Children at risk for dyslexia show deficient left-hemispheric memory representations for new spoken word forms.

Developmental dyslexia is a specific learning disorder with impairments in reading and spelling acquisition. Apart from literacy problems, dyslexics show inefficient speech encoding and deficient novel word learning, with underlying problems in phonological processing and learning. These problems have been suggested to be related to deficient specialization of the left hemisphere for language processing. To examine this possibility, we tracked with magnetoencephalography (MEG) the activation of the bilateral temporal cortices during formation of neural memory traces for new spoken word forms in 7-8-year-old children with high familial dyslexia risk and in controls. The at-risk children improved equally to their peers in overt repetition of recurring new word forms, but were poorer in explicit recognition of the recurring word forms. Both groups showed reduced activation for the recurring word forms 400-1200 ms after word onset in the right auditory cortex, replicating the results of our previous study on typically developing children (Nora et al., 2017, Children show right-lateralized effects of spoken word-form learning. PLoS ONE 12(2): e0171034). However, only the control group consistently showed a similar reduction of activation for recurring word forms in the left temporal areas. The results highlight the importance of left-hemispheric phonological processing for efficient phonological representations and its disruption in dyslexia.

Dynamic Time-Locking Mechanism in the Cortical Representation of Spoken Words.

Human speech has a unique capacity to carry and communicate rich meanings. However, it is not known how the highly dynamic and variable perceptual signal is mapped to existing linguistic and semantic representations. In this novel approach, we used the natural acoustic variability of sounds and mapped them to magnetoencephalography (MEG) data using physiologically-inspired machine-learning models. We aimed at determining how well the models, differing in their representation of temporal information, serve to decode and reconstruct spoken words from MEG recordings in 16 healthy volunteers. We discovered that dynamic time-locking of the cortical activation to the unfolding speech input is crucial for the encoding of the acoustic-phonetic features of speech. In contrast, time-locking was not highlighted in cortical processing of non-speech environmental sounds that conveyed the same meanings as the spoken words, including human-made sounds with temporal modulation content similar to speech. The amplitude envelope of the spoken words was particularly well reconstructed based on cortical evoked responses. Our results indicate that speech is encoded cortically with especially high temporal fidelity. This speech tracking by evoked responses may partly reflect the same underlying neural mechanism as the frequently reported entrainment of the cortical oscillations to the amplitude envelope of speech. Furthermore, the phoneme content was reflected in cortical evoked responses simultaneously with the spectrotemporal features, pointing to an instantaneous transformation of the unfolding acoustic features into linguistic representations during speech processing.

Optimal spatial filtering for brain oscillatory activity using the Relevance Vector Machine.

Over the past decade, various techniques have been proposed for localization of cerebral sources of oscillatory activity on the basis of magnetoencephalography (MEG) or electroencephalography recordings. Beamformers in the frequency domain, in particular, have proved useful in this endeavor. However, the localization accuracy and efficacy of such spatial filters can be markedly limited by bias from correlation between cerebral sources and short duration of source activity, both essential issues in the localization of brain data. Here, we evaluate a method for frequency-domain localization of oscillatory neural activity based on the relevance vector machine (RVM). RVM is a Bayesian algorithm for learning sparse models from possibly overcomplete data sets. The performance of our frequency-domain RVM method (fdRVM) was compared with that of dynamic imaging of coherent sources (DICS), a frequency-domain spatial filter that employs a minimum variance adaptive beamformer (MVAB) approach. The methods were tested both on simulated and real data. Two types of simulated MEG data sets were generated, one with continuous source activity and the other with transiently active sources. The real data sets were from slow finger movements and resting state. Results from simulations show comparable performance for DICS and fdRVM at high signal-to-noise ratios and low correlation. At low SNR or in conditions of high correlation between sources, fdRVM performs markedly better. fdRVM was successful on real data as well, indicating salient focal activations in the sensorimotor area. The resulting high spatial resolution of fdRVM and its sensitivity to low-SNR transient signals could be particularly beneficial when mapping event-related changes of oscillatory activity.

A method for spatiotemporal mapping of event-related modulation of cortical rhythmic activity.

