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Biomedical subjects

Michael A Nitsche

Publications and source records attributed to Michael A Nitsche.

At least 37 records · Page 2Linked to original sources

Catecholaminergic consolidation of motor cortical neuroplasticity in humans.

Amphetamine, a catecholaminergic re-uptake-blocker, is able to improve neuroplastic mechanisms in humans. However, so far not much is known about the underlying physiological mechanisms. Here, we study the impact of amphetamine on NMDA receptor-dependent long-lasting excitability modifications in the human motor cortex elicited by weak transcranial direct current stimulation (tDCS). Amphetamine significantly enhanced and prolonged increases in anodal, tDCS-induced, long-lasting excitability. Under amphetamine premedication, anodal tDCS resulted in an enhancement of excitability which lasted until the morning after tDCS, compared to approximately 1 h in the placebo condition. Prolongation of the excitability enhancement was most pronounced for long-term effects; the duration of short-term excitability enhancement was only slightly increased. Since the additional application of the NMDA receptor antagonist dextromethorphane blocked any enhancement of tDCS-driven excitability under amphetamine, we conclude that amphetamine consolidates the tDCS-induced neuroplastic effects, but does not initiate them. The fact that propanolol, a beta-adrenergic antagonist, diminished the duration of the tDCS-generated after-effects suggests that adrenergic receptors play a certain role in the consolidation of NMDA receptor-dependent motor cortical excitability modifications in humans. This result may enable researchers to optimize neuroplastic processes in the human brain on the rational basis of purpose-designed pharmacological interventions.

Adult↗

Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex.

Recent experimental work in animals has emphasized the importance of homeostatic plasticity as a means of stabilizing the properties of neuronal circuits. Here, we report a phenomenon that indicates a homeostatic pattern of cortical plasticity in healthy human subjects. The experiments combined two techniques that can produce long-term effects on the excitability of corticospinal output neurons: transcranial direct current stimulation (TDCS) and repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex. "Facilitatory preconditioning" with anodal TDCS caused a subsequent period of 1 Hz rTMS to reduce corticospinal excitability to below baseline levels for >20 min. Conversely, "inhibitory preconditioning" with cathodal TDCS resulted in 1 Hz rTMS increasing corticospinal excitability for at least 20 min. No changes in excitability occurred when 1 Hz rTMS was preceded by sham TDCS. Thus, changing the initial state of the motor cortex by a period of DC polarization reversed the conditioning effects of 1 Hz rTMS. These preconditioning effects of TDCS suggest the existence of a homeostatic mechanism in the human motor cortex that stabilizes corticospinal excitability within a physiologically useful range.

Adult↗

No correlation between moving phosphene and motor thresholds: a transcranial magnetic stimulation study.

The aim of this study was to investigate the temporal stability of moving phosphenes and to assess whether moving phosphene thresholds (PTs) correlate with motor thresholds (MTs). Small moving sensations, so-called moving phosphenes, are perceived when V5, an area important for visual motion analysis, is stimulated by transcranial magnetic stimulation (TMS). However, it is still a matter of debate if V5 phosphenes are stable sensations across measurements and if they are a reasonable index of the cortical excitability of V5. Currently, MT is more commonly used as an index of global cortical excitability. However, previous studies have indicated that stationary PTs are suitable alternatives when the primary visual cortex is stimulated by TMS. Using paired-pulse TMS, stationary and moving PTs and applying single pulse TMS, MTs were measured in 11 subjects. PTs were retested in nine subjects 5-7 days later. Stationary and moving PTs were stable within subjects across the two sessions and showed a high inter-correlation. Conversely, PTs and MTs did not correlate. Our results are in agreement with previous studies showing that excitatory measurements of one specific cortex cannot be generalized to the excitability of the whole cortex. Thus, we propose specific measures for cortices of interest: PT for visual experiments and MT for motor experiments.

Adult↗

Facilitation of probabilistic classification learning by transcranial direct current stimulation of the prefrontal cortex in the human.

The aim of our study was to test if the electrical stimulation of the prefrontal cortex (PFC) could modify probabilistic classification learning (PCL). Transcranial direct current stimulation (tDCS) was administered to the left prefrontal and to the primary visual cortex of 22 healthy subjects while they performed a PCL task. In this task subjects learned which of two outcomes would occur on each trial after presentation of a particular combination of cues. Ten minutes of anodal, but not cathodal, stimulation improved implicit learning only when the left PFC was stimulated. Our results show that implicit PLC can be modified by weak anodal tDCS, which probably increases neural excitability, as has been shown in the motor and visual cortices previously. Our results suggest that further studies on the facilitation of learning and memory processes by tDCS are warranted.

