Gender-specific association of the angiotensin converting enzyme gene with Alzheimer's disease

We measured human evoked magnetic fields to binaural sounds with an interaural time delay as a cue for auditory localization. By analyzing the topography of auditory-evoked magnetic fields in the middle-latency, we demonstrated that particular cortical regions represent the direction of sound localization by their activity level. Upon presenting a binaural sound, the first representations were found in the middle frontal region as well as the superior temporal region of the right hemisphere approximately 19 ms after the stimulation, but their patterns differed. Other cortical regions including the prefrontal and parietal spatial areas were affected within roughly 60 ms. The results showed that the right hemisphere is dominant even in the preattentive stage of auditory spatial processing of sounds from different directions.     

Fast optical imaging of frontal cortex during active and passive oddball tasks

This study used the high spatial and temporal resolution of the event-related optical signal (EROS) to investigate the timing of neuronal activity in frontal cortex during auditory target detection and passive oddball tasks. Activation in right middle frontal gyrus (MFG) peaked approximately 350 ms following rare target tones. This corresponded closely to the latency of the simultaneously recorded electrical P3 component. In addition, we found activation in left lateral MFG peaking at approximately 130 ms following tone onset for conditions that may have required response inhibition. These results correspond with activation patterns observed in similar fMRI studies, but provide temporal tags for the activated locations. These data may help bridge the gap between electrophysiological and hemodynamic measures of target detection and contribute to our understanding of the spatiotemporal dynamics of brain activity during target processing.     

Spatiotemporal Analysis of ERP During Chinese Idiom Comprehension

The objective of the present study was to elucidate the neural underpinning of Chinese idiom comprehension with spatiotemporal patterns of ERP. Thirteen subjects were required to decide whether the last character of each viewed Chinese four-character idiom was correct or not. Fuzzy c-means algorithm based on shape similarity was applied to segmenting spatiotemporal patterns of ERP. Statistical parametric map of t-statistic (SPM(t)) was performed after realignment according to the referential frame provided by fuzzy clustering in order to overcome temporal mismatch. Within 540 ms post-stimulus onset, the spatiotemporal patterns of ERP under both conditions could be segmented into 7 stages optimally and both share the first four microstates with variant membership functions and durations. SPM(t) presented significant differences in multiple regions in 3 stages: (1) during 120-150 ms, the early right hemispheric negativities (ERHN) inboth frontal and temporoparietal areas were likely to reflect both initial syntactic processing and visual word-form mismatch; (2) during 320-380 ms (the N400 stage), negative deflections in left frontal, left anterior temporal, centrofrontal regions might coordinate and integrate both syntactic and semantic analysis in extensive right hemisphere; (3) during 480-540 ms (the P600 stage), positive deflections in left temporoparietal and occipital regions seemed to reflect the reanalysis and the integration of word meanings to obtain the over all meaning of idioms. Our study has implicated the brain mechanism of language comprehension common to alphabetic language as well as that specialized in logographic language.     

Scalp Topography and Intracerebral Sources for ERPs Recorded During Auditory Target Detection

Summary The goal of this study was to measure the scalp topography of the event-related potentials (ERPs) during the detection of improbable auditory targets and to determine the intracerebral sources of these potentials. ERPs were recorded when subjects listened to a sequence of spoken words and detected occasional (p = 0.2) targets defined either by the gender of the speaker (male/female) or the meaning of the word (animate/inanimate). Waveforms were evaluated in relation to category (target versus standard) and task (voice versus semantic). Dipole source analysis was performed using locations obtained from fMRI. Fronto-central negative waves (N450 and N600 ms) generated by sources in both the auditory cortex and frontal regions were larger for semantic tasks and larger over the left hemisphere. A large parieto-occipital positive wave (P700) occurring with a peak latency about 150 ms before the reaction time was mainly generated in the left temporo-parietal regions for the semantic task and bilaterally for the voice task. About 300 ms after the P700, a highly lateralized right temporo-parietal positive wave P1000r occurred with a source in the right temporo-parietal area. These results indicate three distinct physiological processes underlie the detection of auditory targets. Perceptual discrimination is related to interactions between the frontal and temporal regions, stimulus-response association occurs in the temporo-parietal regions and post-perceptual processing in the right temporo-parietal region.     