Cortical rhythmic activity can be systematically modulated by stimuli or tasks and may thus provide relevant information about brain function. Meaningful use of those phenomena requires characterization of both locations and time courses of event-related suppressions and increases of oscillatory activity. However, localization of the neural sources of cortical rhythms during intervals of very low levels of activity, and within short time intervals, is not a trivial matter. Hence, event-related modulation of rhythmic activity has typically been described at the level of magnetoencephalography (MEG) sensors or electroencephalography (EEG) electrodes, without reaching into the brain. Here, we introduce erDICS, an event-related version of Dynamic Imaging of Coherent Sources that allows spatial mapping of the level of oscillatory activity in the brain as a function of time, with respect to stimulus or task timing. By utilizing a time-resolved frequency-domain beamformer, erDICS yields the spatial distribution of both power suppressions and power increases. Permutation tests further reveal areas and time windows in which the modulations of oscillatory power are statistically significant, in individual subjects. We demonstrate the usability of erDICS on simulated and real MEG data. From the erDICS maps we identify areas showing salient event-related changes of rhythmic activity, represent them with equivalent current dipoles and calculate their contribution to the measured signal. Comparison of this multidipole model with the original signal yields a quantitative measure of goodness for the identified source areas and the analysis approach in general.

Perceiving and naming actions and objects.

Neuropsychological studies have suggested differences in the cortical representations of verbs and nouns. Assessment of word-class specific deficits often relies on picture naming with different sets of images used for action and object naming. Such a setup may be problematic in neuroimaging studies, as the perception of the image and the actual differences in retrieving verbs or nouns become intertwined. To address this issue, we investigated how different sets of images affect the pattern of activation in action and object naming. In the present fMRI experiment, healthy volunteers silently performed both action and object naming from action images, and object naming from object-only images. A similar network of cortical areas was activated in all three conditions, including bilateral occipitotemporal and parietal regions, and left frontal cortex. With action images, noun retrieval enhanced activation in bilateral parietal and right frontal cortex, areas previously associated with visual search and attention. Increased activation in the left posterior parietal cortex during this condition also suggests that naming an object in the context of action emphasizes motor-based properties of objects. Action images, regardless of whether verbs or nouns were named, evoked stronger activation than object-only images in the posterior middle temporal cortex bilaterally, the left temporo-parietal junction, and the left frontal cortex, a network previously identified in processing of action knowledge. The strong influence of perceptual input on neural activation associated with noun vs. verb naming can in part explain discrepancies in previous lesion and functional neuroimaging studies on the processing of nouns and verbs.

Heliotherapy improves vitamin D balance and atopic dermatitis.

BACKGROUND: Vitamin D insufficiency during winter is common in the Nordic countries. Heliotherapy (HT) may heal atopic dermatitis (AD) but its effect on vitamin D balance has not been examined. OBJECTIVES: To study the effect of HT on serum calcidiol (25-hydroxyvitamin D) concentration and on healing of AD. METHODS: Twenty-three adult patients with AD received a 2-week course of HT in the Canary Islands in either January or March 2005. Daily solar ultraviolet (UV) radiation was measured and personal UV exposure calculated as standard erythema doses (SED). Blood samples were taken during HT and during a 1-2 month follow-up. Serum calcidiol concentration was measured by radioimmunoassay. Healing of AD was examined by SCORAD index. RESULTS: Before HT 17 (74%) AD patients had vitamin D insufficiency (calcidiol < 50 nmol L(-1)) and four patients high (> 80 nmol L(-1)) serum calcidiol values. The median personal UV dose during the 2-week HT course was 60 SED in the January group and 109 SED in the March group. Serum calcidiol concentration increased significantly in both groups, by 13.4 and 24.0 nmol/L(-1), respectively, and after HT only four (17%) patients had vitamin D insufficiency. SCORAD improved from 34 to 9 in the January HT group and from 30 to 9 in the March group. CONCLUSIONS: A 2-week course of HT significantly improved vitamin D balance by increasing serum calcidiol concentration, and caused a marked healing of AD. These parallel positive responses should be taken into account when the benefits of HT are considered.

