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Developmental dyslexia is one of the most common neuropsychological disorders in children and adults. Only few data are available on the pathomechanisms of this specific dysfunction, assuming--among others--that dyslexia might be a disconnection syndrome of anterior and posterior brain regions involved in phonological and orthographic aspects of the reading process, as well as in the integration of phonemes and graphemes. Therefore, diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) were used to verify the hypothesis of altered white and gray matter structure in German dyslexic adults. DTI revealed decreased fractional anisotropy (FA) in bilateral fronto-temporal and left temporo-parietal white matter regions (inferior and superior longitudinal fasciculus). Significant correlations between white matter anisotropy and speed of pseudoword reading were found. In dyslexics, gray matter volumes (as measured by VBM) were reduced in the superior temporal gyrus of both hemispheres. So far, our results, based on a combined analysis of white and gray matter abnormalities, provide exceedingly strong evidence for a disconnection syndrome or dysfunction of cortical areas relevant for reading and spelling. Thus, we suggest that this imbalance of neuronal communication between the respective brain areas might be the crucial point for the development of dyslexia. (Contains 2 tables and 2 figures.)

Evaluating new technological developments for energy systems is becoming more and more complex. The overall application environment is a continuously growing and interconnected cyber-physical system so that analytical assessment is practically impossible to realize. Consequently, new solutions must be evaluated in simulation studies. Due to the interdisciplinarity of the simulation scenarios, various heterogeneous tools must be connected. This approach is known as co-simulation. During the last years, different approaches have been developed or adapted for applications in energy systems. In this paper, two co-simulation approaches are compared that follow generic, versatile concepts. The tool mosaik, which has been explicitly developed for the purpose of co-simulation in complex energy systems, is compared to the High Level Architecture (HLA), which possesses a domain-independent scope but is often employed in the energy domain. The comparison is twofold, considering the tools’ conceptual architectures as well as results from the simulation of representative test cases. It suggests that mosaik may be the better choice for entry-level, prototypical co-simulation while HLA is more suited for complex and extensive studies. [ABSTRACT FROM AUTHOR]

Temporal and spectral auditory processing abilities are required for efficient and unimpaired processing of speech and might thus be associated with the development of phonological and literacy skills in children. Indeed, studies with unselected children have found links between these basic auditory processing abilities and the development of phonological awareness, reading, and spelling. Additionally, associations between the processing of temporal or spectral/tonal information in music and phonological awareness/literacy have been reported, but findings concerning relations between music processing and spelling are rather sparse. To gain more insights into the specific, potentially age-dependent relevance of various temporal (e.g., rhythm, tempo) and tonal (e.g., pitch, melody) musical subdomains for phonological awareness and literacy, we adapted five music-processing tasks (three temporal, two tonal) for use with tablet computers and used them in two cross-sectional studies with German children from two age groups: Study 1 was conducted with preschool children (about 5 years of age; without formal reading and spelling instruction) and focused on associations between music processing and phonological awareness. In Study 2, third-graders (about 8 years of age) were investigated concerning relations between music processing, phonological awareness, reading comprehension, and spelling. In both studies, rhythm reproduction and pitch perception turned out to be significant predictors of phonological awareness in stepwise regression analyses. Although various associations between music processing and literacy were found for third-graders in Study 2, after phonological awareness was accounted for, only rhythm reproduction made a unique contribution to literacy skills, namely, to alphabetic spelling skills. Hence, both studies indicate that temporal (i.e., rhythm reproduction) and spectral/tonal (i.e., pitch perception) musical skills are distinctly and uniquely related to phonological awareness in children from different age groups (preschool vs. Grade 3). The finding that rhythm reproduction, an auditory temporal processing skill integrating perceptual and motor aspects of rhythm processing, was especially tightly linked to phonological awareness and literacy corroborates other findings on associations between rhythm processing and literacy development and is of interest from the viewpoint of current theories of developmental dyslexia. The potential relevance of our results for applied research concerning early diagnosis and training of literacy-related skills is discussed.

