Effects of continuous theta-burst stimulation of the primary motor and secondary somatosensory areas on the central processing and the perception of trigeminal nociceptive input in healthy volunteers.

Noninvasive modulation of the activity of pain-related brain regions by means of transcranial magnetic stimulation promises an innovative approach at analgesic treatments. However, heterogeneous successes in pain modulation by setting reversible "virtual lesions" at different brain areas point at unresolved problems including the optimum stimulation site. The secondary somatosensory cortex (S2) has been previously identified to be involved in the perception of pain-intensity differences. Therefore, impeding its activity should impede the coding of the sensory component of pain intensity, resulting in a flattening of the relationship between pain intensity and physical stimulus strength. This was assessed using inactivating spaced continuous theta-burst stimulation (cTBS) in 18 healthy volunteers. In addition, cTBS was applied on the primary motor cortex (M1) shown previously to yield moderate and variable analgesic effects, whereas sham stimulation at both sites served as placebo condition. Continuous theta-burst stimulation flattened the relationship between brain activation and stimulus strength, mainly at S2, the insular cortex, and the postcentral gyrus (16 subjects analyzed). However, these effects were observed after inactivation of M1 while this effect was not observed after inactivation of S2. Nevertheless, both the M1 and the S2-spaced cTBS treatment were not reflected in the ratings of the nociceptive stimuli of different strengths (17 subjects analyzed), contrasting with the clear coding of stimulus strength by these data. Hence, while modulating the central processing of nociceptive input, cTBS failed to produce subjectively relevant changes in pain perception, indicating that the method in the present implementation is still unsuitable for clinical application.

A Data-Driven Approach to Responder Subgroup Identification after Paired Continuous Theta Burst Stimulation.

Background: Modulation of cortical excitability by transcranial magnetic stimulation (TMS) is used for investigating human brain functions. A common observation is the high variability of long-term depression (LTD)-like changes in human (motor) cortex excitability. This study aimed at analyzing the response subgroup distribution after paired continuous theta burst stimulation (cTBS) as a basis for subject selection. Methods: The effects of paired cTBS using 80% active motor threshold (AMT) in 31 healthy volunteers were assessed at the primary motor cortex (M1) corresponding to the representation of the first dorsal interosseous (FDI) muscle of the left hand, before and up to 50 min after plasticity induction. The changes in motor evoked potentials (MEPs) were analyzed using machine-learning derived methods implemented as Gaussian mixture modeling (GMM) and computed ABC analysis. Results: The probability density distribution of the MEP changes from baseline was tri-modal, showing a clear separation at 80.9%. Subjects displaying at least this degree of LTD-like changes were n = 6 responders. By contrast, n = 7 subjects displayed a paradox response with increase in MEP. Reassessment using ABC analysis as alternative approach led to the same n = 6 subjects as a distinct category. Conclusion: Depressive effects of paired cTBS using 80% AMT endure at least 50 min, however, only in a small subgroup of healthy subjects. Hence, plasticity induction by paired cTBS might not reflect a general mechanism in human motor cortex excitability. A mathematically supported criterion is proposed to select responders for enrolment in assessments of human brain functional networks using virtual brain lesions.

Identification of Molecular Fingerprints in Human Heat Pain Thresholds by Use of an Interactive Mixture Model R Toolbox (AdaptGauss).

Biomedical data obtained during cell experiments, laboratory animal research, or human studies often display a complex distribution. Statistical identification of subgroups in research data poses an analytical challenge. Here were introduce an interactive R-based bioinformatics tool, called "AdaptGauss". It enables a valid identification of a biologically-meaningful multimodal structure in the data by fitting a Gaussian mixture model (GMM) to the data. The interface allows a supervised selection of the number of subgroups. This enables the expectation maximization (EM) algorithm to adapt more complex GMM than usually observed with a noninteractive approach. Interactively fitting a GMM to heat pain threshold data acquired from human volunteers revealed a distribution pattern with four Gaussian modes located at temperatures of 32.3, 37.2, 41.4, and 45.4 °C. Noninteractive fitting was unable to identify a meaningful data structure. Obtained results are compatible with known activity temperatures of different TRP ion channels suggesting the mechanistic contribution of different heat sensors to the perception of thermal pain. Thus, sophisticated analysis of the modal structure of biomedical data provides a basis for the mechanistic interpretation of the observations. As it may reflect the involvement of different TRP thermosensory ion channels, the analysis provides a starting point for hypothesis-driven laboratory experiments.

Rapid serial processing of natural scenes: color modulates detection but neither recognition nor the attentional blink.

The exact function of color vision for natural-scene perception has remained puzzling. In rapid serial visual presentation (RSVP) tasks, categorically defined targets (e.g., animals) are detected typically slightly better for color than for grayscale stimuli. Here we test the effect of color on animal detection, recognition, and the attentional blink. We present color and grayscale RSVP sequences with up to two target images (animals) embedded. In some conditions, we modify either the hue or the intensity of each pixel. We confirm a benefit of color over grayscale images for animal detection over a range of stimulus onset asynchronies (SOAs), with improved hit rates from 50 to 120 ms and overall improved performance from 90 to 120 ms. For stimuli in which the hue is inverted, performance is similar to grayscale for small SOAs and indistinguishable from original color only for large SOAs. For subordinate category discrimination, color provides no additional benefit. Color and grayscale sequences show an attentional blink, but differences between color and grayscale are fully explained by single-target differences, ruling out the possibility that the color benefit is purely attentional.