Adult↗

Effect of transcranial DC sensorimotor cortex stimulation on somatosensory evoked potentials in humans.

OBJECTIVE: To study the after-effect of transcranial direct current stimulation (tDCS) over the sensorimotor cortex on the size of somatosensory evoked potentials (SEPs) in humans. METHODS: SEPs were elicited by electrical stimulation of right or left median nerve at the wrist before and after anodal or cathodal tDCS in 8 healthy subjects. tDCS was applied for 10 min to the left motor cortex at a current strength of 1 mA. RESULTS: Amplitudes of P25/N33, N33/P40 (parietal components) and P22/N30 (frontal component) following right median nerve stimulation were significantly increased for at least 60 min after the end of anodal tDCS, whereas P14/N20, N20/P25 (parietal components) and N18/P22 (frontal component) were unaffected. There was no effect on SEPs evoked by left median nerve stimulation. Cathodal tDCS had no effect on SEPs evoked from stimulation of either arm. CONCLUSIONS: Anodal tDCS over the sensorimotor cortex can induce a long-lasting increase in the size of ipsilateral cortical components of SEPs. SIGNIFICANCE: tDCS can modulate cortical somatosensory processing in humans and might be a useful tool to induce plasticity in cortical sensory processing.

Adult↗

Consolidation of human motor cortical neuroplasticity by D-cycloserine.

D-Cycloserine (CYC), a partial N-methyl-D-aspartate (NMDA) agonist, has been shown to improve cognitive functions in humans. However, the neurophysiological basis of this effect is unclear so far. We studied the impact of this drug on long-lasting after-effects of transcranial direct current (tDCS)-generated motor cortical excitability shifts, as revealed by transcranial magnetic stimulation-elicited motor-evoked potentials. While anodal tDCS enhances motor cortical excitability, cathodal tDCS diminishes it. Both effects seem to be NMDA receptor dependent. D-CYC selectively potentiated the duration of motor cortical excitability enhancements induced by anodal tDCS. D-CYC alone did not modulate excitability. The potency of this drug to consolidate neuronal excitability enhancements, most probably by stabilizing the strengthening of NMDA receptors, which is a probable neurophysiological derivate of learning processes, makes it an interesting substance to improve cognitive functions.

Adult↗

GABAergic modulation of DC stimulation-induced motor cortex excitability shifts in humans.

Weak transcranial DC stimulation (tDCS) of the human motor cortex results in excitability shifts during and after the end of stimulation, which are most probably localized intracortically. Anodal stimulation enhances excitability, whereas cathodal stimulation reduces it. Although the after-effects of tDCS are NMDA receptor-dependent, nothing is known about the involvement of additional receptors. Here we show that pharmacological strengthening of GABAergic inhibition modulates selectively the after-effects elicited by anodal tDCS. Administration of the GABA(A) receptor agonist lorazepam resulted in a delayed, but then enhanced and prolonged anodal tDCS-induced excitability elevation. The initial absence of an excitability enhancement under lorazepam is most probably caused by a loss of the anodal tDCS-generated intracortical diminution of inhibition and enhancement of facilitation, which occurs without pharmacological intervention. The reasons for the late-occurring excitability enhancement remain unclear. Because intracortical inhibition and facilitation are not changed in this phase compared with pre-tDCS values, excitability changes originating from remote cortical or subcortical areas could be involved.

Adult↗

Transcranial direct current stimulation disrupts tactile perception.

The excitability of the cerebral cortex can be modulated by various transcranial stimulation techniques. Transcranial direct current stimulation (tDCS) offers the advantage of portable equipment and could, therefore, be used for ambulatory modulation of brain excitability. However, modulation of cortical excitability by tDCS has so far mostly been shown by indirect measures. Therefore, we examined whether tDCS has a direct behavioral/perceptional effect. We compared tactile discrimination of vibratory stimuli to the left ring finger prior to, during and after tDCS applied for 7 min at 1-mA current intensity in 13 subjects. Stimulation was pseudorandomized into cathodal, anodal and sham conditions in a within-subject design. The active electrode was placed over the corresponding somatosensory cortex at C4 according to the 10-20 EEG system and the reference electrode at the forehead above the contralateral orbita. Cathodal stimulation compared with sham induced a prolonged decrease of tactile discrimination, while anodal and sham stimulation did not. Thus, cortical processing can be modulated in a behaviorally/perceptually meaningful way by weak transcranial current stimulation applied through portable technology. This finding offers a new perspective for the treatment of conditions characterized by alterations of cortical excitability.

Adult↗

Facilitation of visuo-motor learning by transcranial direct current stimulation of the motor and extrastriate visual areas in humans.

