Non-symbolic numerical distance effect in children with and without developmental dyscalculia: a parametric fMRI study.

This study investigated areas of brain activation related to non-symbolic distance effects in children with and without developmental dyscalculia (DD). We examined 15 children with DD (11.3 years) and 15 controls (10.6 years) by means of functional magnetic resonance imaging (fMRI). Both groups displayed similar behavioral performance, but differences in brain activation were observed, particularly in the supplementary motor area and the right fusiform gyrus, where children with DD demonstrated stronger activation. These results suggest that dyscalculic children engage areas attributed to higher difficulty in response selection more than control children, possibly due to a deficient development of a spatial number representation in DD.

Structural brain lesions in adolescents with congenital heart disease.

OBJECTIVES: To assess long-term neurodevelopmental outcome of adolescents with congenital heart disease after open-heart surgery and to evaluate whether deficits are associated with cerebral injury detectable on magnetic resonance imaging (MRI). STUDY DESIGN: We conducted a cohort study with longitudinal follow-up of 53 adolescents (mean age, 13.7 years; range, 11.4 to 16.9 years) who had undergone open-heart surgery with full-flow cardiopulmonary bypass during childhood and compared them with 41 age-matched controls. Assessment included conventional MRI and neurodevelopmental testing. RESULTS: MRI abnormalities were detected in 11 of the 53 patients (21%), comprising predominately white matter abnormalities and volume loss. Neurodevelopmental outcome was impaired in several domains, including neuromotor, intellectual, and executive functions, as well as visuomotor perception and integration. Adolescents with cerebral abnormalities had greater impairment in most neurodevelopmental domains compared with those without cerebral abnormalities. CONCLUSIONS: Cerebral abnormalities can be detected in a significant proportion of adolescents with corrected congenital heart disease. These abnormalities are found predominately in the white matter and are apparently of hypoxic-ischemic origin, most likely acquired during the neonatal period.

Microstructural development: organizational differences of the fiber architecture between children and adults in dorsal and ventral visual streams.

Visual perceptual skills are basically mature by the age of 7 years. White matter, however, continues to develop until late adolescence. Here, we examined children (aged 5-7 years) and adults (aged 20-30 years) using diffusion tensor imaging (DTI) fiber tracking to investigate the microstructural maturation of the visual system. We characterized the brain volumes, DTI indices, and architecture of visual fiber tracts passing through white matter structures adjacent to occipital and parietal cortex (dorsal stream), and to occipital and temporal cortex (ventral stream). Dorsal, but not ventral visual stream pathways were found to increase in volume during maturation. DTI indices revealed expected maturational differences, manifested as decreased mean and radial diffusivities and increased fractional anisotropy in both streams. Additionally, fractional anisotropy was increased and radial diffusivity was decreased in the adult dorsal stream, which can be explained by specific dorsal stream myelination or increasing fiber compaction. Adult dorsal stream architecture showed additional intra- and interhemispheric connections: Dorsal fibers penetrated into contralateral hemispheres via commissural structures and projection fibers extended to the superior temporal gyrus and ventral association pathways. Moreover, intra-hemispheric connectivity was particularly strong in adult dorsal stream of the right hemisphere. Ventral stream architecture also differed between adults and children. Adults revealed additional connections to posterior lateral areas (occipital-temporal gyrus), whereas children showed connections to posterior medial areas (posterior parahippocampal and lingual gyrus). Hence, in addition to dorsal stream myelination or fiber compaction, progressing maturation of intra- and interhemispheric connectivity may contribute to the development of the visual system.

Children with dyslexia lack multiple specializations along the visual word-form (VWF) system.