Parafoveal-on-foveal and foveal word priming are different processes: behavioral and neurophysiological evidence.

Parafoveal-on-foveal priming refers to the presentation of an item (the prime) in parafoveal vision followed by the presentation of an item (the target) in foveal vision. In natural reading, the 'parafoveal preview benefit' subserves fluent reading as, e.g., reading times increase when such information is not available. Yet, the neural correlates of reading are mostly studied with foveally presented stimuli and little is known of this parafoveal influence. Here, we used complementary information from a behavioral study and a magnetoencephalography experiment to clarify the relationship between parafoveal-on-foveal and foveal priming. Unlike foveal priming, parafoveal-on-foveal priming was present only at short prime-to-target delay (<100 ms). Behaviorally, the parafoveal priming effect was influenced by the prime visual field (left/right) and target lexical type (word/non-word), suggesting emphasis on perceptual analysis for LVF primes and on conceptual analysis for RVF primes. At the neural level, the overall sequence of activation was similar for foveal and parafoveal primes followed by foveal word targets, but the priming effects were bilateral for foveal primes versus left-lateralized for RVF primes. No neural effects of priming appeared for LVF primes, in line with the RVF preference imposed by the Western writing system. These results highlight the role of the left hemisphere in linguistic analysis and point out possible limitations of foveal stimulus presentation for drawing conclusions about natural reading.

Visits by the family to the neonatal intensive care unit.

AIM: To investigate visiting frequency of family members, including mother, father, siblings and grandparents and associated factors during hospitalisation of preterm infants. METHODS: The study included all premature (< 37 weeks) infants born in Tampere University Hospital in 1997-1998 admitted to the neonatal intensive care unit (NICU) with a birth weight less than 2500 g (n = 210). Maternal and infant data and visits made by family members were compiled from the infants' hospital records. RESULTS: The length of the infants' hospitalisation varied from 2 to 133 days (median 26, quartiles 19, 45). Mothers visited the NICU on average 6.7 days/week; fathers 4.8 days/week. Mothers visited less frequently the lower the gestational age and the longer the distance between home and hospital. Fathers visited less frequently if distance from home to hospital was longer and if the infant had siblings. A total of 92% of siblings and 80% of grandparents visited the hospital. CONCLUSIONS: The results showed active visiting by the parents in the NICU. A lower gestational age was associated with lower visiting frequency for mothers. In contrast, more practical limitations such as geographical distance and other children to be taken care of had greater effect on the visiting frequency for fathers.

Etoricoxib pre-medication for post-operative pain after laparoscopic cholecystectomy.

BACKGROUND: Etoricoxib alleviates and prevents acute pain. The hypothesis of our study was that the pre-operative use of etoricoxib would reduce the post-operative need for additional pain treatment. METHODS: In this double-blind, randomized and active placebo-controlled study, 75 patients were pre-medicated 1.5 h before elective laparoscopic cholecystectomy with 120 mg of etoricoxib (E120 group), the same dose of etoricoxib combined with 1 g of paracetamol (E + P group) or placebo (Pla group). To alleviate post-operative pain, a patient-controlled analgesia (PCA) device was programmed to deliver 50 microg of fentanyl intravenously (lockout time, 5 min). The pain intensity and nausea were assessed using a visual analogue scale (VAS). The number of patients with post-operative nausea and vomiting was recorded. Blood loss was compared between the groups. Because the operations are almost blood-less, the operation time was also recorded to compare the possible effect on bleeding time. RESULTS: Pre-medication with etoricoxib or etoricoxib plus paracetamol had a statistically significant fentanyl-sparing effect 2-20 h post-operatively compared with placebo (P = 0.001). No significant differences were demonstrated in fentanyl-sparing effect between the E120 and E + P groups. No significant differences in pain intensity were found between the three study groups. No significant differences were observed between the groups with regard to nausea, blood loss, duration of anaesthesia or duration of surgery. CONCLUSION: Etoricoxib is suitable for pre-medication before laparoscopic cholecystectomy as it reduces the need for post-operative opioids. Opioid-related side-effects, however, were not reduced in the present study, despite the observed opioid-sparing effect of etoricoxib and combined etoricoxib and paracetamol.