Purpose: It is unknown whether phonological deficits are the primary cause of developmental dyslexia or whether they represent a secondary symptom resulting from impairments in processing basic acoustic parameters of speech. This might be due, in part, to methodological difficulties. Our aim was to overcome two of these difficulties: the comparability of stimulus material and task in speech versus nonspeech conditions., Method: In this study, the authors (a) assessed auditory processing of German vowel center stimuli, spectrally rotated versions of these stimuli, and bands of formants; (b) used the same task for linguistic and nonlinguistic conditions; and (c) varied systematically temporal and spectral parameters inherent in the German vowel system. Forty-two adolescents and adults with and without reading disabilities participated., Results: Group differences were found for all linguistic and nonlinguistic conditions for both temporal and spectral parameters. Auditory deficits were identified in most but not all participants with dyslexia. These deficits were not restricted to speech stimuli-they were also found for nonspeech stimuli with equal and lower complexity compared with the vowel stimuli. Temporal deficits were not observed in isolation., Conclusion: These results support the existence of a general auditory processing impairment in developmental dyslexia.

It is still unclear whether phonological processing deficits are the underlying cause of developmental dyslexia, or rather a consequence of basic auditory processing impairments. To avoid methodological confounds, in the current study the same task and stimuli of comparable complexity were used to investigate both phonological and basic auditory (temporal and spectral) processing in dyslexia. German dyslexic children (Grades 3 and 4) were compared to age- and grade-matched controls in a vowel length discrimination task with three experimental conditions: In a phonological condition, natural vowels were used, differing both with respect to temporal and spectral information (in German, vowel length is phonemic, and vowel length differences are characterized by both temporal and spectral information). In a temporal condition, spectral information differentiating between the two vowels of a pair was eliminated, whereas in a spectral condition, temporal differences were removed. As performance measure, the sensitivity index d' was computed. At the group level, dyslexic children's performance was inferior to that of controls for phonological as well as temporal and spectral vowel length discrimination. At an individual level, nearly half of the dyslexic sample was characterized by deficits in all three conditions, but there were also some children showing no deficits at all. These results reveal on the one hand that phonological processing deficits in dyslexia may stem from impairments in processing temporal and spectral information in the speech signal. On the other hand they indicate, however, that not all dyslexic children might be characterized by phonological or auditory processing deficits., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We compared processing of speech and non-speech by means of the mismatch negativity (MMN). For this purpose, the MMN elicited by vowels was compared to those elicited by two non-speech stimulus types: spectrally rotated vowels, having the same stimulus complexity as the speech stimuli, and sounds based on the bands of formants of the vowels, representing non-speech stimuli of lower complexity as compared to the other stimulus types. This design allows controlling for effects of stimulus complexity when comparing neural correlates of processing speech to non-speech. Deviants within a modified multi-feature design differed either in duration or spectral property. Moreover, the difficulty to discriminate between the standard and the two deviants was controlled for each stimulus type by means of an additional active discrimination task. Vowels elicited a larger MMN compared to both non-speech stimulus types, supporting the concept of language-specific phoneme representations and the role of the participants' prior experience., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In a longitudinal study, auditory and visual temporal order thresholds (TOTs) were investigated in primary school children (N = 236; mean age at first data point = 6;7) at the beginning of Grade 1 and the end of Grade 2 to test whether rapid temporal processing abilities predict reading and spelling at the end of Grades 1 and 2. Auditory and visual TOTs differed but showed comparable developmental trajectories over 20 months. Visual TOTs were not predictive of literacy measures; auditory TOTs in Grade 1 were the best predictor. Interestingly, they were related to spelling in Grade 2 while auditory TOTs in Grade 2 were not, suggesting that rapid auditory processing abilities have a causal influence on literacy development., (© 2013 The Authors. Child Development © 2013 Society for Research in Child Development, Inc.)