Developmental dyslexia has been associated with a dysfunction of a brain region in the left inferior occipitotemporal cortex, called the "visual word-form area" (VWFA). In adult normal readers, the VWFA is specialized for print processing and sensitive to the orthographic familiarity of letter strings. However, it is still unclear whether these two levels of occipitotemporal specialization are affected in developmental dyslexia. Specifically, we investigated whether (a) these two levels of specialization are impaired in dyslexic children with only a few years of reading experience and (b) whether this impairment is confined to the left inferior occipitotemporal VWFA, or extends to adjacent regions of the "VWF-system" with its posterior-anterior gradient of print specialization. Using fMRI, we measured brain activity in 18 dyslexic and 24 age-matched control children (age 9.7-12.5 years) while they indicated if visual stimuli (real words, pseudohomophones, pseudowords and false-fonts) sounded like a real word. Five adjacent regions of interest (ROIs) in the bilateral occipitotemporal cortex covered the full anterior-posterior extent of the VWF-system. We found that control and dyslexic children activated the same main areas within the reading network. However, a gradient of print specificity (higher anterior activity to letter strings but higher posterior activity to false-fonts) as well as a constant sensitivity to orthographic familiarity (higher activity for unfamiliar than familiar word-forms) along the VWF-system could only be detected in controls. In conclusion, analyzing responses and specialization profiles along the left VWF-system reveals that children with dyslexia show impaired specialization for both print and orthography.

White matter plasticity in the corticospinal tract of musicians: a diffusion tensor imaging study.

With the advent of diffusion tensor imaging (DTI), the study of plastic changes in white matter architecture due to long-term practice has attracted increasing interest. Professional musicians provide an ideal model for investigating white matter plasticity because of their early onset of extensive auditory and sensorimotor training. We performed fiber tractography and subsequent voxelwise analysis, region of interest (ROI) analysis, and detailed slicewise analysis of diffusion parameters in the corticospinal tract (CST) on 26 professional musicians and a control group of 13 participants. All analyses resulted in significantly lower fractional anisotropy (FA) values in both the left and the right CST in the musician group. Furthermore, a right-greater-than-left asymmetry of FA was observed regardless of group. In the musician group, diffusivity was negatively correlated with the onset of musical training in childhood. A subsequent median split into an early and a late onset musician group (median=7 years) revealed increased diffusivity in the CST of the early onset group as compared to both the late onset group and the controls. In conclusion, these DTI-based findings might indicate plastic changes in white matter architecture of the CST in professional musicians. Our results imply that training-induced changes in diffusion characteristics of the axonal membrane may lead to increased radial diffusivity as reflected in decreased FA values.

The plasticity of the superior longitudinal fasciculus as a function of musical expertise: a diffusion tensor imaging study.

Previous neuroimaging studies have demonstrated that musical expertise leads to functional alterations in language processing. We utilized diffusion tensor imaging (DTI) to investigate white matter plasticity in musicians with absolute pitch (AP), relative pitch and non-musicians. Using DTI, we analysed the fractional anisotropy (FA) of the superior longitudinal fasciculus (SLF), which is considered the most primary pathway for processing and production of speech and music. In association with different levels of musical expertise, we found that AP is characterized by a greater left than right asymmetry of FA in core fibres of the SLF. A voxel-based analysis revealed three clusters within the left hemisphere SLF that showed significant positive correlations with error rates only for AP-musicians in an AP-test, but not for musicians without AP. We therefore conclude that the SLF architecture in AP musicians is related to AP acuity. In order to reconcile our observations with general aspects of development of fibre bundles, we introduce the Pioneer Axon Thesis, a theoretical approach to formalize axonal arrangements of major white matter pathways.

Role of dorsal and ventral stream development in biological motion perception.

Little is known about the functional development of dorsal and ventral visual streams. The right posterior superior temporal sulcus (pSTS) represents a pivotal point of the two streams and is involved in the perception of biological motion. Here, we compared brain activity between children (aged 5-7 years) and adults (aged 20-32 years) while they were viewing point-light dot animations of biological motion. Biological motion-related activation was found in right pSTS of adults, and in right fusiform gyrus and left middle temporal lobe of children. Group comparisons revealed increased activity in pSTS for adults and in fusiform gyrus for children. Only poorly performing children showed fusiform gyrus activity. These findings indicate that pSTS functioning is not adult-like at the age of 6 years.

Development of neural networks for exact and approximate calculation: a FMRI study.

