Evidence for genetic regulation of the human parieto-occipital 10-Hz rhythmic activity.

Several functional and morphological brain measures are partly under genetic control. The identification of direct links between neuroimaging signals and corresponding genetic factors can reveal cellular-level mechanisms behind the measured macroscopic signals and contribute to the use of imaging signals as probes of genetic function. To uncover possible genetic determinants of the most prominent brain signal oscillation, the parieto-occipital 10-Hz alpha rhythm, we measured spontaneous brain activity with magnetoencephalography in 210 healthy siblings while the subjects were resting, with eyes closed and open. The reactivity of the alpha rhythm was quantified from the difference spectra between the two conditions. We focused on three measures: peak frequency, peak amplitude and the width of the main spectral peak. In accordance with earlier electroencephalography studies, spectral peak amplitude was highly heritable (h(2)  > 0.75). Variance component-based analysis of 28 000 single-nucleotide polymorphism markers revealed linkage for both the width and the amplitude of the spectral peak. The strongest linkage was detected for the width of the spectral peak over the left parieto-occipital cortex on chromosome 10 (LOD = 2.814, nominal P < 0.03). This genomic region contains several functionally plausible genes, including GRID1 and ATAD1 that regulate glutamate receptor channels mediating synaptic transmission, NRG3 with functions in brain development and HRT7 involved in the serotonergic system and circadian rhythm. Our data suggest that the alpha oscillation is in part genetically regulated, and that it may be possible to identify its regulators by genetic analyses on a realistically modest number of samples.

Genome-wide linkage analysis of human auditory cortical activation suggests distinct loci on chromosomes 2, 3, and 8.

Neural processes are explored through macroscopic neuroimaging and microscopic molecular measures, but the two levels remain primarily detached. The identification of direct links between the levels would facilitate use of imaging signals as probes of genetic function and, vice versa, access to molecular correlates of imaging measures. Neuroimaging patterns have been mapped for a few isolated genes, chosen based on their connection with a clinical disorder. Here we propose an approach that allows an unrestricted discovery of the genetic basis of a neuroimaging phenotype in the normal human brain. The essential components are a subject population that is composed of relatives and selection of a neuroimaging phenotype that is reproducible within an individual and similar between relatives but markedly variable across a population. Our present combined magnetoencephalography and genome-wide linkage study in 212 healthy siblings demonstrates that auditory cortical activation strength is highly heritable and, specifically in the right hemisphere, regulated oligogenically with linkages to chromosomes 2q37, 3p12, and 8q24. The identified regions delimit as candidate genes TRAPPC9, operating in neuronal differentiation, and ROBO1, regulating projections of thalamocortical axons. Identification of normal genetic variation underlying neurophysiological phenotypes offers a non-invasive platform for an in-depth, concerted capitalization of molecular and neuroimaging levels in exploring neural function.

Parametric merging of MEG and fMRI reveals spatiotemporal differences in cortical processing of spoken words and environmental sounds in background noise.

There is an increasing interest to integrate electrophysiological and hemodynamic measures for characterizing spatial and temporal aspects of cortical processing. However, an informative combination of responses that have markedly different sensitivities to the underlying neural activity is not straightforward, especially in complex cognitive tasks. Here, we used parametric stimulus manipulation in magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) recordings on the same subjects, to study effects of noise on processing of spoken words and environmental sounds. The added noise influenced MEG response strengths in the bilateral supratemporal auditory cortex, at different times for the different stimulus types. Specifically for spoken words, the effect of noise on the electrophysiological response was remarkably nonlinear. Therefore, we used the single-subject MEG responses to construct parametrization for fMRI data analysis and obtained notably higher sensitivity than with conventional stimulus-based parametrization. fMRI results showed that partly different temporal areas were involved in noise-sensitive processing of words and environmental sounds. These results indicate that cortical processing of sounds in background noise is stimulus specific in both timing and location and provide a new functionally meaningful platform for combining information obtained with electrophysiological and hemodynamic measures of brain function.

Modulation of brain activity after learning predicts long-term memory for words.

The acquisition and maintenance of new language information, such as picking up new words, is a critical human ability that is needed throughout the life span. Most likely you learned the word "blog" quite recently as an adult, whereas the word "kipe," which in the 1970s denoted stealing, now seems unfamiliar. Brain mechanisms underlying the long-term maintenance of new words have remained unknown, albeit they could provide important clues to the considerable individual differences in the ability to remember words. After successful training of a set of novel object names we tracked, over a period of 10 months, the maintenance of this new vocabulary in 10 human participants by repeated behavioral tests and magnetoencephalography measurements of overt picture naming. When naming-related activation in the left frontal and temporal cortex was enhanced 1 week after training, compared with the level at the end of training, the individual retained a good command of the new vocabulary at 10 months; vice versa, individuals with reduced activation at 1 week posttraining were less successful in recalling the names at 10 months. This finding suggests an individual neural marker for memory, in the context of language. Learning is not over when the acquisition phase has been successfully completed: neural events during the access to recently established word representations appear to be important for the long-term outcome of learning.

Accessing newly learned names and meanings in the native language.