This fMRI study investigated phonological vs. auditory temporal processing in developmental dyslexia by means of a German vowel length discrimination paradigm (Groth, Lachmann, Riecker, Muthmann, & Steinbrink, 2011). Behavioral and fMRI data were collected from dyslexics and controls while performing same-different judgments of vowel duration in two experimental conditions. In the temporal, but not in the phonological condition, hemodynamic brain activation was observed bilaterally within the anterior insular cortices in both groups and within the left inferior frontal gyrus (IFG) in controls, indicating that the left IFG and the anterior insular cortices are part of a neural network involved in temporal auditory processing. Group subtraction analyses did not demonstrate significant effects. However, in a subgroup analysis, participants performing low in the temporal condition (all dyslexic) showed decreased activation of the insular cortices and the left IFG, suggesting that this processing network might form the neural basis of temporal auditory processing deficits in dyslexia., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Behavioral and functional neuroimaging studies indicate deficits in verbal working memory (WM) and frontoparietal dysfunction in individuals with dyslexia. Additionally, structural brain abnormalities in dyslexics suggest a dysconnectivity of brain regions associated with phonological processing. However, little is known about the functional neuroanatomy underlying cognitive dysfunction in dyslexia. In this study, functional magnetic resonance imaging and multivariate analytic techniques were used to investigate patterns of functional connectivity during a verbal WM task in individuals with dyslexia (n=12) and control subjects (n=13). Dyslexics were not significantly slower than controls; however, they were less accurate with increasing WM demand. Independent component analysis identified 18 independent components (ICs) among which two ICs were selected for further analyses. These ICs included functional networks which were positively correlated with the delay period of the activation task in both healthy controls and dyslexics. Connectivity abnormalities in dyslexics were detected within both networks of interest: within a "phonological" left-lateralized prefrontal network, increased functional connectivity was found in left prefrontal and inferior parietal regions. Within an "executive" bilateral frontoparietal network, dyslexics showed a decreased connectivity pattern comprising bilateral dorsolateral prefrontal and posterior parietal regions, while increased connectivity was found in the left angular gyrus, the left hippocampal cortex and the right thalamus. The functional connectivity strength in the latter regions was associated with WM task accuracy and with the numbers of errors during a spelling test. These data suggest functional connectivity abnormalities in two spatiotemporally dissociable brain networks underlying WM dysfunction in individuals with dyslexia.

The article was motivated by a commentary of Spinelli et al. (2010) , who commented on our experimental study with dyslexic children (Lachmann & van Leeuwen, 2008). They questioned the unusually large reversed lexicality effect we reported for three of our dyslexic children for which word reading times were considerably longer than nonword reading times. We argued that, in principle, in a transparent orthography, such as German, children exist who have significant problems in word reading, but for whom nonword reading is normal. The extreme reversed lexically effect, however, may not be representative for the dyslexic population. Since we do not want to give the impression that our results were based on these three participants, we reran analyses on reaction times presented in Lachmann and van Leeuwen, this time excluding the data from the three individuals. Results were replicated. The constructive criticism has helped put both the diagnostics and our experimental results on even firmer ground. Both yield a consistent interpretation, in which two subgroups of dyslexics can be distinguished: one with generic activation problems; the other with a specific problem in phoneme-grapheme conversion.

Developmental dyslexia has been assumed to arise from general auditory deficits, compromising rapid temporal integration both of linguistic and nonlinguistic acoustic stimuli. Because the effort of auditory temporal processing of speech and nonspeech test materials may depend on presentation rate, fMRI measurements were performed in dyslexics and controls during passive listening to series of syllable and click sounds, using a parametric approach. Controls showed a decrease of hemodynamic brain activation within the right and an increase within the left anterior insula as a function of the presentation rate both of click as well as syllable trains. By contrast, dyslexics exhibited this profile of hemodynamic responses under the nonspeech condition only. As concerns syllables, activation in dyslexics did not depend on presentation rate. Moreover, a subtraction analysis of hemodynamic main effects across conditions and groups revealed decreased activation both of the left and right anterior insula in dyslexics compared to controls during application both of click and syllables. These results indicate, in line with preceding studies, that the insula of both hemispheres is involved in auditory temporal processing of nonlinguistic auditory stimuli and demonstrate, furthermore, that these operations of intrasylvian cortex also extend to the linguistic domain. In addition, our data suggest that the anterior insula represents an important neural correlate of deficient temporal processing of speech and nonspeech sounds in dyslexia., ((c) 2008 Wiley-Liss, Inc.)

Deficits in verbal short-term memory have been identified as one factor underlying reading and spelling disorders. However, the nature of this deficit is still unclear. It has been proposed that poor readers make less use of phonological coding, especially if the task can be solved through visual strategies. In the framework of Baddeley's phonological loop model, this study examined serial recall performance in German second-grade children with poor vs good reading and spelling abilities. Children were presented with four-item lists of common nouns for immediate serial recall. Word length and phonological similarity as well as presentation modality (visual vs auditory) and type of recall (visual vs verbal) were varied as within-subject factors in a mixed design. Word length and phonological similarity effects did not differ between groups, thus indicating equal use of phonological coding and rehearsal in poor and good readers. However, in all conditions, except the one that combined visual presentation and visual recall, overall performance was significantly lower in poor readers. The results suggest that the poor readers' difficulties do not arise from an avoidance of the phonological loop, but from its inefficient use. An alternative account referring to unstable phonological representations in long-term memory is discussed., (Copyright (c) 2007 John Wiley & Sons, Ltd.)

