dip were found. We conclude that there are two distinct periods when the activity in the (circum)striate visual cortex is necessary for the identification of visually presented letters.

Electromagnetic Phenomena↗