Neuroimaging findings in adults suggest exact and approximate number processing relying on distinct neural circuits. In the present study we are investigating whether this cortical specialization is already established in 9- and 12-year-old children. Using fMRI, brain activation was measured in 10 third- and 10 sixth-grade school children and 20 adults during trials of symbolic approximate (AP) and exact (EX) calculation, as well as non-symbolic magnitude comparison (MC) of objects. Children activated similar networks like adults, denoting an availability and a similar spatial extent of specified networks as early as third grade. However, brain areas related to number processing become further specialized with schooling. Children showed weaker activation in the intraparietal sulcus during all three tasks, in the left inferior frontal gyrus during EX and in occipital areas during MC. In contrast, activation in the anterior cingulate gyrus, a region associated with attentional effort and working memory load, was enhanced in children. Moreover, children revealed reduced or absent deactivation of regions involved in the so-called default network during symbolic calculation, suggesting a rather general developmental effect. No difference in brain activation patterns between AP and EX was found. Behavioral results indicated major differences between children and adults in AP and EX, but not in MC. Reaction time and accuracy rate were not correlated to brain activation in regions showing developmental changes suggesting rather effects of development than performance differences between children and adults. In conclusion, increasing expertise with age may lead to more automated processing of mental arithmetic, which is reflected by improved performance and by increased brain activation in regions related to number processing and decreased activation in supporting areas.

Featural and configural face processing strategies: evidence from a functional magnetic resonance imaging study.

We explored the processing mechanisms of featural and configural face information using event-related functional magnetic resonance imaging. Featural information describes the information contained in the facial parts; configural information conveys the spatial interrelationship between parts. In a delayed matching-to-sample task, participants decided whether an intact test face matched a precedent scrambled or blurred cue face. Scrambled faces primarily contain featural information whereas blurred faces preserve configural information. Scrambled cue faces evoked enhanced activation in the left fusiform gyrus, left parietal lobe, and left lingual gyrus when viewing intact test faces. Following blurred cue faces, test faces enhanced activation bilaterally in the middle temporal gyrus. The results suggest that featural and configural information is processed by following distinct neural pathways.

Dorsal stream development in motion and structure-from-motion perception.

Little is known about the neural development underlying high order visual perception. For example, in detection of structures by coherently moving dots, motion information must interact with shape-based information to enable object recognition. Tasks involving these different motion-based discriminations are known to activate distinct specialized brain areas in adults. Here, we investigate neural development of normally developing children using functional magnetic resonance imaging (fMRI) during perception of randomly moving point-light dots (RM), coherently moving dots that formed a 3D rotating object (SFM) and static dots. Perception of RM enhanced neural activity as compared with static dots in motion processing-related visual areas, including visual area 3a (V3a), and middle temporal area (hMT+) in 10 adults (age 20-30 years). Children (age 5-6 years) showed less pronounced activity in area V3a than adults. Perception of SFM induced enhanced neural activity as compared to RM in adults in the left parietal shape area (PSA), whereas children increased neural activity within dorsal (V3a) and ventral brain areas (lingual gyrus) of the occipital cortex. These findings provide evidence of neural development within the dorsal pathway. First, maturation was associated with enhanced activity in specialized areas within the dorsal pathway during RM perception (V3a) and SFM perception (PSA). Secondly, high order visual perception-related neural development was associated with a shift in neural activity from low level shape and motion specialized areas in children, including partially immature area V3a, to high order areas in the parietal lobule (PSA) in adults.

Impaired neural networks for approximate calculation in dyscalculic children: a functional MRI study.

