Rapid Cortical Plasticity Induced by Active Associative Learning of Novel Words in Human Adults.

Human speech requires that new words are routinely memorized, yet neurocognitive mechanisms of such acquisition of memory remain highly debatable. Major controversy concerns the question whether cortical plasticity related to word learning occurs in neocortical speech-related areas immediately after learning, or neocortical plasticity emerges only on the second day after a prolonged time required for consolidation after learning. The functional spatiotemporal pattern of cortical activity related to such learning also remains largely unknown. In order to address these questions, we examined magnetoencephalographic responses elicited in the cerebral cortex by passive presentations of eight novel pseudowords before and immediately after an operant conditioning task. This associative procedure forced participants to perform an active search for unique meaning of four pseudowords that referred to movements of left and right hands and feet. The other four pseudowords did not require any movement and thus were not associated with any meaning. Familiarization with novel pseudowords led to a bilateral repetition suppression of cortical responses to them; the effect started before or around the uniqueness point and lasted for more than 500 ms. After learning, response amplitude to pseudowords that acquired meaning was greater compared with response amplitude to pseudowords that were not assigned meaning; the effect was significant within 144-362 ms after the uniqueness point, and it was found only in the left hemisphere. Within this time interval, a learning-related selective response initially emerged in cortical areas surrounding the Sylvian fissure: anterior superior temporal sulcus, ventral premotor cortex, the anterior part of intraparietal sulcus and insula. Later within this interval, activation additionally spread to more anterior higher-tier brain regions, and reached the left temporal pole and the triangular part of the left inferior frontal gyrus extending to its orbital part. Altogether, current findings evidence rapid plastic changes in cortical representations of meaningful auditory word-forms occurring almost immediately after learning. Additionally, our results suggest that familiarization resulting from stimulus repetition and semantic acquisition resulting from an active learning procedure have separable effects on cortical activity.

Effortful verb retrieval from semantic memory drives beta suppression in mesial frontal regions involved in action initiation.

The contribution of the motor cortex to the semantic retrieval of verbs remains a subject of debate in neuroscience. Here, we examined whether additional engagement of the cortical motor system was required when access to verbs semantics was hindered during a verb generation task. We asked participants to produce verbs related to presented noun cues that were either strongly associated with a single verb to prompt fast and effortless verb retrieval, or were weakly associated with multiple verbs and more difficult to respond to. Using power suppression of magnetoencephalography beta oscillations (15-30 Hz) as an index of cortical activation, we performed a whole-brain analysis in order to identify the cortical regions sensitive to the difficulty of verb semantic retrieval. Highly reliable suppression of beta oscillations occurred 250 ms after the noun cue presentation and was sustained until the onset of verbal response. This was localized to multiple cortical regions, mainly in the temporal and frontal lobes of the left hemisphere. Crucially, the only cortical regions where beta suppression was sensitive to the task difficulty, were the higher order motor areas on the medial and lateral surfaces of the frontal lobe. Stronger activation of the premotor cortex and supplementary motor area accompanied the effortful verb retrieval and preceded the preparation of verbal responses for more than 500 ms, thus, overlapping with the time window of verb retrieval from semantic memory. Our results suggest that reactivation of verb-related motor plans in higher order motor circuitry promotes the semantic retrieval of target verbs.

Simultaneous Processing of Noun Cue and to-be-Produced Verb in Verb Generation Task: Electromagnetic Evidence.

A long-standing but implicit assumption is that words strongly associated with a presented cue are automatically activated in the memory through rapid spread of activation within brain semantic networks. The current study was aimed to provide direct evidence of such rapid access to words' semantic representations and to investigate its neural sources using magnetoencephalography (MEG) and distributed source localization technique. Thirty-three neurotypical subjects underwent the MEG recording during verb generation task, which was to produce verbs related to the presented noun cues. Brain responses evoked by the noun cues were examined while manipulating the strength of association between the noun and the potential verb responses. The strong vs. weak noun-verb association led to a greater noun-related neural response at 250-400 ms after cue onset, and faster verb production. The cortical sources of the differential response were localized in left temporal pole, previously implicated in semantic access, and left ventrolateral prefrontal cortex (VLPFC), thought to subserve controlled semantic retrieval. The strength of the left VLPFC's response to the nouns with strong verb associates was positively correlated to the speed of verbs production. Our findings empirically validate the theoretical expectation that in case of a strongly connected noun-verb pair, successful access to target verb representation may occur already at the stage of lexico-semantic analysis of the presented noun. Moreover, the MEG results suggest that contrary to the previous conclusion derived from fMRI studies left VLPFC supports selection of the target verb representations, even if they were retrieved from semantic memory rapidly and effortlessly. The discordance between MEG and fMRI findings in verb generation task may stem from different modes of neural activation captured by phase-locked activity in MEG and slow changes of blood-oxygen-level-dependent (BOLD) signal in fMRI.

Altered modulation of gamma oscillation frequency by speed of visual motion in children with autism spectrum disorders.