The brain basis of language processing: from structure to function

Language processing is a trait of human species. The knowledge about its neurobiological basis has been increased considerably over the past decades. Different brain regions in the left and right hemisphere have been identified to support particular language functions. Networks involving the temporal cortex and the inferior frontal cortex with a clear left lateralization were shown to support syntactic processes, whereas less lateralized temporo-frontal networks subserve semantic processes. These networks have been substantiated both by functional as well as by structural connectivity data. Electrophysiological measures indicate that within these networks syntactic processes of local structure building precede the assignment of grammatical and semantic relations in a sentence. Suprasegmental prosodic information overtly available in the acoustic language input is processed predominantly in a temporo-frontal network in the right hemisphere associated with a clear electrophysiological marker. Studies with patients suffering from lesions in the corpus callosum reveal that the posterior portion of this structure plays a crucial role in the interaction of syntactic and prosodic information during language processing.     

Visual and auditory alertness: modality-specific and supramodal neural mechanisms and their modulation by nicotine

Alertness is a nonselective attention component that refers to a state of general readiness that improves stimulus processing and response initiation. We used functional magnetic resonance imaging (fMRI) to identify neural correlates of visual and auditory alertness. A further aim was to investigate the modulatory effects of the cholinergic agonist nicotine. Nonsmoking participants were given either placebo or nicotine (NICORETTE gum, 2 mg) and performed a target-detection task with warned and unwarned trials in the visual and auditory modality. Our results provide evidence for modality-specific correlates of visual and auditory alertness in respective higher-level sensory cortices and in posterior parietal and frontal brain areas. The only region commonly involved in visual and auditory alertness was the right superior temporal gyrus. A connectivity analysis showed that this supramodal region exhibited modality-dependent coupling with respective higher sensory cortices. Nicotine was found to mainly decrease visual and auditory alertness-related activity in several brain regions, which was evident as a significant interaction of nicotine-induced decreases in BOLD signal in warned trials and increases in unwarned trials. The cholinergic drug also affected alerting-dependent activity in the supramodal right superior temporal gyrus; here the effect was the result of a significant increase of neural activity in unwarned trials. We conclude that the role of the right superior temporal gyrus is to induce an "alert" state in response to warning cues and thereby optimize stimulus processing and responding. We speculate that nicotine increases brain mechanisms of alertness specifically in conditions where no extrinsic warning is provided.     

Anticipatory attention to verbal and non-verbal stimuli is reflected in a modality-specific SPN

The time estimation paradigm allows the recording of anticipatory attention for an upcoming stimulus unconfounded by any anticipatory motor activity. Three seconds after a warning signal (WS) subjects have to press a button. A button press within a time window from 2,850 ms to 3,150 ms after the WS is considered ‘correct’, a movement prior to 2,850 ms after the WS is labelled ‘too early’ and a movement after 3,150 ms is labelled ‘too late’. Two seconds after the button press a Knowledge of Results (KR) stimulus is presented, informing the subject about the correctness of the response. Stimulus Preceding Negativity (SPN) is a slow wave which is recorded prior to the presentation of the KR stimulus. The SPN has a right hemisphere preponderance and is based upon activity in a network in which prefrontal cortex, the insula Reili and the parietal cortex are crucial. In the present study we asked two questions: (1) does the SPN show modality specificity and (2) does the use of verbal KR stimuli influence the right hemisphere preponderance? Auditory and visual stimuli were presented, in a verbal mode and in a non-verbal mode. SPN amplitudes prior to visual stimuli were larger over the visual cortex than prior to auditory stimuli. SPN amplitudes prior to auditory stimuli were larger over the frontal areas than prior to visual stimuli. The use of verbal stimuli did not influence the right hemisphere preponderance. We concluded that apart from the supramodal effect of KR stimuli in general, there is (first) a modality-specific activation of the relevant sensory cortical areas. The supramodal network underlying the attention for and the use of KR information is activated either from different sensory areas or from language processing cortical areas.     

