Means and standard deviations of visual early contingent negative variation (CNV) amplitudes by DAT1 and COMT.

<p>Means and standard deviations of visual early contingent negative variation (CNV) amplitudes by DAT1 and COMT.</p

Effects of DAT1 haplotype and COMT on the lateralized motor PINV – means and standard deviations.

<p>Effects of DAT1 haplotype and COMT on the lateralized motor PINV – means and standard deviations.</p

Effects of DAT1 haplotype and COMT on the lateralized motor PINV – linear regression models¹.

1<p>B = regression coefficient; SE B = standard error of the regression coefficient; beta = standardized regression coefficient.</p

Time course and topography of the motor PINV by <i>DAT1</i> haplotype.

<p><b>Top</b>: The time course of the response-locked motor PINV over the contra- and the ipsilateral motor area is shown. Negativity is up. There were no differences between the genotype groups during response preparation (contingent negative variation, CNV) after the cue (‘A’). Differences selectively affected the post-processing interval. During the button press (vertical dashed line), response selection during the P300 shadows the movement-related potentials. Thus, we calculated the lateralized motor PINV: Time course of the lateralized motor PINV when the potential over the contra- and ipsilateral motor areas is subtracted. This eliminates the symmetrically distributed parts of stimulus-related processing. Negativity is up. The peak immediately preceding the button press, which is related to the cortico-spinal command to muscle contraction, was influenced rather in the opposite direction to the motor PINV. <b>Middle</b>: Topography of the motor PINV: Isopotential line maps of the voltage topography and of the current source density (CSD) are shown, the head is presented in the top view from above, the nose is pointing upwards. Negativity and current sinks are reflected by blue areas, positivity and current sources are illustrated by red areas. Note the contralateral lateralization. <b>Bottom</b>: sLORETA source analysis results illustrating the effects of <i>DAT1</i> polymorphisms on the lateralized motor PINV: Note the stronger centro-parietal activation in Brodman areas 1–4 and 40 for the 6R–10R/6R–10R group, which is missing in the non 6R–10R/6R–10R group (marked by squares and blue arrows). Activation in the premotor area and frontal eye field (BA 6/8) was more bilateral in the non 6R–10R/6R–10R group (red arrows). The blue dipole indicates that RAP-MUSIC yielded a spatial component that showed a localization and orientation which explained the lateralized centro-parietal activation only for the 6R–10R/6R–10R group (details not shown). The crossing red lines were set to a point near the motor cortex hand area in order to illustrate the cortical activation in this area (cf. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037814#pone-0037814-g004" target="_blank">Figure 4</a>).</p

Dipole and sLORETA source analysis of influences of <i>COMT</i> and <i>DAT1</i> polymorphisms on early visual contingent negative variation (CNV).

<p><b>Left:</b> 4-dipole source model fitted on the early CNV time interval by the genetic algorithm. Equivalent dipole 4 (pink) is symmetric to equivalent dipole 3 (green); both explain the occipito-temporal visual early CNV maxima. Dipoles 1 and 2 pick up additional frontal activity and activity related to the P300/late positive complex. <b>Middle:</b> Dipole moments for the homozygous 6R–10R/Met group (highest occipito-temporal early CNV amplitudes) compared to the homozygous other/Val group (low occipito-temporal early CNV amplitudes). Colours and numbers refer to the dipole model presented on the left, there were no qualitative differences between the groups. The vertical dashed line indicates the time of the imperative stimulus ‘X’, the early CNV time interval following the cue ‘A’ (600–900 ms) is marked in orange. <b>Right:</b> sLORETA source analysis for the same two genetic groups. The dipole locations of the dipole model depicted on the left are indicated. The occipito-temporal activation around Brodman areas 19, 37 (and adjacent areas) was stronger for the homozygous 6R–10R/Met group. The crossing red lines indicate the coordinates x = 0.40, y = −0.63, z = −0.14 (pink dipole).</p

Time course and topography of the early visual contingent negative variation (CNV) by <i>DAT1</i> and <i>COMT</i> polymorphisms separately.