BACKGROUND: Developmental dyscalculia (DD) is a specific learning disability affecting the acquisition of mathematical skills in children with otherwise normal general intelligence. The goal of the present study was to examine cerebral mechanisms underlying DD. METHODS: Eighteen children with DD aged 11.2 +/- 1.3 years and twenty age-matched typically achieving schoolchildren were investigated using functional magnetic resonance imaging (fMRI) during trials testing approximate and exact mathematical calculation, as well as magnitude comparison. RESULTS: Children with DD showed greater inter-individual variability and had weaker activation in almost the entire neuronal network for approximate calculation including the intraparietal sulcus, and the middle and inferior frontal gyrus of both hemispheres. In particular, the left intraparietal sulcus, the left inferior frontal gyrus and the right middle frontal gyrus seem to play crucial roles in correct approximate calculation, since brain activation correlated with accuracy rate in these regions. In contrast, no differences between groups could be found for exact calculation and magnitude comparison. In general, fMRI revealed similar parietal and prefrontal activation patterns in DD children compared to controls for all conditions. CONCLUSION: In conclusion, there is evidence for a deficient recruitment of neural resources in children with DD when processing analog magnitudes of numbers.

Maturation of luminance- and motion-defined form perception beyond adolescence: a combined ERP and fMRI study.

Abilities to discriminate forms defined by motion continue to develop throughout childhood. To investigate late development of the visual motion system, we measured brain activity with event-related EEG potentials (ERPs) and functional magnetic resonance imaging (fMRI) in groups of adolescents (15-17 years) and adults (20-30 years) during a visual form discrimination task--with forms being either defined by motion or luminance contrast. We further explored whether possible developmental changes varied with the degree of motion coherence reflecting maturation specific to global motion processing. Both the fMRI activation patterns and ERP topographies were very similar between adolescents and adults, suggesting that the basic visual networks for processing motion and form are established by the age of 15-17. The ERP response to luminance- and motion-defined forms was dominated by a posterior negativity (N1: 120-270 ms). The N1 of the motion contrast was delayed in adolescents, whereas the N1 of the static condition did not differ between groups. Since the motion-evoked N1 is thought to arise in the middle temporal area MT/V5, our results indicate that visual motion processing in MT continues to get faster, becoming still more efficient during late development. Neither the ERP nor the fMRI results revealed maturation effects specific to motion coherence. This indicates that the specific mechanisms to process global dot motion are already mature in adolescence. The present findings support the view that static perception matures earlier than dynamic perception, and that these visual systems have different developmental courses.

Quantitative diffusion tensor MR imaging of the brain: field strength related variance of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) scalars.

The objectives were to study the "impact" of the magnetic field strength on diffusion tensor imaging (DTI) metrics and also to determine whether magnetic-field-related differences in T2-relaxation times of brain tissue influence DTI measurements. DTI was performed on 12 healthy volunteers at 1.5 and 3.0 Tesla (within 2 h) using identical DTI scan parameters. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured at multiple gray and white matter locations. ADC and FA values were compared and analyzed for statistically significant differences. In addition, DTI measurements were performed at different echo times (TE) for both field strengths. ADC values for gray and white matter were statistically significantly lower at 3.0 Tesla compared with 1.5 Tesla (% change between -1.94% and -9.79%). FA values were statistically significantly higher at 3.0 Tesla compared with 1.5 Tesla (% change between +4.04 and 11.15%). ADC and FA values are not significantly different for TE=91 ms and TE=125 ms. Thus, ADC and FA values vary with the used field strength. Comparative clinical studies using ADC or FA values should consequently compare ADC or FA results with normative ADC or FA values that have been determined for the field strength used.

Contribution of proton magnetic resonance spectroscopy to the evaluation of children with unexplained developmental delay.

Developmental delay (DD) in children is a common socioeconomic problem with a prevalence of 1-2%. The cause of DD in children is often unknown, and magnetic resonance imaging plays an important role in evaluating children with DD, estimating long-term prognosis, and guiding therapeutic options. The aim of our study on children with DD was to elucidate 1) whether magnetic resonance spectroscopy (MRS) reveals abnormalities in cerebral metabolism and 2) whether there is a correlation between the cognitive performance and the concentration of brain metabolites, especially N-acetylaspartate (NAA), named in the literature a neuronal marker. Using proton MRS of deep gray and central white matter, we measured concentrations of brain metabolites in 48 children, who were aged 1 mo to 13 y and had unexplained DD [developmental quotient (DQ) between <50 and 85] and normal magnetic resonance imaging examinations, and compared them with those of 23 age-matched normal control children. Children with DD were divided into three groups: mild (DQ 76-85), moderate (DQ 51-75), and severe (DQ <50). We found no significant differences in metabolite concentrations, neither among the three groups of children with DD nor between patients and age-matched normal control children. Independent of the degree of mental retardation, the NAA concentrations of handicapped patients and normal children were comparable. We conclude that 1) brain metabolites, especially NAA, in children with unexplained DD are within normal limits, and 2) in most cases, proton MRS adds little information concerning cause of unexplained DD.