Behavioral studies indicate deficits in phonological working memory (WM) and executive functioning in dyslexics. However, little is known about the underlying functional neuroanatomy. In the present study, neural correlates of WM in adolescents and young adults with dyslexia were investigated using event-related functional magnetic resonance imaging (fMRI) and a parametric verbal WM task which required the manipulation of verbal material. Dyslexics were not significantly slower than controls; however, they were less accurate with the highest WM demand. The functional analysis excluded incorrectly performed and omitted trials, thus controlling for potential activation confounds. Compared with control subjects, both increased and decreased activation of the prefrontal cortex were found in the dyslexic group. Dyslexics showed significantly more activation than controls with increasing WM demand in the left superior frontal gyrus (BA 8), as well as in the inferior frontal gyrus including Broca's area (BA 44) and its right homologue. Less activation was found in the middle frontal gyrus (BA 6) and in the superior parietal cortex (BA 7). A positive correlation between activation of prefrontal regions and verbal WM performance (as measured by digit span backwards) was found only in the dyslexic group. Accuracy deficits at the highest cognitive demand during the verbal WM task and the digit span backwards suggest that manipulation rather than maintenance is selectively impaired in dyslexics. The fMRI data provide further evidence for functional differences in cortical regions associated with language processing and executive function in subjects with dyslexia.

Recent functional MRI (fMRI) studies have revealed an increased task-related activation in older subjects during a variety of cognitive or perceptual tasks, which may signal beneficial compensatory activity to counteract structural and neurochemical changes associated with aging. Under the assumption that incremental movement rates are associated with an increased functional demand on the motor system, we used fMRI and acoustically paced movements of the right index finger at six different frequencies (2.0, 2.5, 3.0, 4.0, 5.0 and 6.0 Hz) to investigate the behavioral significance of additionally recruited brain regions in a group of healthy, older subjects (mean age 66 +/- 8 years) compared with a group of young (mean age 23 +/- 7 years) subjects. The actual tapping frequency (F(1,14) = 0.049, P = 0.829), the tapping interval (F(1,14) = 0.043, P = 0.847), and the error rates (F(1,14) = 0.058, P = 0.743) did not differ significantly between both groups, whereas there was a significant increase in reaction time in the older subjects (F(1,14) = 281.786, P < or = 0.001). At all frequencies, the older subjects demonstrated significant overactivation within the ipsilateral sensorimotor and premotor cortex. However, we did not observe an increased age-related overactivation during higher movements rates in these or other motor regions. Moreover, the magnitude of the hemodynamic response in overactivated regions remained constant across all frequencies. In contrast to cognitive tasks, these findings indicate that an age-related overactivation within the motor system is not related to the functional demand and does not necessarily reflect reorganization to compensate for the neurobiological changes of aging.

This study compared three micromanual methods for determining bilirubin concentration. The two microchemical methods for total bilirubin, a Jendrassik-Grof procedure and a Unopette procedure, using dimethyl sulfoxide as an accelerator and protein solubilizer, gave comparable results in sera of adults and children. A microspectrophotometric method and the microchemical methods for total bilirubin gave similar results in plasmas of newborns with physiologic hyperbilirubinemia and in sera of older children with no hepatic abnormality. However, the microspectrophotometric method gave higher values in normal and hyperbilirubinemic adult sera. The results obtained with the Jendrassik-Grof and Unopette microchemical methods for direct bilirubin in sera of adults and children showed the values determined by the Unopette to be higher. Using the presently accepted normal range, this difference is significant enough to preclude recommendation of the use of the Unopette method for distinguishing normal from elevated levels of direct bilirubin. Direct bilirubin in newborn serum measured by the Unopette method is considerably higher than that measured by the Jendrassik-Grof method. An investigation to determine the reason for the difference in the direct bilirubin results indicated that the Unopette direct method measures diconjugated bilirubin in amounts similar to those measured by the Jendrassik-Grof method but significantly more monoconjugated bilirubin than the Jendrassik-Grof method.

The Honeywell ACS 1000, an automated computerized scanning system, is evaluated against the recommended manual method for WBC differentials. Over 400,000 data points were gathered by both methods during an 11-month study, employing routine peripheral blood smears and critically characterized control preparations. These data were found to exhibit an effective increase in throughput, precision, comparable accuracy, and a reduction in operator fatigue. In addition, the instrument demonstrates application to the improvement of quality control, teaching, and continuing education.