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Biomedical subjects

Martin Sommer

Publications and source records attributed to Martin Sommer.

16 recordsLinked to original sources

Half sine, monophasic and biphasic transcranial magnetic stimulation of the human motor cortex.

OBJECTIVE: To compare half sine transcranial magnetic stimuli (TMS) with conventional monophasic and biphasic stimuli, measuring resting and active motor threshold, motor evoked potential (MEP) input/output curve, MEP latency, and silent period duration. METHODS: We stimulated the dominant hand representation of the motor cortex in 12 healthy subjects utilising two different MagPro stimulators to generate TMS pulses of distinct monophasic, half sine and biphasic shape with anteriorly or posteriorly directed current flow. RESULTS: The markedly asymmetric monophasic pulse with a posterior current flow in the brain yielded a higher motor threshold, a less steep MEP input/output curve and a longer latency than all other TMS types. Similar but less pronounced results were obtained with a less asymmetric half sine pulses. The biphasic stimuli yielded the lowest motor threshold and a short latency, particularly with the posterior current direction. CONCLUSIONS: The more asymmetric the monophasic pulse, the stronger the difference to biphasic pulses. The 3rd and 4th quarter cycle of the biphasic waveform make it longer than any other waveform studied here and likely contribute to lowering motor threshold, shortening MEP latency and reversing the influence of current direction. SIGNIFICANCE: This systematic comparison of 3 waveforms and two current directions allows a better understanding of the mechanisms of TMS.

Adult↗

Orientation-specific fast rTMS maximizes corticospinal inhibition and facilitation.

Specific stimulation of neuronal circuits may promote selective inhibition or facilitation of corticospinal tract excitability. Monophasic stimulation is more likely to achieve direction-specific neuronal excitation. In 10 healthy subjects, we compared four types of repetitive transcranial magnetic stimulation (rTMS), monophasic and biphasic stimuli with the initial current in the brain flowing antero-posteriorly ("posteriorly directed") or postero-anteriorly ("anteriorly directed"). We applied rTMS over the primary motor cortex contralateral to the dominant hand, using 80 stimuli at 5 Hz frequency at an intensity yielding baseline motor evoked potential (MEP) amplitudes of 1 mV. Monophasic stimulation was always more efficient than biphasic. Facilitation was induced by intracerebral anteriorly directed current flow and inhibition by posteriorly oriented current flow, although only initially for approximately 30 pulses. The early inhibition was absent when studied during a tonic muscle contraction. Several mechanisms could account for these findings. They include a more efficient excitation of inhibiting circuits by posteriorly oriented pulses, and a back-propagating D-wave inhibiting early I-waves and thus inducing early inhibition of MEP amplitude. In any case biphasic rTMS results can be explained by a mixture of monophasic opposite stimulations. We propose the use of monophasic pulses for maximizing effects during rTMS.

Adult↗

An organizational model of transcription factor binding sites for a histone promoter in D. melanogaster.

The Drosophila H2A-H2B histone spacer, a small region that functions as a bidirectional promoter for the gene pair, was used as a test sequence for generation of a computationally derived organizational model of transcription factor (TF) binding sites. Expression studies of the spacer revealed that it contains the necessary sequences to confer replication-dependent transcription in partially synchronized cells in culture. Informatics analysis of the spacer uncovered a number of binding sites for specific TFs, none of which had been previously associated with this particular promoter. Each of the TFs in the promoter organizational model are also known to participate in stages of fly development that are characterized by DNA replication and/or cell division, thus providing a biologically functional rationale for an association. Moreover, phylogenetic analysis of the binding sites provides evidence for evolutionary conservation of the essential features of the organizational model. The model, if correct, provides information about the molecules that couple developmental specific demands and histone gene transcription.

Animals↗

Normal intracortical excitability in developmental stuttering.

Persistent developmental stuttering (PDS) shares clinical features with task-specific dystonias. In these dystonias, intracortical inhibition is abnormally weak. We therefore sought to determine intracortical inhibition and intracortical facilitation in PDS. In 18 subjects with PDS since childhood (mean age, 39.4 [SD 13.0] years) and 18 speech-fluent controls (43.6 [14.3] years), we investigated resting and active motor thresholds as well as intracortical inhibition and facilitation of the optimal representation of the abductor digiti minimi of the dominant hand using transcranial magnetic stimulation. In PDS, the resting and active motor thresholds were increased, whereas intracortical inhibition and facilitation were normal. Normal intracortical excitability makes a pathophysiological analogy between focal dystonia and PDS less likely. The enhanced motor threshold suggests reduced motor cortical neuronal membrane excitability in PDS.

Adult↗

Pulse configuration-dependent effects of repetitive transcranial magnetic stimulation on visual perception.