Performance of visuo-motor tasks requires the transfer of visual data to motor performance and depends highly on visual perception and cognitive processing, mainly during the learning phase. The primary aim of this study was to determine if the human middle temporal (MT)+/V5, an extrastriate visual area that is known to mediate motion processing, and the primary motor cortex are involved in learning of visuo-motor coordination tasks. To pursue this, we increased or decreased MT+/V5, primary contralateral motor (M1) and primary visual cortex excitability by 10 min of anodal or cathodal transcranial direct current stimulation in healthy human subjects during the learning phase of a visually guided tracking task. The percentage of correct tracking movements increased significantly in the early learning phase during anodal stimulation, but only when the left V5 or M1 was stimulated. Cathodal stimulation had no significant effect. Also, stimulation of the primary visual cortex was not effective for this kind of task. Our data suggest that the areas V5 and M1 are involved in the early phase of learning of visuo-motor coordination.

Adult↗

Direct current stimulation over V5 enhances visuomotor coordination by improving motion perception in humans.

The primary aim of this study was to determine the extent to which human MT+/V5, an extrastriate visual area known to mediate motion processing, is involved in visuomotor coordination. To pursue this we increased or decreased the excitability of MT+/V5, primary motor, and primary visual cortex by the application of 7 min of anodal and cathodal transcranial direct current stimulation (tDCS) in healthy human subjects while they were performing a visuomotor tracking task involving hand movements. The percentage of correct tracking movements increased specifically during and immediately after cathodal stimulation, which decreases cortical excitability, only when V5 was stimulated. None of the other stimulation conditions affected visuomotor performance. We propose that the improvement in performance caused by cathodal tDCS of V5 is due to a focusing effect on to the complex motion perception conditions involved in this task. This hypothesis was proven by additional experiments: Testing simple and complex motion perception in dot kinetograms, we found that a diminution in excitability induced by cathodal stimulation improved the subject's perception of the direction of the coherent motion only if this was presented among random dots (complex motion perception), and worsened it if only one motion direction was presented (simple movement perception). Our data suggest that area V5 is critically involved in complex motion perception and identification processes important for visuomotor coordination. The results also raise the possibility of the usefulness of tDCS in rehabilitation strategies for neurological patients with visuomotor disorders.

Adult↗

Excitability changes induced in the human primary visual cortex by transcranial direct current stimulation: direct electrophysiological evidence.

PURPOSE: Transcranial direct current stimulation (tDCS) has been shown to modify the perception threshold of phosphenes elicited by transcranial magnetic stimulation (TMS). The current study was undertaken to examine whether tDCS, when applied over the occipital cortex, is also able to affect visual-evoked potentials (VEPs), which characterize occipital activation in response to visual stimulation, in a polarity-specific way. METHOD: For this purpose, VEPs evoked by sinusoidal luminance grating in an on/off mode were recorded before, immediately after, and 10, 20, and 30 minutes after the end of 5, 10, or 15 minutes of anodal or cathodal tDCS of the primary visual cortex. RESULTS: Significant effects were observed only when low-contrast visual stimuli were applied. Cathodal stimulation decreased, whereas anodal stimulation increased the amplitude of the N70 component. The effect of cathodal stimulation was significant immediately after and 10 minutes after the end of stimulation, if the stimulation duration was sufficiently long (i.e., 10-15 minutes). An increase of N70 amplitude by anodal stimulation was significant only 10 minutes after the end of the 15 minutes tDCS. Cathodal stimulation tended also to affect the amplitude of the P100 component; however, the effect of stimulation was inverse. The amplitude increased immediately after the end of cathodal stimulation. In contrast, anodal stimulation did not affect the P100. The latencies of the N70 and the P100 were not affected by tDCS. CONCLUSIONS: tDCS appears to be a suitable method of inducing reversible excitability changes in a polarity-specific way, not only in the motor but also in the primary visual cortex. The duration of the induced aftereffects depends not only on stimulation duration but also on stimulation polarity. Cathodal stimulation seems to be more effective, in line with previous reports on the motor cortex.

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Facilitation of implicit motor learning by weak transcranial direct current stimulation of the primary motor cortex in the human.

Transcranially applied weak direct currents are capable of modulating motor cortical excitability in the human. Anodal stimulation enhances excitability, cathodal stimulation diminishes it. Cortical excitability changes accompany motor learning. Here we show that weak direct currents are capable of improving implicit motor learning in the human. During performance of a serial reaction time task, the primary motor cortex, premotor, or prefrontal cortices were stimulated contralaterally to the performing hand. Anodal stimulation of the primary motor cortex resulted in increased performance, whereas stimulation of the remaining cortices had no effect. We conclude that the primary motor cortex is involved in the acquisition and early consolidation phase of implicit motor learning.