Neuromagnetic recordings reveal the temporal dynamics of auditory spatial processing in the human cortex

In an attempt to delineate the assumed 'what' and 'where' processing streams, we studied the processing of spatial sound in the human cortex by using magnetoencephalography in the passive and active recording conditions and two kinds of spatial stimuli: individually constructed, highly realistic spatial (3D) stimuli and stimuli containing interaural time difference (ITD) cues only. The auditory P1m, N1m, and P2m responses of the event-related field were found to be sensitive to the direction of sound source in the azimuthal plane. In general, the right-hemispheric responses to spatial sounds were more prominent than the left-hemispheric ones. The right-hemispheric P1m and N1m responses peaked earlier for sound sources in the contralateral than for sources in the ipsilateral hemifield and the peak amplitudes of all responses reached their maxima for contralateral sound sources. The amplitude of the right-hemispheric P2m response reflected the degree of spatiality of sound, being twice as large for the 3D than ITD stimuli. The results indicate that the right hemisphere is specialized in the processing of spatial cues in the passive recording condition. Minimum current estimate (MCE) localization revealed that temporal areas were activated both in the active and passive condition. This initial activation, taking place at around 100 ms, was followed by parietal and frontal activity at 180 and 200 ms, respectively. The latter activations, however, were specific to attentional engagement and motor responding. This suggests that parietal activation reflects active responding to a spatial sound rather than auditory spatial processing as such.     

Cortico-cortical phase synchrony in auditory mismatch processing

Previous studies have shown a reduced MMN in patients with lesions in the temporal or frontal lobes, suggesting a temporal-frontal involvement in change detection. However, how the temporal lobe interacts with other brain areas in responding to unexpected deviant stimuli remains unclear. This study aimed to evaluate the functional connectivity between cerebral regions by measuring the phase synchrony of magnetoencephalographic (MEG) signals elicited by regular simple tones and their duration-deviants in an oddball paradigm. We measured MEG responses to deviant (1000-Hz frequency, 50-ms duration, probability of 15%) and standard (1000-Hz frequency, 100-ms duration) sounds in 10 healthy adults. By using the Morlet wavelet-based analysis, relative phase synchronization values of 4-40 Hz MEG responses at 150-300 ms after stimulus onset were calculated with respect to a reference channel from the temporal region. Phase synchronization was clearly identified between the temporal and ipsilateral frontal region in the auditory evoked responses. This temporal-frontal synchronization was significantly larger in deviants-elicited than standards-elicited activation at 4-25 Hz in the left hemisphere (p < 0.05), and at 4-8 Hz in the right hemisphere (p < 0.01). Also, temporal-temporal and temporal-parietal phase synchronies were found in deviants-evoked 4-8 Hz responses.The present results suggest an involvement of temporal-temporal, temporal-frontal, and temporal-parietal neuronal network in detecting auditory change. Phase synchronization analysis may provide a useful window to further understanding of the cerebral reactivity during the processing of auditory deviants.     

Dynamic Brain Activation Patterns for Face Recognition: A Magnetoencephalography Study

Summary: The present study used magnetoencephalography (MEG) to investigate the spatiotemporal profile of neurophysiological activity associated with recognition of recently encountered human faces in seventeen healthy right-handed adults. Activity sources modeled as instantaneous equivalent current dipoles were found in ventral occipito-temporal regions during the early stages of stimulus processing and in lateral temporal cortices during later stages. Hemispheric asymmetries in regional activity were restricted to ventral occipitotemporal areas. The magnitude of magnetic flux originating in these regions was greater in the right hemisphere during the first 350 ms post-stimulus onset. In addition, the duration of neurophysiological activity was greater in the right hemisphere after 600 ms post-stimulus onset. The results indicate right hemisphere predominance in the degree of engagement of neurophysiological processes involved in both the pre- and post-recognition phases of face processing. This research was supported in part by a grant from Epilepsy Foundation of America to D. Lee.     

