Growth and body composition in children with classical phenylketonuria: results in 34 patients and review of the literature.

Treatment of phenylketonuria (PKU, OMIM 261600) means a diet restricted in natural protein and supplemented with phenylalanine (Phe)-free L-amino acid mixtures. Growth impairment has been described even in patients with a total protein intake at or above the recommended dietary allowance (RDA). In the present study, growth and body composition (fat-free mass (FFM) and fat) were recorded over 12 months in 34 treated PKU patients (mean age 8.7 years at baseline). Measurements were compared with those of healthy peers and with general population standard (Z-) scores calculated using the LMS method. In 28 PKU patients, data on birth weight and birth length were available and related to measurements at baseline of the study. Mean total protein intake in PKU patients was 124% (range 77-193%) of the RDA (DACH 2000). No significant differences in growth and body composition were present between PKU patients and healthy populations either at birth or during the study period. The significant correlation of FFM (representing muscle mass) with intake of natural protein--rather than total protein--indicates that the enhancement of tolerance to natural protein may be of value in PKU patients.

High resolution spatiotemporal analysis of the contingent negative variation in simple or complex motor tasks and a non-motor task.

OBJECTIVES: Since the characteristics of the Bereitschaftspotential (BP) - voluntary movement paradigm of internally-driven movements - have been established recently by our group using high resolution DC-EEG techniques, it was of great interest to apply similar techniques to the other slow brain potential--contingent negative variation (CNV) of externally-cued movements--with the same motor tasks using the same subjects. METHODS: The CNV for simple bimanual sequential movements (task 1), complex bimanual sequential movements (task 2) and a non-motor condition (task 3) was recorded on the scalp using a 64 channel DC-EEG in 16 healthy subjects, and the data were analyzed with high resolution spatiotemporal statistics and current source density (CSD). RESULTS: (1) The CNV was distributed over frontal, frontocentral, central and centroparietal regions; a negative potential was found at the frontal pole and a positive potential was found over occipital regions. (2) CNV amplitudes were higher for task 2 than for task 1, and there was no late CNV for task 3. (3) A high resolution spatiotemporal analysis revealed that during the early CNV component, statistical differences existed between the motor tasks (tasks 1 and 2) and the non-motor task (task 3), which occurred at frontocentral, central, centroparietal, parietal and parieto-occipital regions. During the late CNV component, additional significant differences were found not only between the motor tasks and the non-motor task but also between motor task 1 and task 2 at frontocentral, central and centroparietal regions. (4) Comparison of the CNV between the frontomesial cortex (situated over the supplementary/cingulate areas, SCMA) and both lateral pre-central areas (situated over the primary motor areas, MIs) showed that there was no statistically significant difference between the two cortical motor areas except for the early CNV. (5) Comparison of the CNV between the 3 tasks over the cortical motor areas showed that there were significant differences between the motor tasks and the non-motor task regarding the auditory evoked potential (AEP) and the early CNV component, and between all 3 tasks in the late CNV, the visual evoked potential (VEP(2)) and the N-P component. (6) The ranges and the densities of the CSD maps were larger and higher for complex than for simple tasks. The current sinks of the AEP and the early CNV were located at Fz, the late CNV at FCz and surrounding regions. As to be expected, current sources of the VEPs were located at the occipital lobes. The CNV was a current sink (negative) except for the VEP's main component which was a current source (positive). CONCLUSIONS: (1) The CNV topography over the scalp varied with the complexity of motor tasks and between motor and non-motor conditions. (2) The origin of the early CNV may rest in the frontal lobes, while the late CNV may stem from more extensive cortical areas including SCMA, MIs, etc. (3) The late CNV component is not identical with the BP.

Neuroimage of voluntary movement: topography of the Bereitschaftspotential, a 64-channel DC current source density study.

