Diffusion kurtosis metrics as biomarkers of microstructural development: A comparative study of a group of children and a group of adults.

The most common modality of diffusion MRI used in the ageing and development studies is diffusion tensor imaging (DTI) providing two key measures, fractional anisotropy and mean diffusivity. Here, we investigated diffusional changes occurring between childhood (average age 10.3 years) and mitddle adult age (average age 54.3 years) with the help of diffusion kurtosis imaging (DKI), a recent novel extension of DTI that provides additional metrics quantifying non-Gaussianity of water diffusion in brain tissue. We performed voxelwise statistical between-group comparison of diffusion tensor and kurtosis tensor metrics using two methods, namely, the tract-based spatial statistics (TBSS) and the atlas-based regional data analysis. For the latter, fractional anisotropy, mean diffusivity, mean diffusion kurtosis, and other scalar diffusion tensor and kurtosis tensor parameters were evaluated for white matter fibres provided by the Johns-Hopkins-University Atlas in the FSL toolkit (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/Atlases). Within the same age group, all evaluated parameters varied depending on the anatomical region. TBSS analysis showed that changes in kurtosis tensor parameters beyond adolescence are more widespread along the skeleton in comparison to the changes of the diffusion tensor metrics. The regional data analysis demonstrated considerably larger between-group changes of the diffusion kurtosis metrics than of diffusion tensor metrics in all investigated regions. The effect size of the parametric changes between childhood and middle adulthood was quantified using Cohen's d. We used Cohen's d related to mean diffusion kurtosis to examine heterogeneous maturation of various fibres. The largest changes of this parameter (interpreted as reflecting the lowest level of maturation by the age of children group) were observed in the association fibres, cingulum (gyrus) and cingulum (hippocampus) followed by superior longitudinal fasciculus and inferior longitudinal fasciculus. The smallest changes were observed in the commissural fibres, forceps major and forceps minor. In conclusion, our data suggest that DKI is sensitive to developmental changes in local microstructure and environment, and is particularly powerful to unravel developmental differences in major association fibres, such as the cingulum and superior longitudinal fasciculus.

Early sensory encoding of affective prosody: neuromagnetic tomography of emotional category changes.

In verbal communication, prosodic codes may be phylogenetically older than lexical ones. Little is known, however, about early, automatic encoding of emotional prosody. This study investigated the neuromagnetic analogue of mismatch negativity (MMN) as an index of early stimulus processing of emotional prosody using whole-head magnetoencephalography (MEG). We applied two different paradigms to study MMN; in addition to the traditional oddball paradigm, the so-called optimum design was adapted to emotion detection. In a sequence of randomly changing disyllabic pseudo-words produced by one male speaker in neutral intonation, a traditional oddball design with emotional deviants (10% happy and angry each) and an optimum design with emotional (17% happy and sad each) and nonemotional gender deviants (17% female) elicited the mismatch responses. The emotional category changes demonstrated early responses (<200 ms) at both auditory cortices with larger amplitudes at the right hemisphere. Responses to the nonemotional change from male to female voices emerged later ( approximately 300 ms). Source analysis pointed at bilateral auditory cortex sources without robust contribution from other such as frontal sources. Conceivably, both auditory cortices encode categorical representations of emotional prosodic. Processing of cognitive feature extraction and automatic emotion appraisal may overlap at this level enabling rapid attentional shifts to important social cues.

Neuromagnetic oscillations to emotional faces and prosody.

Higher association cortices as well as unisensory areas can support multisensory integration [D. Senkowski et al. (2008) Trends Neurosci., 31, 401-409]. The present study investigated whether audiovisual integration of emotional information emerges early at unisensory or later at higher association cortices. Emotional stimuli were presented in three blocks: audiovisual (AV), auditory (A) and visual (V). Eighteen participants performed a delayed emotional recognition task (happy, angry or neutral prosody and/or facial expression) while whole-brain magnetoencephalography (MEG) data were obtained. Time-frequency evoked and total power analyses were performed on the sensor data, and source localization of the frequencies of interest performed via a synthetic aperture magnetometry beamformer. To examine crossmodal integration between bimodal and unimodal conditions, two contrasts were specified: AV > A and AV > V. In the AV > A contrast, early effects were observed on both the temporal and the occipital evoked responses. However, at the source level, early alpha suppression was limited to the occipital sources without changes in temporal cortices. In the AV > V contrast, sensor and source findings revealed increased alpha suppression only in temporal cortices, with no changes in visual cortex. Thus, no crossmodal effect in unisensory areas emerged. Instead, increased frontal alpha activity in both the AV > A and AV > V contrasts supports the view that affective information from face and prosody converges at higher association cortices.

Spatially congruent visual motion modulates activity of the primary auditory cortex.