The influence of cortical maturation on the BOLD response: an fMRI study of visual cortex in children.

We performed blood oxygenation level-dependent (BOLD) functional MR imaging in 11 children younger than 5 y of age and 10 children older than 5 y of age. All but five of the children in the older age group were tested under light anesthesia. We examined the cerebral oxidative metabolism (CMRO(2)) associated with the processing of a flashed and a reversing checkerboard stimulus. These stimuli had been shown in a previous study to induce identical vascular responses. The reversing checkerboard activated twice the neuronal population of the flashed checkerboard, doubling the CMRO(2) associated with it. We compared the extent of activation for the positive BOLD response and found that it did not differ between the different age groups. We estimated the oxidative metabolism by examining the change in the local deoxyhemoglobin (HbR) concentration using Delta R2*. Because both stimuli induced the same vascular response, any increase in oxygen requirement would have to be met by the identical blood volume. Increasing CMRO(2) will therefore result in an increase in the oxygen extraction fraction (OEF), which raises the local HbR concentration. In the younger children, both checkerboard stimuli produced identical, high HbR concentrations. In the older children, the HbR concentration to the flashed stimulus was significantly lower than to the reversing stimulus. We conclude that, for identical stimuli, the oxidative energy requirement associated with the cortical processing is higher in young children than in older children because the presence of superfluous synaptic connections in the immature visual system activates a larger neuronal population.

An fMRI study of the cerebral macro network involved in 'cue invariant' form perception and how it is influenced by stimulus complexity.

We investigated the influence of stimulus complexity on the macro network of visual areas involved in 'cue invariant' form perception. Functional MRI imaging on 14 healthy, adult volunteers was performed during a two alternative forced choice (2-AFC) form discrimination task. The functional load imposed onto the visual system was varied by using simple and complex shapes. The figures were defined using a luminance, a chromatic or a motion contrast cue. The three cues activated the same visual areas in the ventral pathway, including area 'LO'. Activation of visual area 'V3v' but not area 'KO' in the dorsal pathway was observed to the motion contrast cue. The simple shapes induced a larger BOLD response in BA18 than the complex shapes, reflecting the selectivity of this region for the features in the stimuli such as edges and vertices. The brain regions yielding a larger BOLD signal to the complex shapes were areas know to be selective to the orthographic content of our complex stimuli. The processing requirement was assessed by comparing the subjects' reaction time. We found no significant difference in the reaction times to the simple and complex shapes. The reaction times to the luminance contrast cue and the chromatic contrast cue were identical but that to the motion contrast cue were 200 ms longer. This finding concurs with neurophysiological studies, reporting a longer onset latency for motion contrast stimuli. It further lends support to the idea that the motion contrast cue requires auxiliary processing by the visual areas of the dorsal pathway before entry into the ventral pathway.

The BOLD response: a new look at an old riddle.

Functional imaging has struggled for two decades to establish a quantitative link between the neuronal activity and the change in signal obtained. This review proposes a division of neuronal activity into a component relating to the electrical discharge activity and a component relating to the size of the activated neuronal population. These two components are argued to have opposing influences on the BOLD signal. The influence of these two components on the BOLD signal, are summarised in the standard model.

How much luxury is there in 'luxury perfusion'? An analysis of the BOLD response in the visual areas V1 and V2.

