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.

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.

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.

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.

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.

Human cortical oscillations: a neuromagnetic view through the skull.

The mammalian cerebral cortex generates a variety of rhythmic oscillations, detectable directly from the cortex or the scalp. Recent non-invasive recordings from intact humans, by means of neuromagnetometers with large sensor arrays, have shown that several regions of the healthy human cortex have their own intrinsic rhythms, typically 8-40 Hz in frequency, with modality- and frequency-specific reactivity. The conventional hypotheses about the functional significance of brain rhythms extend from epiphenomena to perceptual binding and object segmentation. Recent data indicate that some cortical rhythms can be related to periodic activity of peripheral sensor and effector organs.

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.

Spatiotemporal characteristics of sensorimotor neuromagnetic rhythms related to thumb movement.

To assess the spatial extent and temporal behavior of rolandic rhythms we recorded neuromagnetic signals from four healthy subjects with a 24-channel magnetometer. The subjects performed self-paced thumb movements or the motions were triggered by electrical stimulation of the median nerve at the wrist. The main frequency components of the magnetic mu rhythm signals centered at 10 and 20 Hz. Both components were completely suppressed during the movement and increased substantially 0.5-2.5 s after it; the 20-Hz component reacted about 300 ms faster. The rebound was stronger after self-paced than after stimulated motion, and after contra- than after ipsilateral movement. The reactive source areas were identified for both frequency ranges, and they clustered on partly overlapping cortical areas of 6-8 cm2 wide along the course of the central sulcus. The 10-Hz rhythmic oscillations occurred predominantly at the primary somatosensory hand cortex; the sources of the 20-Hz signals were slightly more anterior. We hypothesize that the 10-Hz signal is a true somatosensory rhythm whereas the 20-Hz activity is essentially somatomotor in origin.

Left-hemisphere dominance for processing of vowels: a whole-scalp neuromagnetic study.

Brain activation of 11 healthy right-handed subjects was studied with magnetoencephalography to estimate individual hemispheric dominance for speech sounds. The auditory stimuli comprised binaurally presented Finnish vowels, tones, and piano notes in groups of two or four stimuli. The subjects were required to detect whether the first and the last item in a group were the same. In the left hemisphere, vowels evoked significantly stronger (37-79%) responses than notes and tones, whereas in the right hemisphere the responses to different stimuli did not differ significantly. Specifically, in the two-stimulus task, all 11 subjects showed left-hemisphere dominance in the vowel vs tone comparison. This simple paradigm may be helpful in non-invasive evaluation of language lateralization.

Functional organization of the auditory cortex is different in stutterers and fluent speakers.

Impaired auditory feedback has been suggested to cause stuttering, and subtle irregularities of audition have been reported in behavioural studies. To characterize processing at the auditory cortical level, we recorded neuromagnetic responses to monaural tones in nine stutterers and 10 fluent speakers while the subjects were reading silently, with mouth movements only, aloud, and in chorus with another person. The basic functional organization of the auditory cortices was found to be different in stutterers and controls. The altered interhemispheric balance in stutterers was affected by speech production, due to changes in the left auditory cortical representation, and more severely by self-paced than accompanied speech. This may lead to transient non-optimal interpretation of the auditory input and affect speech fluency.

Longitudinal study of maternal depressive symptoms and child well-being.

OBJECTIVE: To investigate whether prenatal, postnatal, and/or current maternal depressive symptoms are associated with low level of psychosocial functioning or high level of emotional/behavioral problems in school-age children. METHOD: As part of a prospective longitudinal study, maternal depressive symptoms were screened with the Edinburgh Postnatal Depression Scale prenatally, postnatally, and when the children were 8 to 9 years old. The original sample of 349 mothers was collected in 1989-1990 in Tampere, Finland. Of the 270 mother-child pairs at the latest stage of the study in 1997-1998, 188 mother-child pairs participated and 147 were included. The associations between maternal depressive symptoms at different points in time and the level of children's psychosocial functioning and problems reported on the Child Behavior Checklist and Teacher's Report Form were examined. RESULTS: Children's low social competence and low adaptive functioning were associated with concurrent maternal depressive symptoms. Maternal postnatal depressive symptoms predicted low social competence. The presence of prenatal depressive symptoms in the mother was a strong predictor of child's high externalizing and total problem levels (odds ratio 3.1, 95% confidence interval 1.1-8.9 and odds ratio 8.5, 95% confidence interval 2.7-26.5). Prenatal as well as recurrent maternal depressive symptoms were associated with the least favorable child outcome. CONCLUSIONS: Maternal depressive symptomatology at any time, especially prenatally, is a risk factor for the child's well-being. This should be noted already in prenatal care. The timing and the recurrence of maternal depressive symptoms affect the outcome for the child.

Suppression of magnetic mu rhythm during parkinsonian tremor.

We recorded spontaneous magnetoencephalographic (MEG) activity and somatosensory-evoked fields (SEFs) with a 24-channel planar SQUIDgradiometer in five patients with hemiparkinsonism. The SEFs of the patients were within normal limits. During tremorless periods, the spontaneous activity over the somatomotor cortex had a frequency peak at approximately 10 Hz in all five patients and another at approximately 20 Hz in three. Tremor dampened the 10-Hz activity in all patients; in three the effect was bilateral. Tremor did not increase MEG activity at the tremor frequency. The suppression of the mu rhythm by the parkinsonian tremor resembled that occurring during voluntary movements in healthy subjects.

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.

Subject's own speech reduces reactivity of the human auditory cortex.