Left hemispheric lateralization of brain activity during passive rhythm perception in musicians

The nature of hemispheric specialization of brain activity during rhythm processing remains poorly understood. The locus for rhythmic processing has been difficult to identify and there have been several contradictory findings. We therefore used functional magnetic resonance imaging to study passive rhythm perception to investigate the hypotheses that rhythm processing results in left hemispheric lateralization of brain activity and is affected by musical training. Twelve musicians and 12 nonmusicians listened to regular and random rhythmic patterns. Conjunction analysis revealed a shared network of neural structures (bilateral superior temporal areas, left inferior parietal lobule, and right frontal operculum) responsible for rhythm perception independent of musical background. In contrast, random-effects analysis showed greater left lateralization of brain activity in musicians compared to nonmusicians during regular rhythm perception, particularly within the perisylvian cortices (left frontal operculum, superior temporal gyrus, inferior parietal lobule). These results suggest that musical training leads to the employment of left-sided perisylvian brain areas, typically active during language comprehension, during passive rhythm perception.     

The time and space of lexicality: a neuromagnetic view

Illuminating the neural mechanisms subserving lexico-semantic processing is requisite to further understanding the neurophysiological basis of the dyslexias. Yet, despite numerous functional neuroimaging experiments, the location and temporal behavior of brain regions mediating word-level language processing remain an area of debate. Such investigations typically utilize the word/pseudoword contrast within hemodynamic measurements, and report several left hemisphere regions that respond more strongly to pseudowords but fail to replicate neural areas unique to real word processing. The present experiment addressed this problem from a different perspective. Mainly, we hypothesized that the time course, but not the neuroanatomy, would show within-subject across-condition disparities. For that purpose, we applied dipole-modeling techniques to high-density magnetoencephalographic recordings of healthy subjects, and utilized excellent spatiotemporal accuracy to demonstrate significant across-condition differences in the time domain, along with indistinguishable neural correlates within-subject. In all participants, both words and pseudowords elicited activity in left perisylvian language areas, with words consistently activating these regions ~100 ms earlier than pseudowords. Considerable functional heterogeneity was also observed, and this might underlie the inconsistencies among previous studies. We conclude that the neural distinction in word/pseudoword processing is not in spatial localization, but is better conceptualized as a dynamic difference in processing time.     

Hemispheric differences in auditory oddball responses during monaural versus binaural stimulation

Hemispheric lateralization of early event-related potentials (ERPs; e.g. N1) is largely based on anatomy of the afferent pathway; lateralization of later auditory ERPs (P2/N2, P250, P3b) is less clear. Using 257-channel EEG, the present study examined hemispheric laterality of auditory ERPs by comparing binaural and monaural versions of an auditory oddball task. N1 showed a contralateral bias over auditory cortex in both hemispheres as a function of ear of stimulation, although right hemisphere sources were activated regardless of which ear received input. Beginning around N1 and continuing through the time of P3b, right hemisphere temporal–parietal and frontal areas were more activated than their left hemisphere counterparts for stimulus evaluation/comparison and target detection. P250 and P3b component amplitudes, topographies, and source estimations were significantly influenced by ear of stimulation, with right hemisphere activity being stronger. This was particularly true for anterior temporal and inferior frontal sources which were more strongly associated with the later, more cognitive components (P250, P3b). Results are consistent with theories of a right hemisphere network that is prominently involved in sustained attention, stimulus evaluation, target detection, and working memory/context updating.     

Spatio–temporal dynamics of olfactory processing in the human brain: an event-related source imaging study

Although brain structures involved in central nervous olfactory processing in humans have been well identified with functional neuroimaging, little is known about the temporal sequence of their activation. We recorded olfactory event-related potentials (ERP) to H₂S stimuli presented to the left and right nostril in 12 healthy subjects. Topographic and source analysis identified four distinct processing steps between 200 and 1000 ms. Activation started ipsilateral to the stimulated nostril in the mesial and lateral temporal cortex (amygdala, parahippocampal gyrus, superior temporal gyrus, insula). Subsequently, the corresponding structures on the contralateral side became involved, followed by frontal structures at the end of the activation period. Thus, based on EEG-related data, current results suggest that olfactory information in humans is processed first ipsilaterally to the stimulated nostril and then activates the major relays in olfactory information processing in both hemispheres. Most importantly, the currently described techniques allow the investigation of the spatial processing of olfactory information at a high temporal resolution.     