<p><b>Top:</b> Time course by a) <i>DAT1</i> haplotype, and b) <i>COMT</i> Val¹⁵⁸Met genotype. Negativity is indicated by upward deflections. Stimulus-locked averages are displayed, the vertical dashed line indicates the time of the button press. The visual post-processing interval is selectively and reliably affected. Only the <i>COMT</i> polymorphism seems to influence the visual N2 in the opposite direction to the visual early CNV. <b>Bottom:</b> Topography of the early CNV (600–900 ms after the cue ‘A’). Isopotential line maps are shown, negativity is illustrated by blue areas, positivity by red areas. The head is viewed from above, the nose is upwards. The small circles illustrate the position of the electrodes. Arrows mark the visual early CNV maximum. The topography appears to be unaltered by <i>DAT1</i> and <i>COMT</i> polymorphisms, but occipito-temporal early CNV amplitude is increased in the subjects with the Met/Met and the 6R–10R/6R–10R genotypes.</p

Brain areas activated in response to subjectively adjusted heat pain correlate with COMT val158met polymorphism.

<p>During subjectively similar intense heat pain perception (individual temperature in BPD 43°C in healthy controls), posterior parietal cortex (A), lateral globus pallidus (LGP; B) and the posterior cingulate cortex (PPC; C) displayed significant correlation with COMT-polymorphism. Labelling as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023658#pone-0023658-g002" target="_blank">Fig. 2</a>,* p<0.05.</p

Genetic influences on reaction times and reaction time variability (± standard deviation).

1<p>RTSD = intraindividual standard deviation of reaction times (reaction time variability).</p

Scatterplot showing the negative correlation of frontal and occipito-temporal early contingent negative variation.

<p>Scatterplot showing the negative correlation of frontal and occipito-temporal early contingent negative variation.</p

Combined effects of <i>DAT1</i> and <i>COMT</i> on lateralized motor PINV – source analysis.

<p><b>A) Spatio-temporal dipole and sLORETA source analysis of influences of </b><b><i>COMT</i></b><b> and </b><b><i>DAT1</i></b><b> polymorphisms on lateralized motor PINV</b>. <b>Left</b>: RAP-MUSIC spatial component model fitted on the motor PINV peak. For the homozygous 6R–10R/Met group (highest lateralized motor PINV amplitudes), spatial component #2 explained left lateralized motor PINV topography, while spatial component #1 eliminates additional activity related to the visual post-processing and the P300/late positive complex. In contrast, for the homozygous other/Val group low lateralized motor PINV amplitudes, no comparable activation could be found. <b>Middle</b>: Dipole moments for the homozygous 6R–10R/Met group (highest lateralized motor PINV amplitudes) compared to the homozygous other/Val group (low motor PINV amplitudes). Colours and numbers refer to the models presented on the left. The vertical dashed line indicates the time of the button press trigger. The interval of the motor PINV peak (400–600 ms after the response) is marked in orange. <b>Right</b>: sLORETA source analysis for the same two genetic groups. The location of spatial component #2 for the homozygous 6R–10R/Met group depicted on the left is indicated (coordinates x = −0.30, y = −0.12, z = 0.54). The crossing red lines were moved to the point where this dipole projects onto the cortical surface in order to illustrate the cortical activation which was explained by this spatial component. Note that there were two areas with a stronger lateralized activation for the homozygous 6R–10R/Met group, one located more frontally around Brodman areas 6 and 8 (red arrow, premotor cortex and frontal eye field); the other located more centro-parietally comprising Brodman areas 1–4 and 40 (blue arrow, motor, somatosensory and posterior parietal cortex). <b>B) Interaction between the </b><b><i>DAT1</i></b><b> haplotype and </b><b><i>COMT</i></b><b> for the lateralized motor PINV</b>. The error bars indicate the 95% confidence intervals.</p