Thomas Kammer

Long-lasting modulation of feature integration by transcranial magnetic stimulation

The human brain analyzes a visual object first by basic feature detectors. On the objects way to a conscious percept, these features are integrated in subsequent stages of the visual hierarchy. The time course of this feature integration is largely unknown. To shed light on the temporal dynamics of feature integration, we applied transcranial magnetic stimulation (TMS) to a feature fusion paradigm. In feature fusion, two stimuli which differ in one feature are presented in rapid succession such that they are not perceived individually but as one single stimulus only. The fused percept is an integration of the features of both stimuli. Here, we show that TMS can modulate this integration for a surprisingly long period of time, even though the individual stimuli themselves are not consciously perceived. Hence, our results reveal a long-lasting integration process of unconscious feature traces.

Motor thresholds in humans: a transcranial magnetic stimulation study comparing different pulse waveforms, current directions and stimulator types

OBJECTIVES To evaluate the stimulation effectiveness of different magnetic stimulator devices with respect to pulse waveform and current direction in the motor cortex. METHODS In 8 normal subjects we determined motor thresholds of transcranial magnetic stimulation in a small hand muscle. We used focal figure-of-eight coils of 3 common stimulators (Dantec Magpro, Magstim 200 and Magstim Rapid) and systematically varied current direction (postero-anterior versus antero-posterior, perpendicular to the central sulcus) as well as pulse waveform (monophasic versus biphasic). The coil position was kept constant with a stereotactic positioning device. RESULTS Motor thresholds varied consistently with changing stimulus parameters, despite substantial interindividual variability. By normalizing the values with respect to the square root of the energy of the capacitors in the different stimulators, we found a homogeneous pattern of threshold variations. The normalized Magstim threshold values were consistently higher than the normalized Dantec thresholds by a factor of 1.3. For both stimulator types the monophasic pulse was more effective if the current passed the motor cortex in a postero-anterior direction rather than antero-posterior. In contrast, the biphasic pulse was weaker with the first upstroke in the postero-anterior direction. We calculated mean factors for transforming the intensity values of a particular configuration into that of another configuration by normalizing the different threshold values of each individual subject to his lowest threshold value. CONCLUSIONS Our transformation factors allow us to compare stimulation intensities from studies using different devices and pulse forms. The effectiveness of stimulation as a function of waveform and current direction follows the same pattern as in a peripheral nerve preparation (J Physiol (Lond) 513 (1998) 571).

Proinflammatory cytokines in serum of patients with acute cerebral ischemia : kinetics of secretion and relation to the extent of brain damage and outcome of disease

The release of the proinflammatory cytokines IL-1 beta, IL-6, TNF-alpha and soluble TNF-receptors p55 and p75 in peripheral blood was serially determined in 19 patients with acute cerebral ischemia. Only patients admitted within 4 h following onset of symptoms were studied. In contrast to serum levels of IL-1 beta, TNF-alpha and TNF-receptors, which did not exhibit a significant response, IL-6 showed a significant increase of serum levels already within the first hours following onset of disease and reached a plateau at 10 h until day 3 and returned to baseline by day 7. The increase of levels of this cytokine was significantly (P < 0.05) correlated with increasing volumes of brain lesion and was also significantly (P < 0.005) associated with poor functional and neurological outcome. The increase of levels of IL-6 despite a considerable dilution in peripheral blood shown in this preliminary study suggests an early inflammatory response in ischemic brain lesion.

Electric field properties of two commercial figure-8 coils in TMS: calculation of focality and efficiency