Neuromagnetic responses to vowels vs. tones reveal hemispheric lateralization.

OBJECTIVE: To evaluate whether a simple auditory paradigm could demonstrate a difference in cortical lateralization between right- and left-handed subjects. Such information would be important for later development of clinical noninvasive tests of hemispheric language dominance in candidates for brain surgery. METHODS: Healthy subjects (10 strongly right-handed, 10 strongly left-handed, 5 weakly right-handed, and two ambidextrous) listened to binaural pairs of tones and pairs of Finnish vowels and decided whether the items in the pair were the same (target probability 20%). Cortical responses were recorded with whole-scalp magnetoencephalography. RESULTS: The laterality index for strengths of the auditory-cortex 100 ms responses (N100m) to vowels vs. tones suggested left-hemispheric dominance in 8 of the 10 strongly right-handed subjects, and right-hemispheric dominance in 7 of the 10 left-handed subjects. CONCLUSIONS: Our results demonstrate difference in hemispheric dominance for processing of vowels between right-handed and left-handed subjects. This difference resembles language lateralization suggested by previous invasive studies as well as by anatomical and functional comparisons in left- and right-handed subjects. SIGNIFICANCE: After comparison with the Wada test, this simple paradigm could prove useful as a noninvasive test for language lateralization in clinical settings.

Neuromagnetic localization of rhythmic activity in the human brain: a comparison of three methods.

Cortical rhythmic activity is increasingly employed for characterizing human brain function. Using MEG, it is possible to localize the generators of these rhythms. Traditionally, the source locations have been estimated using sequential dipole modeling. Recently, two new methods for localizing rhythmic activity have been developed, Dynamic Imaging of Coherent Sources (DICS) and Frequency-Domain Minimum Current Estimation (MCE(FD)). With new analysis methods emerging, the researcher faces the problem of choosing an appropriate strategy. The aim of this study was to compare the performance and reliability of these three methods. The evaluation was performed using measured data from four healthy subjects, as well as with simulations of rhythmic activity. We found that the methods gave comparable results, and that all three approaches localized the principal sources of oscillatory activity very well. Dipole modeling is a very powerful tool once appropriate subsets of sensors have been selected. MCE(FD) provides simultaneous localization of sources and was found to give a good overview of the data. With DICS, it was possible to separate close-by sources that were not retrieved by the other two methods.

Neural correlates of letter-string length and lexicality during reading in a regular orthography.

Behavioral studies have shown that short letter strings are read faster than long letter-strings and words are read faster than nonwords. Here, we describe the dynamics of letter-string length and lexicality effects at the cortical level, using magnetoencephalography, during a reading task in Finnish with long (eight-letter) and short (four-letter) word/nonword stimuli. Length effects were observed in two spatially and temporally distinct cortical activations: (1) in the occipital cortex at about 100 msec by the strength of activation, regardless of the lexical status of the stimuli, and (2) in the left superior temporal cortex between 200 and 600 msec by the duration of activation, with words showing a smaller effect than nonwords. A significant lexicality effect was also evident in this later activation, with stronger activation and longer duration for nonwords than words. There seem to be no distinct cortical areas for reading words and nonwords. The early length effect is likely to be due to the low-level visual analysis common to all stimulus letter-strings. The later lexicality and length effects apparently reflect converging lexico-semantic and phonological influences, and are discussed in terms of dual-route and single-route connectionist models of reading.

The 3D topography of MEG source localization accuracy: effects of conductor model and noise.

OBJECTIVE: To evaluate the effect that different head conductor models have on the source estimation accuracy of magnetoencephalography (MEG) under realistic conditions. METHODS: Magnetic fields evoked by current dipoles were simulated using a highly refined 3-layer realistically shaped conductor model. Noise from a real MEG measurement was added to the simulated fields. Source parameters (location, strength, orientation) were estimated from the noisy signals using 3 spherically symmetric models and several one- and 3-layer realistically shaped boundary-element models. The effect of different measurement sensors (gradiometers, magnetometers) was also tested. RESULTS: The noise typically present in brain signals masked the errors due to the different conductor models so that in most situations the models gave comparable results. Active cortical areas around the vertex and in the temporal, frontoparietal, and occipital regions were typically found with 2-4 mm accuracy, whereas source localization in several anterior frontal lobe and deep brain structures yielded errors exceeding 2 cm. Localization in anterior frontal regions may benefit most from the use of realistically shaped models. CONCLUSIONS: The traditionally used sphere model is an adequate model for most research purposes. Any means that increase the signal-to-noise ratio are of highest importance in attempting to improve the source estimation accuracy.