Frontal and temporal lobe sources for a marker of controlled auditory attention: the negative difference (Nd) event-related potential

Frontal and temporal lobe sources for electrical activity associated with auditory controlled attention (negative difference, Nd) were sought for comparison with those reported to arise from the earlier detection of stimulus-change (mismatch negativity, MMN: Jemel et al. 2002). In two sessions a month apart (T1 and T2), 14 subjects were presented with a 3-tone oddball passively, then as a discrimination task. In EEG recordings (32 sites), Nd was calculated by subtraction of the event-related potential elicited by a non-attended stimulus from that after the same frequency-deviant as target. Putative generators in the 180-228 ms latency-range were modelled with brain electrical source analysis and mapped to the modified Montreal brain-atlas. Initial T1-analyses located bilateral Nd dipoles in the superior temporal gyrus (BA22) and the dorsolateral prefrontal cortex (BA8). Re-test allowed estimates of the temporal and spatial extension of activity. Peak activity occurred 14 ms later. Step-by-step analysis showed that the best spatial fit for the inverse-solutions extended 3-6 mm from the point sources, but for temporal lobe sources this increased 15 mm caudally. The right mid-frontal source (BA10) was rostral and ventral from that in the left superior frontal gyrus (BA8). T1 and T2 dipole strengths were well correlated. Nd measures of controlled attention localised to areas associated with sustained attention, problem-solving and working-memory. Temporal lobe sources were later and more posterior and medial than for automatic change-detection. Frontal Nd sources were more dorsal on the right and more rostral on the left than MMN dipoles reported for the right inferior frontal and left anterior cingulate. The sequence of information processing is reviewed.     

MEG study on neural activities associated with syntactic and semantic violations in spoken Korean sentences

We carried out an magnetoencephalography (MEG) study to record cortical responses elicited in the left hemisphere by ending verb phrases, which had syntactic or semantic anomalies, in Korean sentences of subject-object-verb order. Using the high temporal and spatial resolution of MEG, the study was aimed at identifying neural activities that occur during a latency course associated with the syntactic or semantic process in the spoken sentence. Major responses, distinct from the responses to normal sentences, were observed in two latency periods of about 400 and 600 ms following the onset of the verb phrase. Source localization of the grand average fields indicated separate activities in the inferior frontal region and the vicinity of the auditory cortex for the first 400-ms response to the syntactic anomaly. The region around the auditory cortex was indicated for the response to the semantic anomaly in a similar latency. The second 600-ms response indicated activity around the middle temporal gyrus inferior to the auditory cortex for both syntactic and semantic anomalies. The results are discussed with reference to the ERP components established for Indo-European languages, and the possibility of concurrent processing of syntactic and semantic aspects is suggested.     

Processing of temporal information and the basal ganglia: new evidence from fMRI

Temporal information processing is a fundamental brain function, which might include central timekeeping mechanisms independent of sensory modality. Psychopharmacological and patient studies suggest a crucial role of the basal ganglia in time estimation. In this study, functional magnetic resonance imaging (fMRI) was applied in 15 healthy right-handed male subjects performing an auditory time estimation task (duration discrimination of tone pairs in the range of 1,000–1,400 ms) and frequency discriminations (tone pairs differing in pitch, around 1,000 Hz) as an active control task. Task difficulty was constantly modulated by an adaptive algorithm (weighted up-down method) reacting on individual performance. Time estimation (vs rest condition) elicited a distinct pattern of cerebral activity, including the right medial and both left and right dorsolateral prefrontal cortices (DLPFC), thalamus, basal ganglia (caudate nucleus and putamen), left anterior cingulate cortex, and superior temporal auditory areas. Most activations showed lateralisation to the right hemisphere and were similar in the frequency discrimination task. Comparing time and frequency tasks, we isolated activation in the right putamen restricted to time estimation only. This result supports the notion of central processing of temporal information associated with basal ganglia activity. Temporal information processing in the brain might thus be a distributed process of interaction between modality-dependent sensory cortical function, the putamen (with a timing-specific function), and additional prefrontal cortical systems related to attention and memory. Further investigations are needed to delineate the differential contributions of the striatum and other areas to timing. Electronic Publication     