OBJECTIVE To compare two commonly used TMS coils, namely the Medtronic MC-B70 double coil and the Magstim 70 mm double coil, with respect to their electric field distributions induced on the cortex. METHODS Electric field properties are calculated on a hemisphere representing the cortex using a spherical head model. The coil designs are characterised using several parameters, such as focality, efficiency and stimulation depth. RESULTS Medtronic and Magstim coils exhibit similar focality values and stimulation depths, despite very different coil designs. However, the Medtronic coil is about 1.2 times more efficient compared to the Magstim coil. This difference corresponds to different motor and visual phosphene thresholds obtained in previous physiological studies, thereby validating the chosen coil modelling approach. Focality of the Medtronic coil changed less with varying coil-cortex distance compared to the Magstim coil, whereas both coils exhibited similar dependencies on changes in cortex radius. CONCLUSIONS The similar values for focality and stimulation depth indicate that both coil types should evoke similar physiological effects when adjusting for the different efficiencies. The different physiological thresholds of the two coils can be traced back to differences in coil design. Ideally, focality should depend neither on coil-cortex distance nor on cortex radius in order to allow for an inter-subject comparability. In particular, in motor mapping experiments the size of the resulting maps is affected by these two parameters. Consequently, they are at least partially the cause of the variability across subjects seen in these experiments.

Linking Physics with Physiology in TMS: A Sphere Field Model to Determine the Cortical Stimulation Site in TMS

A fundamental problem of transcranial magnetic stimulation (TMS) is determining the site and size of the stimulated cortical area. In the motor system, the most common procedure for this is motor mapping. The obtained two-dimensional distribution of coil positions with associated muscle responses is used to calculate a center of gravity on the skull. However, even in motor mapping the exact stimulation site on the cortex is not known and only rough estimates of its size are possible. We report a new method which combines physiological measurements with a physical model used to predict the electric field induced by the TMS coil. In four subjects motor responses in a small hand muscle were mapped with 9-13 stimulation sites at the head perpendicular to the central sulcus in order to keep the induced current direction constant in a given cortical region of interest. Input-output functions from these head locations were used to determine stimulator intensities that elicit half-maximal muscle responses. Based on these stimulator intensities the field distribution on the individual cortical surface was calculated as rendered from anatomical MR data. The region on the cortical surface in which the different stimulation sites produced the same electric field strength (minimal variance, 4.2 +/- 0.8%.) was determined as the most likely stimulation site on the cortex. In all subjects, it was located at the lateral part of the hand knob in the motor cortex. Comparisons of model calculations with the solutions obtained in this manner reveal that the stimulated cortex area innervating the target muscle is substantially smaller than the size of the electric field induced by the coil. Our results help to resolve fundamental questions raised by motor mapping studies as well as motor threshold measurements.

The influence of current direction on phosphene thresholds evoked by transcranial magnetic stimulation

OBJECTIVES To quantify phosphene thresholds evoked by transcranial magnetic stimulation (TMS) in the occipital cortex as a function of induced current direction. METHODS Phosphene thresholds were determined in 6 subjects. We compared two stimulator types (Medtronic-Dantec and Magstim) with monophasic pulses using the standard figure-of-eight coils and systematically varied hemisphere (left and right) and induced current direction (latero-medial and medio-lateral). Each measurement was made 3 times, with a new stimulation site chosen for each repetition. Only those stimulation sites were investigated where phosphenes were restricted to one visual hemifield. Coil positions were stereotactically registered. Functional magnetic resonance imaging (fMRI) of retinotopic areas was performed in 5 subjects to individually characterize the borders of visual areas; TMS stimulation sites were coregistered with respect to visual areas. RESULTS Despite large interindividual variance we found a consistent pattern of phosphene thresholds. They were significantly lower if the direction of the induced current was oriented from lateral to medial in the occipital lobe rather than vice versa. No difference with respect to the hemisphere was found. Threshold values normalized to the square root of the stored energy in the stimulators were lower with the Medtronic-Dantec device than with the Magstim device. fMRI revealed that stimulation sites generating unilateral phosphenes were situated at V2 and V3. Variability of phosphene thresholds was low within a cortical patch of 2x2cm(2). Stimulation over V1 yields phosphenes in both visual fields. CONCLUSIONS The excitability of visual cortical areas depends on the direction of the induced current with a preference for latero-medial currents. Although the coil positions used in this study were centered over visual areas V2 and V3, we cannot rule out the possibility that subcortical structures or V1 could actually be the main generator for phosphenes.