Analysis of Variance↗

Manipulation of phosphene thresholds by transcranial direct current stimulation in man.

Transcranial direct current stimulation (tDCS) can modulate the excitability of the human motor cortex, as revealed by the amplitude of the motor-evoked potentials (MEP). The aim of our study has been to produce localized changes of cerebral excitability of the visual cortex in the intact human by weak anodal and cathodal stimulation. For quantification of current-induced excitability changes, we measured phosphene threshold (PT) using short trains of 5-Hz transcranial magnetic stimulation (TMS) pulses in nine healthy subjects before, immediately after, 10 min, and 20 min after the end of tDCS. PTs are suggested as representative values of visual cortex excitability changes. Reduced PT was detected immediately and 10 min after the end of anodal stimulation, while cathodal stimulation resulted in an opposite effect. Our results show that tDCS elicits a transient, reversible excitability alteration of the visual cortex, thus representing a promising tool for neuroplasticity research.

Adult↗

Relationship between lamotrigine oral dose, serum level and its inhibitory effect on CNS: insights from transcranial magnetic stimulation.

The antiepileptic drug lamotrigine (LTG) is known to reduce cortical excitability evaluated by transcranial magnetic stimulation (TMS). We investigated the relationship between LTG oral dosages, serum levels and inhibitory effects on resting motor threshold (RMT), a parameter of motor system excitability assessed by TMS. In a randomized, placebo-controlled crossover study 16 male volunteers received 325 mg LTG as a single dose, as bi-hourly graded cumulative dose, or placebo. RMT and serum levels were measured before and after 2-8 h. With single dose, RMT elevation showed a poor but significant correlation to serum levels. With graded dose, serum levels as well as RMT increased dose-dependently with significant (P<0.0001) linear correlation. However, detailed comparison showed a high inter-individual variability in the relationship resembling a sigmoid correlation. Different mechanisms besides the sodium-channel blockage as the main mode of action of LTG are discussed to explain the diversity of individual dose-response relationships. Provided that the RMT elevation reflects the antiepileptic potential of LTG, TMS may be developed as a tool to monitor interindividual response of epilepsy patients to LTG treatment as well as to explore efficacy of other antiepileptic drugs with similar mode of action.

Administration, Oral↗

Modulation of moving phosphene thresholds by transcranial direct current stimulation of V1 in human.

Small moving sensations, so-called moving phosphenes are perceived, when V5, a visual area important for visual motion analysis, is stimulated by transcranial magnetic stimulation (TMS). However, it is still a matter of debate if only V5 takes part in movement perception or other visual areas are also involved in this process. In this study we tested the involvement of V1 in the perception of moving phosphenes by applying transcranial direct current stimulation (tDCS) to this area. tDCS is a non-invasive stimulation technique known to modulate cortical excitability in a polarity-specific manner. Moving and stationary phosphene thresholds (PT) were measured by TMS before, immediately after and 10, 20 and 30 min after the end of 10 min cathodal and anodal tDCS in nine healthy subjects. Reduced PTs were detected immediately and 10 min after the end of anodal tDCS while cathodal stimulation resulted in an opposite effect. Our results show that the excitability shifts induced by V1 stimulation can modulate moving phosphene perception. tDCS elicits transient, but yet reversible effects, thus presenting a promising tool for neuroplasticity research.

Adult↗

Level of action of cathodal DC polarisation induced inhibition of the human motor cortex.

OBJECTIVE: To induce prolonged motor cortical excitability reductions by transcranial direct current stimulation in the human. METHODS: Cathodal direct current stimulation was applied transcranially to the hand area of the human primary motor cortex from 5 to 9 min in separate sessions in twelve healthy subjects. Cortico-spinal excitability was tested by single pulse transcranial magnetic stimulation. Transcranial electrical stimulation and H-reflexes were used to learn about the origin of the excitability changes. Neurone specific enolase was measured before and after the stimulation to prove the safety of the stimulation protocol. RESULTS: Five and 7 min direct current stimulation resulted in motor cortical excitability reductions, which lasted for minutes after the end of stimulation, 9 min stimulation induced after-effects for up to an hour after the end of stimulation, as revealed by transcranial magnetic stimulation. Muscle evoked potentials elicited by transcranial electric stimulation and H-reflexes did not change. Neurone specific enolase concentrations remained stable throughout the experiments. CONCLUSIONS: Cathodal transcranial direct current stimulation is capable of inducing prolonged excitability reductions in the human motor cortex non-invasively. These changes are most probably localised intracortically.

Adult↗