Previous studies on monkeys have shown that uttering-related cortical areas exert an inhibitory effect on the auditory cortex, and cerebral blood-flow analyses on humans have revealed modulation of the activity of the auditory cortex during own speech. To study this modulation on a millisecond time scale, we recorded neuromagnetic evoked responses to short 1-kHz tones while the subjects were reading silently and aloud. The 100-ms response (M100) of the auditory cortex was delayed by 10-21 ms and its amplitude was dampened by 44-71% during reading aloud compared with reading silently. This effect was more prominent in responses to ipsilateral than contralateral tones, possibly due to a sum effect of diminished ipsilateral input to the cortex and decreased transcallosal excitation.

Evidence for reactive magnetic 10-Hz rhythm in the human auditory cortex.

We tested the hypothesis that neurons in the human auditory cortex show spontaneous oscillations around 10 Hz, and that this activity ('tau' rhythm) is affected by auditory input. Cortical activity was recorded with a 122-channel whole-scalp neuromagnetometer from healthy adults while they were presented with monaural 500-ms bursts of white noise. The reactivity of spontaneous oscillations was studied over the whole cortex using the Temporal Spectral Evolution method. Oscillatory 6.5-9.5 Hz activity, with sources in the superior temporal lobes, was transiently suppressed by the sounds in eight out of nine subjects. Our results support the existence of a distinct, reactive auditory rhythm in the human temporal cortex.

Tactile information from the human hand reaches the ipsilateral primary somatosensory cortex.

Neuromagnetic responses to median nerve stimulation were studied in six healthy right-handed subjects. In the rest condition, only the right and left median nerves were alternately stimulated at the wrists. In two other conditions, continuous superficial tactile stimulation was concurrently applied to either the left or right hand. Tactile stimulation of palm and fingers of one hand enhanced, in the ipsilateral primary somatosensory cortex (SI), responses to median nerve stimulation of the other hand. This effect was stronger in the left than the right SI. Our data provide evidence in humans for the access of cutaneous information from the hands to ipsilateral SI, probably via excitatory transcallosal pathways. This interhemispheric information transfer may represent a neurophysiological substrate of somatosensory fusion between the hands.

Human cortical 40 Hz rhythm is closely related to EMG rhythmicity.

We recorded cortical neuromagnetic rhythms during self-paced index-finger movements from a subject previously reported to show prominent 40 Hz electroencephalographic activity during motor behavior. The 10 and 20 Hz components of the rolandic mu rhythm were bilaterally suppressed, whereas the contralateral 40 Hz (35-41 Hz) activity was slightly enhanced before both fast and slow movements and strongly enhanced during slow movements. The 40 Hz rhythm originated mainly in the hand motor cortex and was clearly correlated with the rhythmicity of the electromyogram from the extensor muscles, with a systematic time lag. In this subject motor preparation, and especially control of finger movements, may thus be associated with enhanced cortical rhythms near 40 Hz. The coherence of these rhythms with muscular firing patterns likely reflects communication between the sensorimotor cortex and the motor units.

Odorants activate the human superior temporal sulcus.

The human olfactory pathways are well defined up to the level of the prepiriform cortex but the neocortical projections and their functional organization are still largely unknown. We recorded whole-scalp neuromagnetic signals to olfactory stimulation with boluses of phenylethyl alcohol, hydrogen sulphide, and vanillin. The main magnetic response peaked about 700 ms after the stimulus onset. The three odorants activated overlapping cortical areas around the superior temporal sulci of both hemispheres, revealing a neocortical area involved in olfactory processing.

Neurophysiology of fluent and impaired reading: a magnetoencephalographic approach.

This article reviews a series of magnetoencephalographic (MEG) experiments aimed at identifying cortical areas and time windows relevant or even critical for fluent reading. The approach was to compare single-word processing in fluent and dyslexic readers. The activations which differed between the two groups were then studied in more detail to determine their functional roles. In fluent reading, overall visual feature processing occurs about 100 milliseconds (ms) after seeing a word, in the posteromedial extrastriate cortex bilaterally. This activation does not differentiate between letters and symbols. The first reading-specific signal is detected about 150 ms after word onset, when the left inferior occipitotemporal cortex responds preferentially to letter strings. After 200 ms, the left superior temporal cortex, in particular, is engaged in semantic processing of single words and their integration with connected text. While visual feature processing seems to be within normal limits in dyslexic subjects, reading is disrupted during the first 200 ms after seeing a word, at the letter-string specific stage. The subsequent activations are weak and delayed as compared with those in fluent readers. Also presented is a case of deep dyslexia, where the same tools were used to demonstrate that reading comprehension was still subserved by the left hemisphere despite severe damage.

Evidence of sharp frequency tuning in the human auditory cortex.

The frequency tuning of the human auditory cortex was studied by masking 100-ms tones of 1 and 2 kHz by continuous white-noise maskers with frequency notches around the tone frequencies. The subjects ignored the stimuli and concentrated on a reading task. The neuronal activity elicited by the test tones in the auditory cortex was measured with a 24-channel neuromagnetometer. The masker affected the amplitude and latency of the neuromagnetic N100m response, peaking about at 100 ms after stimulus onset, in a systematic way: the wider the notch, the shorter was the latency and the larger the amplitude. The source location of N100m in the auditory cortex did not depend on the notch width. Auditory filters at 1 and 2 kHz were modelled by a single-parameter rounded-exponential [Roex(p)] filter, based on the amplitude changes of N100m. The filters revealed sharp tuning of the auditory cortex, resembling that obtained in psychoacoustical masking studies. The results demonstrate that frequency tuning of the neurons or neuron ensembles in the human auditory cortex can be studied completely noninvasively. Moreover, since the stimuli were ignored by the subjects, the filter shape is not affected by the criterion adopted by the subject in the discrimination task.