Transcranial magnetic stimulation in the visual system. II. Characterization of induced phosphenes and scotomas

Transcranial magnetic stimulation (TMS) induces phosphenes and disrupts visual perception when applied over the occipital pole. Both the underlying mechanisms and the brain structures involved are still unclear. In the first part of this study we show that the masking effect of TMS differs to masking by light in terms of the psychometric function. Here we investigate the emergence of phosphenes in relation to perimetric measurements. The coil positions were measured with a stereotactic positioning device, and stimulation sites were characterized in four subjects on the basis of individual retinotopic maps measured by with functional magnetic resonance imaging. Phosphene thresholds were found to lie a factor of 0.59 below the stimulation intensities required to induce visual masking. They covered the segments in the visual field where visual suppression occurred with higher stimulation intensity. Both phosphenes and transient scotomas were found in the lower visual field in the quadrant contralateral to the stimulated hemisphere. They could be evoked from a large area over the occipital pole. Phosphene contours and texture remained quite stable with different coil positions over one hemisphere and did not change with the retinotopy of the different visual areas on which the coil was focused. They cannot be related exclusively to a certain functionally defined visual area. It is most likely that both the optic radiation close to its termination in the dorsal parts of V1 and back-projecting fibers from V2 and V3 back to V1 generate phosphenes and scotomas.

Mechanisms and Applications of Theta-burst rTMS on the Human Motor Cortex

Theta-burst Stimulation (TBS) is a novel form of repetitive transcranial magnetic stimulation (rTMS). Applied over the primary motor cortex it has been successfully used to induce changes in cortical excitability. The advantage of this stimulation paradigm is that it is able to induce strong and long lasting effects using a lower stimulation intensity and a shorter time of stimulation compared to conventional rTMS protocols. Since its first description, TBS has been used in both basic and clinical research in the last years and more recently it has been expanded to other domains than the motor system. Its capacity to induce synaptic plasticity could lead to therapeutic implications for neuropsychiatric disorders. The neurobiological mechanisms of TBS are not fully understood at present; they may involve long-term potentiation (LTP)- and depression (LTD)-like processes, as well as inhibitory mechanisms modulated by GABAergic activity. This article highlights current hypotheses regarding the mechanisms of action of TBS and some central factors which may influence cortical responses to TBS. Furthermore, previous and ongoing research performed in the field of TBS on the motor cortex is summarized.

The Frohlich effect: a consequence of the interaction of visual focal attention and metacontrast

Usually we assume that the central nervous system preserves temporal sequences. Here we show that moving objects--in the context of behaviour often dangerous ones--are seen with a shorter latency than stationary (flashed) objects. In addition moving objects are deblurred. Two mechanisms contribute to this functional specialisation: cue-induced visual focal attention and metacontrast. Under unnatural conditions these mechanisms lead to an optical illusion first described by Fröhlich [Fröhlich, F. W. (1923). Uber die Messung der Empfindungszeit. Zeitschrift für Sinnesphysiologie, 54, 58-78].

Electroencephalographic response to transcranial magnetic stimulation in children: Evidence for giant inhibitory potentials

The electroencephalographic response to transcranial magnetic stimulation (TMS) recently has been established as a direct parameter of motor cortex excitability. Its N100 component was suggested to reflect an inhibitory response. We investigated influences of cerebral maturation on TMS‐evoked N100 in 6‐ to 10‐year‐old healthy children. We used a forewarned reaction time (contingent negative variation) task to test the effects of response preparation and sensory attention on N100 amplitude. Single‐pulse TMS of motor cortex at 105% motor threshold intensity evoked N100 amplitudes of more than 100μV in resting children (visible in single trials), which correlated negatively with age and positively with absolute stimulation intensity. During late contingent negative variation, which involves preactivation of the cortical structures necessary for a fast response, N100 amplitude was significantly reduced. We conclude that (1) N100 amplitude reduction during late contingent negative variation provides further evidence that TMS‐evoked N100 reflects inhibitory processes, (2) response preparation and attention modulate N100, and (3) TMS‐evoked N100 undergoes maturational changes and could serve to test cortical integrity and inhibitory function in children. Parallels between the inhibitory N100 after TMS (provoking massive synchronous excitation) and the inhibitory wave component of epileptic spike wave complexes are suggested. Ann Neurol 2005