We re-analyzed the functional magnetic resonance imaging data from a study involving awake, adult, human volunteers in order to examine the influence of vascular density on the blood oxygenation level-dependent (BOLD) response. We employed a flashed and reversing stimulus paradigm where the latter stimulated twice the number of receptive fields and with it doubled the neuronal metabolic load (CMRO2) compared to the former stimulus. The blood flow increase to these stimuli was identical, so that differences in the BOLD response are due to differences in the oxygen extraction fraction. By comparing the BOLD response in human striate cortex (V1) and its neighbor, extra-striate area V2 to the two stimuli, we were able to determine the influence of the higher vascular density of striate cortex on the BOLD response. In striate cortex, the extent of activation, as measured by the number of activated voxels, was larger for the flashed than for the reversing stimulus. In extra-striate area V2, no such difference in the extent of activation was noted. Gauging the local concentration of HbR using deltaR2*, we found it to be significantly lower for the flashed than for the reversing checkerboard. We estimated the HbR concentration in extra-striate area V2 to be double that of striate cortex independent of the stimulus presented. A frequency distribution of the deltaR2* values for the flashed and reversing checkerboard revealed a shift consistent with an increase in the HbR concentration between areas V1 and V2. The metabolically most demanding stimulus, the reversing checkerboard was associated with the highest HbR concentration and with the largest number of voxels with a negative BOLD response.

What the little differences between men and women tells us about the BOLD response.

We analyzed the functional MRI signal of 15 men and 15 women. All had been presented with a flashed and a reversing, radial checkerboard stimulus. We investigated both positive and negative blood oxygenation level-dependent (BOLD) responses. The extent of activation and the change in the neuronal activity were examined. The former, by counting the number of activated voxels, the latter by using deltaR2* as an indicator of the change in the local deoxyhemoglobin (HbR) concentration. We examined both the positive and the negative BOLD response. Positive BOLD response: The flashed checkerboard gave rise to a larger number of activated voxels than for the reversing checkerboard. The mean number of activated pixels did not differ between men and women. The peak deltaR2* was significantly larger to the flashed than the reversing checkerboard, but did not reveal a gender-related difference. We noted an attenuation of the BOLD signal amplitude with time. This attenuation was larger in women than in men. Negative BOLD response: The attenuation was also larger for the flashed than the reversing stimulus and more pronounced in the chromatic contrast compared to the luminance contrast stimulus. The extent of activation was larger for the flashed than the reversing checkerboard, but did not differ between the sexes. The deltaR2* for the chromatic contrast checkerboard was larger in men than in women. No other significant differences were found. We conclude that the difference in the extent of activation between men and women is the result of our ability to detect activated pixels using statistical methods and not the result of a difference in the processing between the sexes.

What effect does measuring children under anesthesia have on the blood oxygenation level-dependent signal? A functional magnetic resonance imaging study of visual cortex.

We performed functional magnetic resonance measurements involving visual stimuli on 10 children. Half of the children were measured awake, the other half were measured under light Sevoflurane anesthesia corresponding to 0.5 mean alveolar concentration. Each child was presented with a flashed and a reversing checkerboard, which previous investigations have shown to induce identical increases in cerebral blood flow. The latter stimulus activated double the number of neurons as the former so that cerebral metabolic rate of oxygen consumption (CMRO(2)) was doubled, leading to an effective rise of the oxygen extraction fraction. We measured the extent of activation by counting the number of activated pixels and assessed the change in CMRO(2) by measuring the change in the local deoxyhemoglobin (HbR) concentration, using change in spin relaxivity. In both groups of children, the extent of activation was larger for the flashed than the reversing checkerboard, although the absolute number of activated voxels was smaller for the children who were measured under anesthesia. The HbR concentration was significantly higher during the presentation of the reversing compared with the flashed checkerboard. The relative change in the HbR concentration to the flashed and reversing checkerboard was the same in the children who were measured under anesthesia as in the children who were measured awake. We conclude that light levels of anesthesia may reduce the extent of activation but does not unduly influence either CMRO(2) or cerebral blood flow, thus preserving the blood oxygenation level-dependent signal amplitude.