Ten healthy adults encountered pictures of unfamiliar archaic tools and successfully learned either their name, verbal definition of their usage, or both. Neural representation of the newly acquired information was probed with magnetoencephalography in an overt picture-naming task before and after learning, and in two categorization tasks after learning. Within 400 ms, activation proceeded from occipital through parietal to left temporal cortex, inferior frontal cortex (naming) and right temporal cortex (categorization). Comparison of naming of newly learned versus familiar pictures indicated that acquisition and maintenance of word forms are supported by the same neural network. Explicit access to newly learned phonology when such information was known strongly enhanced left temporal activation. By contrast, access to newly learned semantics had no comparable, direct neural effects. Both the behavioral learning pattern and neurophysiological results point to fundamentally different implementation of and access to phonological versus semantic features in processing pictured objects.

Cortical dynamics of visual/semantic vs. phonological analysis in picture confrontation.

Picture naming covers the main stages of word production from concept retrieval to articulation. Cortical correlates of picture naming have been characterized with both haemodynamic and neurophysiological methods but the association of specific activation patterns with the hypothesized processing stages remains elusive. Here we used categorization tasks to selectively highlight different components of picture confrontation, from visual analysis (VIS) to semantic (SEM) and phonological access (PHON), and compared these time courses of activation with that obtained during picture naming (NAM). Brain activity was recorded with whole-head magnetoencephalography (MEG). Following the initially similar activation patterns in occipital and parietal areas, task effects (stronger activation in NAM/PHON than in SEM/VIS) emerged after 300 ms, in the sustained activation of the left posterior temporal and bilateral inferior frontal cortex, apparently reflecting enhancement of phonological and phonetic/articulatory processing.

Activation of the human sensorimotor cortex during error-related processing: a magnetoencephalography study.

We studied error-related processing using magnetoencephalography (MEG). Previous event-related potential studies have documented error negativity or error-related negativity after incorrect responses, with a suggested source in the anterior cingulate cortex or supplementary motor area. We compared activation elicited by correct and incorrect trials using auditory and visual choice-reaction time tasks. Source areas showing different activation patterns in correct and error conditions were mainly located in sensorimotor areas, both ipsi- and contralateral to the response, suggesting that activation of sensorimotor circuits accompanies error processing. Additional activation at various other locations suggests a distributed network of brain regions active during error-related processing. Activation specific to incorrect trials tended to occur later in MEG than EEG data, possibly indicating that EEG and MEG detect different neural networks involved in error-related processes.

Hemispheric balance in processing attended and non-attended vowels and complex tones.

We compared cortical processing of attended and non-attended vowels and complex tones, using a whole-head neuromagnetometer, to test for possible hemispheric differences. Stimuli included vowels [a] and [i], spoken by two female Finnish speakers, and two complex tones, each with two pure tone components corresponding to the first and second formant frequencies (F1-F2) of the vowels spoken by speaker 1. Sequences including both vowels and complex tones were presented to eight Finnish males during passive and active (phoneme/speaker/complex tone identification) listening. Sequences including only vowels were presented to five of the subjects during passive listening and during a phoneme identification task. The vowel [i] spoken by speaker 1 and the corresponding complex tone were frequent, non-target stimuli. Responses evoked by these frequent stimuli were analyzed. Cortical activation at approximately 100 ms was stronger for the complex tone than the vowel in the right hemisphere (RH). Responses were similar during active and passive listening. Hemispheric balance remained the same when the vowel was presented in sequences including only vowels. The reduction of RH activation for vowels as compared with complex tones indicates a relative increase of left hemisphere involvement, possibly reflecting a shift towards more language-specific processing.

Topography of the auditory evoked potential in humans reflects differences between vowels embedded in pseudo-words.

To study the processing of vowels embedded in more complex linguistic structures, we compared cortical responses for pseudo-words. Auditory evoked potentials were recorded in 11 right-handed females using a passive oddball paradigm, with /pemu/ and /pomu/ as standard stimuli, differing only with respect to the first syllable. Topographic differences in the N100 were observed between the standards: /pemu/ had larger amplitudes than /pomu/ at more posterior electrode sites whereas a reverse pattern was found at more anterior positions along the midline. This topographic difference can be explained by different generators for the two stimuli. Different vowels and/or the initial formant transition possibly activate different neural populations in the auditory cortex, also when the vowels are embedded in pseudo-words.

Auditory cortical activation in Finnish and Swedish speaking Finns: a magnetoencephalographic study.

To study the effects of linguistic background on auditory processing, magnetoencephalographic responses for pure tones (120 Hz, 1 and 4 kHz), [u] and a complex tone (with three pure tone components corresponding to the three lowest formant frequencies of [u]) were recorded in ten Finnish and ten Swedish speaking Finnish males. Auditory cortical activation, maximal at about 100 ms after stimulus onset, was stronger in the right hemisphere (RH) for all stimuli. At 175-225 ms, Swedish speaking subjects had larger inter-hemispheric differences and different signal morphology in the RH than Finnish speaking subjects, suggesting that linguistic background influences basic auditory processes. Possibly, Swedish speaking subjects had retained a juvenile response component due to their bilingual surrounding after early childhood.