Effect of the diurnal rhythm and 24 h of sleep deprivation on dichotic temporal order judgment

The present study examined the impact of mild (24 h) sleep deprivation and of the circadian rhythm on auditory temporal resolution, measured by dichotic temporal order judgment (TOJ). The rationale for the present study was based on several areas of research. First, the 'sleep-based neuropsychological perspective' hypothesis posits that sleep reduction initially impacts the functions associated with intact prefrontal cortical activity, e.g. language tasks. Secondly, recent studies indicate the importance of the role of auditory temporal resolution in speech comprehension. Thirdly, there is accumulating evidence of the involvement of prefrontal cortical structures in auditory temporal resolution. We hypothesized that mild to moderate sleep deprivation would affect dichotic TOJ negatively. The results showed that: (1) 24 h of sleep deprivation significantly reduced the overall level of accuracy in dichotic TOJ and increased dichotic TOJ threshold from 57.61 ms to 73.93 ms, a reduction in temporal resolution of 28.3%; (2) dichotic TOJ was subject to a small, but significant diurnal rhythm having a nadir in early to mid afternoon. As auditory temporal resolution of speech and non-speech sounds seems to be dependent on intact functioning of the left inferior and left dorso-lateral prefrontal cortex (PFC), these data strengthen the argument that even mild to moderate sleep deprivation can impact negatively on PFC-dependent functions. Furthermore, based on these findings, we suggest that the deficit in auditory temporal resolution in individuals suffering from sleep loss may also affect language comprehension.     

Aberrant spatiotemporal activation profiles associated with math difficulties in children: a magnetic source imaging study

The study investigates the relative degree and timing of cortical activation in parietal, temporal, and frontal regions during simple arithmetic tasks in children who experience math difficulties. Real-time brain activity was measured with magnetoencephalography during simple addition and numerosity judgments in students with math difficulties and average or above average reading skills (MD group, N = 14), students with below average scores on both math and basic reading tests (MD/RD group, N = 16) and students with above average scores on standardized math tests (control group, N = 25). Children with MD showed increased degree of neurophysiological activity in inferior and superior parietal regions in the right hemisphere compared to both controls and MD/RD students. Left hemisphere inferior parietal regions did not show the expected task-related changes and showed activity at a significant temporal delay. MD students also showed increased early engagement of prefrontal cortices. Taken together, these findings may indicate increased reliance on a network of right hemisphere parietal (and possibly frontal areas as well) for simple math calculations in students who experience math difficulties but perform within normal range in reading.     

Lateralization of Cerebral Activation in Auditory Verbal and Non-Verbal Memory Tasks Using Magnetoencephalography

The magnetic flux normal to the scalp surface was measured with a whole-head neuromagnetometer while right-handed subjects (N = 15) were engaged in either an auditory word- or a tone-recognition task. Sources of the recorded magnetic fields were modeled as equivalent current dipoles at 4 ms intervals and the number of sources in the later portion of the magnetic response was used as an index of the degree of brain activation. Significantly more sources were found in the left as compared to the right hemisphere in the word but not the tone task on a group basis. On an individual basis, 13/15 subjects had more sources in the left as compared to the right hemisphere during the word task, while in the tone task 3/10 subjects showed this pattern. Sources of activity were found in the left superior and middle temporal gyri in all subjects with available MRI scans. Sources were also found in the supramarginal gyrus and in medial temporal areas, including the hippocampus, in the majority of cases. MEG appears to be a promising tool for detecting activity in cerebral areas specialized for language and memory function.