Transcranial magnetic stimulation (TMS) is a noninvasive technique for direct stimulation of the neocortex. In the last two decades it is successfully applied in the study of motor and sensory physiology. TMS uses the indirect induction of electrical fields in the brain generated by intense changes of magnetic fields applied to the scalp. It encompasses two widely used waveform configurations: mono-phasic magnetic pulses induce a single current in the brain while biphasic pulses induce at least two currents of inverse direction. As has been shown for the motor cortex, efficacy of repetitive transcranial magnetic stimulation (rTMS) may depend on pulse configuration. In order to clarify this question with regard to visual perception, static contrast sensitivities (sCS) were evaluated before, during, immediately after and 10 minutes after monophasic and biphasic low frequency (1 Hz) rTMS applied to the occipital cortex of 15 healthy subjects. The intensity of stimulation was the phosphene threshold of each individual subject. Using 4 c/d spatial frequency, significant sCS loss was found during and immediately after 10 min of monophasic stimulation, while biphasic stimulation resulted in no significant effect. Ten minutes after the end of stimulation, the sCS values were at baseline level again. However, reversed current flow direction resulted in an increased efficacy of biphasic and decreased efficacy of monophasic stimulation. Our results are in agreement with previous findings showing that primary visual functions, such as contrast detection, can be transiently altered by low frequency transcranial magnetic stimulation. However the effect of modulation significantly depends on the current waveform and direction.

Adult↗

Disconnection of speech-relevant brain areas in persistent developmental stuttering.

BACKGROUND: The neuronal basis of persistent developmental stuttering is unknown. The disorder could be related to a reduced left hemisphere dominance, which functional neuroimaging data suggest might lead to right hemispheric motor and premotor overactivation. Alternatively, the core deficit underlying stuttering might be located in the speech-dominant left hemisphere. Furthermore, magnetoencephalography study results show profound timing disturbances between areas involved in language preparation and execution in the left hemisphere, suggesting that persistent developmental stuttering might be related to impaired neuronal communication, possibly caused by a disruption of white matter fibre tracts. We aimed to establish whether disconnection between speech-related cortical areas was the structural basis of persistent developmental stuttering. METHODS: We analysed the speech of 15 people with persistent developmental stuttering and 15 closely matched controls for the percentage of syllables stuttered. We used diffusion tensor imaging to assess participants' brain tissue structure, and used and two-sample t test to compare diffusion characteristics between groups. FINDINGS: Diffusion characteristics of the group with persistent developmental stuttering and controls differed significantly immediately below the laryngeal and tongue representation in the left sensorimotor cortex (mean difference in fractional anisotropy 0.04 [95% CI 0.03-0.05]). INTERPRETATION: Our findings show that persistent developmental stuttering results from disturbed timing of activation in speech-relevant brain areas, and suggest that right hemisphere overactivation merely reflects a compensatory mechanism, analogous to right hemisphere activation in aphasia.

Adult↗

Neuronal tissue polarization induced by repetitive transcranial magnetic stimulation?

In a blinded cross-over design, 10 healthy controls received 900 monophasic and biphasic repetitive transcranial magnetic stimuli over the primary motor cortex. Stimulation frequency was 1 Hz, and stimulation intensity 90% of the individual resting motor threshold. Suprathreshold stimuli applied at 0.1 Hz before and after repetitive stimulation controlled for changes in corticospinal excitability. We found a lasting corticospinal inhibition that was significantly more pronounced after monophasic than after biphasic repetitive transcranial magnetic stimulation (motor evoked potential amplitude reduced by 35 +/- 20% vs 12 +/- 37%, mean+/- s.d.). We propose that the current flow in the coil plays a significant role in optimising after effects, and asymmetric current flow may be particularly efficient in building up tissue polarization.

Adult↗

Intracortical excitability in the hand motor representation in hand dystonia and blepharospasm.

We sought to determine the activity of inhibiting and facilitating cortical circuits in areas surrounding a hand muscle motor representation in focal dystonia and in controls. In 15 patients with hand dystonia, 16 patients with blepharospasm, and age-matched controls, we applied suprathreshold transcranial magnetic stimuli with a figure-eight coil over the optimal representation of the relaxed abductor digiti minimi muscle of the dominant hand. Additional conditioning stimuli were given through a second figure-eight coil that was held either above the test coil or 2 cm or 4 cm apart in the anterior, posterior, lateral, or medial direction. We measured intracortical excitability in each of the nine positions of the conditioning coil. Intracortical inhibition was reduced in both patient groups at all conditioning coil positions. With both coils centered, the intracortical facilitation did not differ between patients and controls. After shifting the conditioning coil, the intracortical facilitation tended to be less diminished in patients than in controls, this difference between patients and controls was significant for the anterior, posterior, and medial 4-cm conditioning coil shift. Our results demonstrate decreased intracortical inhibition in the cortical hand muscle representation not only in patients with hand dystonia, but also in patients with blepharospasm. In addition, our findings in both patient groups show a trend toward a relatively increased intracortical facilitation in surrounding motor areas.