The Bereitschaftspotential (BP) was recorded at 56 scalp positions when 17 healthy subjects performed brisk extensions of the right index finger. Aim of the study was to contribute to our understanding of the physiology underlying the BP and, in particular, to specify the situation at BP onset. For this purpose, the spatial pattern of the BP was analyzed in short time intervals (35 and/or 70 ms) starting 2.51 s before movement onset. For each time segment a spherical model of the BP was calculated by using spline interpolation. Then the spatial distribution of the electric potential at the scalp surface was transformed into a spatial distribution of current source densities (CSD map). Onset times of the BP and onset times of initial CSD-activity ranged between 2.23 and 1.81 s before movement onset. We selected a time window between 1.6 and 1.5 s before movement onset in order to analyze the spatial CSD pattern in each subject. In 10 subjects there was a significant current sink in the scalp area located over medial-wall motor areas (pre-SMA, SMA proper and anterior cingulate cortex: electrode positions C1, C2, FCz, Cz) in the absence of a significant current sink over the primary motor cortex (MI: electrode positions C3, CP3, and CP5). In three subjects significant current sinks were present at both sites and in another three subjects a current sink only over the lateral motor cortex was observed. In one subject no significant current sinks were measured. It is concluded that there is a large group of subjects (13/17) in whom BP at onset is associated with a current sink over medial-wall motor areas. At a later time interval (0.6 to 0.5 s before movement onset), significant current sinks were found in 13 subjects in medial and in 10 subjects in lateral recordings. These data were considered to be consistent with the hypothesis that, at least in a majority of subjects, medial-wall motor areas are activated earlier than lateral motor areas when organizing the initiation of a simple self-paced movement. Surface-recordings of the EEG do not allow further specification of cortical areas, which contribute to the current sinks. But in context with the current literature of the electrophysiology of nonhuman primates and of brain imaging in humans it is suggested that SMA and anterior cingulate cortex contribute to the current sink, the fronto-central midline, and that the primary motor cortex (MI) contributes to the current sink in the scalp area, which is located above MI and closely posterior to it.

High resolution DC-EEG mapping of the Bereitschaftspotential preceding simple or complex bimanual sequential finger movement.

The present set of experiments investigated the Bereitschaftspotential (BP) preceding voluntary bimanual sequential simple (task 1) and complex movements (task 2) in supplementary/cingulate and primary motor areas (SCMA, MIs) using 64-channel direct current electroencephalography analysis in 16 right-handed healthy subjects. The results showed that: (1) onset times of BPs preceding the two tasks were significantly earlier at Cz than at C3 and C4, (2) the complex task induced significantly larger amplitudes than the simple task over the SCMA 1.1 s before EMG onset (BPI period), over the SCMA and both MIs for the BP2 period, extending from the SCMA and MIs to all frontocentral, central, centroparietal, and frontal areas during the motor potential period, (3) task difference prior to 0.96 s mainly appeared in the SCMA rather than in either MI, (4) the BP had a significantly larger amplitude in the SCMA than in the MIs, the differences being asymmetric between the left and the right hemisphere motor areas, and (5) the sinks of BP current source density (CSD) preceding the two tasks were found in the frontocentral midline; and the regions and intensities of CSD maps were larger and stronger in task 2 than they were in task I at the same times of the epoch. The results suggested that: (1) the SCMA and MIs participate in bimanual sequential simple or complex movements, (2) the SCMA appears to not only serve as a trigger command for voluntary movement but also seems to design the different motor modes, (3) the amplitude, duration, onset time, CSD region, and intensity of BP all increase with the level of complexity of the movement, (4) the greater the complexity of the action, the earlier the preparation and the larger the extent of activated neuronal populations in the SCMA, (5) activation of the SCMA occurred prior to that of the MI, and (6) the activation suggests an asymmetry between left and right MIs in simultaneous bilateral finger movement, but this asymmetry seems to be less pronounced for complex movements.

Brain potentials with old/new distinction of non-words and geometric figures.

Event-related potentials (ERPs) were recorded in a continuous memory recognition task. Readable non-words and abstract geometric figures were presented in an alternating manner with an inter-stimulus interval of 2.1 s. Probability of item repetition was 0.25, a lag of one item lay between initial presentation and repetition. OLD/NEW distinction was indicated by the subject's motor response. Using linked-mastoid electrodes for reference, material-specific hemispheric asymmetries of ERPs started 150 ms after stimulus onset in temporo-lateral and parietal recordings with ERPs elicited by non-words being lateralized to the left and those by figures to the right. Clear OLD/NEW ERP effects were found with non-words: Starting about 200-250 ms after stimulus presentation, ERPs of formerly presented (OLD) items were more positive-going in recordings over the midline than ERPs of items that were new and to be repeated (NEW). In contrast, no local OLD/NEW ERP-difference was found with figures. In some brain regions, OLD/NEW ERP-differences were larger over the left hemisphere compared to the right. This finding, however, did not differ between non-words and figures.