We investigated the brain responses to the transitions from the static to moving audiovisual stimuli using magnetoencephalography. The spatially congruent auditory and visual stimuli moved in the same direction whereas the incongruent stimuli moved in the opposite directions. Using dipole modeling we found that the static-to-moving transitions evoked a neural response in the primary auditory cortex bilaterally. The response started about 100 ms after the motion onset from a negative component (mvN1) and lasted during the entire interval of the stimulus motion. The mvN1 component was similar to the classical auditory N1 response to the static sound, but had smaller amplitude and later latency. The coordinates of the mvN1 and N1 dipoles in the primary auditory cortex were also similar. The amplitude of the auditory response to the moving stimuli appears to be sensitive to spatial congruency of the audiovisual motion; it was larger in the incongruent than congruent condition. This is evidence that the moving visual stimuli modulate the early sensory activity in the primary auditory cortex. Such early audiovisual integration may be specific for motion processing.

An automatic procedure for the analysis of electric and magnetic mismatch negativity based on anatomical brain mapping.

Data processing techniques in electroencephalography (EEG) and magnetoencephalography (MEG) need user interactions. However, particularly in clinical applications, fast and objective data processing is important. Here we present an observer-independent method for EEG and MEG analysis of mismatch negativity (MMN) that allows reliable estimation of source activity based on objective anatomical references. The procedure integrates several steps including artifact rejection, source estimation and statistical analysis. It enables the evaluation of source activity in a fully automatic and unsupervised manner. To test its feasibility we obtained EEG and MEG responses in an auditory oddball paradigm in 12 healthy volunteers. The automatized method of EEG and MEG data analysis estimated source activity. The automatically detected MMN was closely comparable with the results obtained by a user-controlled method based on the dipole fitting. The presented workflow can be performed easily, rapidly, and reliably. This development may open new fields in research and clinical applications of source-based EEG and MEG.

Statistical Instability of TBSS Analysis Based on DTI Fitting Algorithm.

Voxel-based DTI analysis is an important approach in the comparison of subject groups by detecting and localizing gray and white matter changes in the brain. One of the principal problems for intersubject comparison is the absence of a "gold standard" processing pipeline. As a result, contradictory results may be obtained from identical data using different data processing pipelines, for example, in the data normalization or smoothing procedures. Tract-based spatial statistics (TBSS) shows potential to overcome this problem by automatic detection of white matter changes and decreasing variation in the performed analysis. However, skeleton projection approaches, such as TBSS, critically depend on the accuracy of the diffusion scalar metric estimations. In this work, we demonstrate that the agreement and reliability of TBSS results depend on the applied DTI data processing algorithm. Statistical tests have been performed using two in vivo measured datasets and compared with different implementations of the least squares algorithm. As a result, we recommend repeating TBSS analysis using different fitting algorithms, in particular, using on iteratively-assessed robust estimators, as accurate and more reliable approach in voxel-based analysis, particularly, for TBSS. Repeating TBSS analysis allows one to detect and localize suspicious regions in white matter which were estimated as the regions with significant difference. Finally, we did not find a favorite fitting algorithm (or class of them) which can be marked as more reliable for group comparison.

Hippocampus 5-HT(1A)-receptors attenuate cocaine-induced hyperlocomotion and the increase in hippocampal but not nucleus accumbens 5-HT.

Cocaine induces an increase in hippocampal and nucleus accumbens (Nac) serotonin (5-HT) concentration parallel to locomotor activation. Both effects can be modulated by systemic 5-HT(1A)-receptor agonism/antagonism. Given the contribution of the hippocampus to spontaneous behavioral activity, these observations suggest a role for hippocampal 5-HT as well in the modulation of cocaine effects on behavior. To determine the role of hippocampal 5-HT(1A)-receptors in cocaine effects on behavior and hippocampal 5-HT release, we used in vivo microdialysis in freely moving rats. The 5-HT(1A)-receptor agonist, 8-OH-DPAT (0, 0.1, 1 and 10 microM), was applied locally into the hippocampus by reversed dialysis followed by a cocaine (10 mg/kg) or saline i.p. injection. The hippocampal 5-HT(1A)-receptor activation attenuated cocaine-induced hyperlocomotion and rearing behavior dose-dependently. Parallel to that, the cocaine-induced 5-HT increase was attenuated dose-dependently in the hippocampus but was left unaffected in the Nac. The intra-hippocampal application of 8-OH-DPAT affected neither behavioral activity nor 5-HT concentration in the hippocampus and in the Nac. In accord with these findings, hippocampal 5-HT(1A)-receptors may not be directly involved in the regulation of spontaneous behavior or basal 5-HT concentration in the hippocampus and Nac. However, the results indicate an inhibitory role of hippocampal 5-HT(1A)-receptors in cocaine-induced hyperactivity and in the 5-HT increase evoked by cocaine in the hippocampus but not in the Nac.