Adult↗

Increased transcranial magnetic motor threshold after ECT. A case report.

Electroconvulsive therapy (ECT) is a powerful antidepressive treatment, but its mechanism of action remains poorly understood. To clarify the influence of ECT on corticospinal tract excitability we tested the motor threshold, the motor evoked potential (MEP) input/output curve, and the intracortical excitability using transcranial magnetic stimulation in a depressed patient before and after successful treatment with ECT. Resting motor thresholds were increased bilaterally after treatment, and the input/output curve less steep. These results point to a decreased excitability of the corticospinal motor tract after successful ECT.

Aged↗

Inverse correlation of intracortical inhibition and brain-stem inhibition in humans.

OBJECTIVE: To determine whether intracortical inhibition and the conditioned blink reflex R2 inhibition correlate in healthy subjects. BACKGROUND: In Parkinson's disease and in focal dystonia the intracortical inhibition and the conditioned blink reflex R2 inhibition are abnormally weak. METHODS: In 10 healthy humans (average age 25.7 years) we investigated the intracortical excitability of the optimal representation of the abductor digiti minimi of the dominant hand using transcranial magnetic stimulation with a conditioning pulse (90% active motor threshold) followed by a pulse of 120% resting motor threshold after an interstimulus interval ranging from 1 to 30 ms. We investigated the blink reflex with two suprathreshold stimuli over the supraorbital nerve and EMG recording from the orbicularis oculi ipsilateral to electrical stimulation, the interstimulus intervals were 100, 250 and 500 ms. RESULTS: The intracortical inhibition, but not the intracortical facilitation, was inversely and significantly correlated with the R2 inhibition on the side of transcranial stimulation, but not with the contralateral R2 inhibition. CONCLUSIONS: The correlation of intracortical inhibitory interneurons and ipsilateral blink reflex interneurons may indicate a common influence, possibly from the basal ganglia, on either circuit, or a direct influence of cortical circuits on brain-stem circuits via corticopontine pathways.

Adolescent↗

Repetitive paired-pulse transcranial magnetic stimulation affects corticospinal excitability and finger tapping in Parkinson's disease.

OBJECTIVES: To study the effect of long trains of a recently established conditioning-test paired-pulse repetitive transcranial magnetic stimulation (rTMS) paradigm on corticospinal excitability and finger tapping speed. METHODS: We applied 900 inhibiting or facilitating paired-pulses or 900 real or sham single stimuli at 1Hz over the motor cortex contralateral to the dominant hand of 9 healthy subjects and contralateral to the more affected hand of 11 patients with Parkinson's disease. RESULTS: In both groups, motor evoked potentials (MEPs) from suprathreshold pulses were larger after facilitating paired-pulses than after inhibiting paired-pulses. After real single-pulse rTMS and after either type of paired-pulse rTMS patients showed an increase in finger tapping frequency on the stimulated hand. Tapping was unchanged contralaterally, after sham stimuli, and in controls. Tremor and tapping frequencies were not correlated, nor was the change in MEP size correlated to the change in tapping frequency. CONCLUSIONS: Repetitive paired-pulses allow selective induction of corticospinal inhibition or facilitation, but do not enhance the transient improvement of finger motility induced by conventional single-pulse rTMS.

Adult↗

Array-based multiplexed screening and quantitation of human cytokines and chemokines.

HydroGel-coated slide is a porous substrate based on a polymer matrix that provides a three-dimensional hydrophilic environment similar to free solution suitable for biomolecular interactions. This substrate has been used to develop fluorescence-based multiplexed cytokine immunoassays. Forty-three monoclonal antibodies (mAb) of cytokines and chemokines were printed at a volume of 350 pL per spot using a Packard BioChip Arrayer. For each probe, four replicates were printed at a pitch of 500 microm in the layout of a 13 x 16 pattern on a 12 x 12 mm2 HydroGel pad. Cytokines and chemokines that are captured by the arrayed mAbs are detected by using another biotinylated mAb, following by the addition of a Texas Red-conjugated streptavidin. The fluorescent images of arrays were recorded using a Packard ScanArray 5000 confocal slide scanner and quantitated using Packard QuantArray software. Experiments demonstrated that 43 cytokines and chemokines could be simultaneously screened and quantitated in conditioned culture media, cell lysates, and human plasma. Using this chip, we have examined cytokine expression in breast cancer cells and identified the chemokines associated with human cervical cancers.

Breast Neoplasms↗