BACKGROUND: Recent studies link autism spectrum disorders (ASD) with an altered balance between excitation and inhibition (E/I balance) in cortical networks. The brain oscillations in high gamma-band (50-120 Hz) are sensitive to the E/I balance and may appear useful biomarkers of certain ASD subtypes. The frequency of gamma oscillations is mediated by level of excitation of the fast-spiking inhibitory basket cells recruited by increasing strength of excitatory input. Therefore, the experimental manipulations affecting gamma frequency may throw light on inhibitory networks dysfunction in ASD. METHODS: Here, we used magnetoencephalography (MEG) to investigate modulation of visual gamma oscillation frequency by speed of drifting annular gratings (1.2, 3.6, 6.0 °/s) in 21 boys with ASD and 26 typically developing boys aged 7-15 years. Multitaper method was used for analysis of spectra of gamma power change upon stimulus presentation and permutation test was applied for statistical comparisons. We also assessed in our participants visual orientation discrimination thresholds, which are thought to depend on excitability of inhibitory networks in the visual cortex. RESULTS: Although frequency of the oscillatory gamma response increased with increasing velocity of visual motion in both groups of participants, the velocity effect was reduced in a substantial proportion of children with ASD. The range of velocity-related gamma frequency modulation correlated inversely with the ability to discriminate oblique line orientation in the ASD group, while no such correlation has been observed in the group of typically developing participants. CONCLUSIONS: Our findings suggest that abnormal velocity-related gamma frequency modulation in ASD may constitute a potential biomarker for reduced excitability of fast-spiking inhibitory neurons in a subset of children with ASD.

Frequency of gamma oscillations in humans is modulated by velocity of visual motion.

Gamma oscillations are generated in networks of inhibitory fast-spiking (FS) parvalbumin-positive (PV) interneurons and pyramidal cells. In animals, gamma frequency is modulated by the velocity of visual motion; the effect of velocity has not been evaluated in humans. In this work, we have studied velocity-related modulations of gamma frequency in children using MEG/EEG. We also investigated whether such modulations predict the prominence of the "spatial suppression" effect (Tadin D, Lappin JS, Gilroy LA, Blake R. Nature 424: 312-315, 2003) that is thought to depend on cortical center-surround inhibitory mechanisms. MEG/EEG was recorded in 27 normal boys aged 8-15 yr while they watched high-contrast black-and-white annular gratings drifting with velocities of 1.2, 3.6, and 6.0°/s and performed a simple detection task. The spatial suppression effect was assessed in a separate psychophysical experiment. MEG gamma oscillation frequency increased while power decreased with increasing velocity of visual motion. In EEG, the effects were less reliable. The frequencies of the velocity-specific gamma peaks were 64.9, 74.8, and 87.1 Hz for the slow, medium, and fast motions, respectively. The frequency of the gamma response elicited during slow and medium velocity of visual motion decreased with subject age, whereas the range of gamma frequency modulation by velocity increased with age. The frequency modulation range predicted spatial suppression even after controlling for the effect of age. We suggest that the modulation of the MEG gamma frequency by velocity of visual motion reflects excitability of cortical inhibitory circuits and can be used to investigate their normal and pathological development in the human brain.

Auditory magnetic response to clicks in children and adults: its components, hemispheric lateralization and repetition suppression effect.

The auditory magnetic event-related fields (ERF) qualitatively change through the child development, reflecting maturation of auditory cortical areas. Clicks presented with long inter-stimulus interval produce distinct ERF components, and may appear useful to characterize immature EFR morphology in children. The present study is aimed to investigate morphology of the auditory ERFs in school-age children, as well as lateralization and repetition suppression of ERF components evoked by the clicks. School-age children and adults passively listened to pairs of click presented to the right ear, left ear or binaurally, with 8-11 s intervals between the pairs and a 1 s interval within a pair. Adults demonstrated a typical P50m/N100m response. Unlike adults, children had two distinct components preceding the N100m-P50m (at ~65 ms) and P100m (at ~100 ms). The P100m dominated the child ERF, and was most prominent in response to binaural stimulation. The N100m in children was less developed than in adults and partly overlapped in time with the P100m, especially in response to monaural clicks. Strong repetition suppression was observed for P50m both in children and adults, P100m in children and N100m in adults. Both children and adults demonstrated ERF amplitude and/or latency right hemispheric advantage effects that may reflect right hemisphere dominance for preattentive arousal processes. Our results contribute to the knowledge concerning development of auditory processing and its lateralization in children and have implications for investigation of the auditory evoked fields in developmental disorders.

Auditory cortex responses to clicks and sensory modulation difficulties in children with autism spectrum disorders (ASD).

Auditory sensory modulation difficulties are common in autism spectrum disorders (ASD) and may stem from a faulty arousal system that compromises the ability to regulate an optimal response. To study neurophysiological correlates of the sensory modulation difficulties, we recorded magnetic field responses to clicks in 14 ASD and 15 typically developing (TD) children. We further analyzed the P100m, which is the most prominent component of the auditory magnetic field response in children and may reflect preattentive arousal processes. The P100m was rightward lateralized in the TD, but not in the ASD children, who showed a tendency toward P100m reduction in the right hemisphere (RH). The atypical P100m lateralization in the ASD subjects was associated with greater severity of sensory abnormalities assessed by Short Sensory Profile, as well as with auditory hypersensitivity during the first two years of life. The absence of right-hemispheric predominance of the P100m and a tendency for its right-hemispheric reduction in the ASD children suggests disturbance of the RH ascending reticular brainstem pathways and/or their thalamic and cortical projections, which in turn may contribute to abnormal arousal and attention. The correlation of sensory abnormalities with atypical, more leftward, P100m lateralization suggests that reduced preattentive processing in the right hemisphere and/or its shift to the left hemisphere may contribute to abnormal sensory behavior in ASD.