Properties of MEG tomographic maps obtained with spatial filtering.

Magnetoencephalography (MEG) has, in comparison with other functional imaging modalities, unique properties which makes it the prime candidate for the noninvasive investigation of long-range oscillatory interactions in the human brain. Recent methodological developments based on spatial filtering introduced the computation of functional tomographic maps covering the entire brain and representing the distribution of coherence to a given reference signal or the distribution of power. Because of the spatially inhomogeneous sensitivity profile of the MEG sensors, the spatial resolution of the resulting functional maps is not isotropic across the brain. Here, we introduce a convenient analytic expression for the computation of the spatial resolution at any given point in the brain. We derive the dependence of the resolution on the signal-to-noise ratio and on the changes of the leadfields. The resolution map can be displayed on anatomical MRI in the same way as the functional maps. In addition, we establish a procedure for computing a confidence volume of local maxima which is based on a bootstrap method. The confidence volume is a measure for the uncertainty of the localization. It is important for assigning local maxima of activation to specific anatomical structures and may be used to test for differences in localization between different experimental conditions.

Category-specific occipitotemporal activation during face perception in dyslexic individuals: an MEG study.

In dyslexia, it is consistently found that letter strings produce an abnormally weak or no response in the left occipitotemporal cortex. Time-sensitive imaging techniques have located this deficit to the category-specific processing stage at about 150 ms after stimulus presentation. The typically reported behavioral impairments in dyslexia suggest that the lack of occipitotemporal activation is specific to reading. It could, however, also reflect a more general dysfunction in the left inferior occipitotemporal cortex or in the time window of category-specific activation (150 to 200 ms). As early cortical processing of faces follows a sequence practically identical to that for letter strings, both in location and in timing, we investigated these possibilities by comparing face-specific occipitotemporal activations in dyslexic and non-reading-impaired subjects. We found that both the stage of general visual feature analysis at about 100 ms and the earliest face-specific activation at about 150 ms were essentially normal in the dyslexic individuals. The present results emphasize the special nature of the occipitotemporal abnormality to letter strings in dyslexia. However, in behavioral tests dyslexic subjects were slower and more error-prone than non-reading-impaired subjects in judging the similarity of faces and geometrical shapes. This effect may be related to reduced activation of the right parietotemporal cortex at about 250 ms after stimulus onset.

Infant-mother interaction as a predictor of child's chronic health problems.

BACKGROUND: Psychological stress is associated with physical illnesses like asthma or infections. For an infant, situations perceived as stressful are highly dependent on the relationship with the caregiver. Constantly poor mother-infant interaction increases the child's vulnerability to stressful conditions and experiences. The aim of the study was to investigate the impact of the quality of early mother-infant interaction on the subsequent physical health of the child. Poor mother-infant interaction was hypothesized to be associated with chronic or recurrent health problems in the child. PARTICIPANTS: Fifty-seven mother-infant dyads from families at risk of psychosocial problems and 63 from non-risk families, altogether 120 dyads, participated in the study. Families were drawn from normal population, from well-baby clinics in the city of Tampere, Finland. Infants were full-term and healthy, families with severe risks like psychotic illnesses of the parents or a history of child protection concerns were excluded from the study. METHODS: After the initial interview with the mother, the mother-infant interaction was videotaped when the infants were 8-11 weeks of age and the interaction was assessed using the Global Rating Scale for Mother-Infant Interaction (Murray et al. 1996a). After the 2-year follow-up mothers were interviewed again and the health problems of the child were elicited. RESULTS: Poor dyadic mother-infant interaction and infant's poor interactive behaviour assessed at two months were separately associated with the physical health of the child during the two-year follow-up. After adjusting for other factors in the logistic regression analysis infant's poor interactive behaviour remained as a significant predictor of chronic or recurrent health problems in the child. Infant's health problems at the time of the initial interview and day care centre attendance were also significant predictors. CONCLUSIONS: The results suggest that interactional issues between a mother and her infant are related to the child's subsequent physical health. Children with recurrent or chronic health problems may have relationship difficulties with which they need help. Also, early avoidant behaviour of the infant should be regarded as an indicator of the infant's distress with possibly adverse outcomes in the child's physical health, among other consequences.

Dynamics of visual feature analysis and object-level processing in face versus letter-string perception.

Neurones in the human inferior occipitotemporal cortex respond to specific categories of images, such as numbers, letters and faces, within 150-200 ms. Here we identify the locus in time when stimulus-specific analysis emerges by comparing the dynamics of face and letter-string perception in the same 10 individuals. An ideal paradigm was provided by our previous study on letter-strings, in which noise-masking of stimuli revealed putative visual feature processing at 100 ms around the occipital midline followed by letter-string-specific activation at 150 ms in the left inferior occipitotemporal cortex. In the present study, noise-masking of cartoon-like faces revealed that the response at 100 ms increased linearly with the visual complexity of the images, a result that was similar for faces and letter-strings. By 150 ms, faces and letter-strings had entered their own stimulus-specific processing routes in the inferior occipitotemporal cortex, with identical timing and large spatial overlap. However, letter-string analysis lateralized to the left hemisphere, whereas face processing occurred more bilaterally or with right-hemisphere preponderance. The inferior occipitotemporal activations at approximately 150 ms, which take place after the visual feature analysis at approximately 100 ms, are likely to represent a general object-level analysis stage that acts as a rapid gateway to higher cognitive processing.

The neural basis of intermittent motor control in humans.

The basic question of whether the human brain controls continuous movements intermittently is still under debate. Here we show that 6- to 9-Hz pulsatile velocity changes of slow finger movements are directly correlated to oscillatory activity in the motor cortex, which is sustained by cerebellar drive through thalamus and premotor cortex. Our findings suggest that coupling of 6- to 9-Hz oscillatory activity in the cerebello-thalamo-cortical loop represents the neural mechanism for the intermittent control of continuous movements.

The pure-tone hearing thresholds of otologically healthy 14-year-old children.

The mean pure-tone air conduction (AC) and bone conduction (BC) hearing thresholds (HT) of 534 randomly selected, caucasian, white, urban children with normal otoscopy, otomicroscopy and impedance audiometry, i.e. normal middle ear function, are presented here. Children with pathological middle ear findings or abnormal impedance audiometry were excluded. The average age was 13.8 years, SD 0.5, at the date of examination. The mean air conduction thresholds varied between 0.6 dB at 1 kHz and 9.9 dB at 6 kHz, and the bone conduction thresholds varied between -1.1 dB at 0.5 kHz and 1.1 dB at 4 kHz. The pure-tone average (PTA) (the average of AC hearing thresholds of 0.5, 1 and 2 kHz) of all ears was 1.5 dB. Ninety to ninety-eight per cent of pure-tone AC hearing thresholds at frequencies of 0.5-4 kHz were between -5 dB and 10 dB. The distributions are presented and compared.

Relation between frontal 3-7 Hz MEG activity and the efficacy of ECT in major depression.

The efficacy of electroconvulsive therapy (ECT) in major depression has been linked to the accentuation of postconvulsive prefrontal electroencephalography slow-wave activity. We investigated the change in slow-wave activity (0.5-7 Hz) using whole-scalp magnetoencephalographic (MEG) recordings. The 3-7 Hz (theta) activity increased in the right frontal and occipital regions during the course of treatment. After four treatments, the increase of the theta activity in the left frontal cortex correlated with the efficacy of the ECT treatment. Moreover, the change of the ratio of left and right frontal theta activity to occipital theta activity had a positive correlation with the therapeutic effect. These findings suggest that an efficient ECT treatment increases MEG theta activity in the frontal cortex.