Fu-Jung Hsiao

Theta oscillation during auditory change detection: An MEG study

To study the phase and power characteristics of brain oscillations during the preattentive detection of auditory deviance, we recorded magnetoencephalographic responses in 10 healthy subjects with an oddball paradigm. As the subject was watching a silent movie, standard tones (1000-Hz frequency, 100-ms duration) and their duration deviants (50-ms duration, probability of 15%) were randomly delivered binaurally. In addition to localizing the magnetic counterpart of mismatch negativity (MMNm) with equivalent current dipole modeling, we also measured the phase-locking value (PLV) and power change of the oscillatory responses to standard and deviant stimuli by employing the Morlet wavelet-based analysis. The MMNm signals peaking at 150-200ms after the onset of deviant were localized in bilateral temporal regions with larger amplitudes in the right hemisphere. Then 50ms after the onset of either standard or deviant stimuli, we observed an increase of PLV and power of theta and alpha oscillations in bilateral temporal regions. PLVs of theta and alpha activities to deviant stimuli were significantly larger in the right than left hemisphere (P<0.001). Compared with standard stimuli, deviants elicited a larger theta PLV (P<0.001) at 150-300ms and a larger theta power change (P<0.05) at 50-300ms for the responses in the right temporal region. In addition, a prominent theta phase-locking of deviant-elicited responses was found in the right frontal area at 110-250ms (P<0.01). Our current data suggest that a pronounced phase and power modulation on sound-elicited theta oscillations might characterize the change detection processing in the temporo-frontal network as reflected by the mismatch negativity.

Altered Oscillation and Synchronization of Default-Mode Network Activity in Mild Alzheimer’s Disease Compared to Mild Cognitive Impairment: An Electrophysiological Study

Some researchers have suggested that the default mode network (DMN) plays an important role in the pathological mechanisms of Alzheimer’s disease (AD). To examine whether the cortical activities in DMN regions show significant difference between mild AD from mild cognitive impairment (MCI), electrophysiological responses were analyzed from 21 mild Alzheimer’s disease (AD) and 21 mild cognitive impairment (MCI) patients during an eyes closed, resting-state condition. The spectral power and functional connectivity of the DMN were estimated using a minimum norm estimate (MNE) combined with fast Fourier transform and imaginary coherence analysis. Our results indicated that source-based EEG maps of resting-state activity showed alterations of cortical spectral power in mild AD when compared to MCI. These alterations are characteristic of attenuated alpha or beta activities in the DMN, as are enhanced delta or theta activities in the medial temporal, inferior parietal, posterior cingulate cortex and precuneus. With regard to altered synchronization in AD, altered functional interconnections were observed as specific connectivity patterns of connection hubs in the precuneus, posterior cingulate cortex, anterior cingulate cortex and medial temporal regions. Moreover, posterior theta and alpha power and altered connectivity in the medial temporal lobe correlated significantly with scores obtained on the Mini-Mental State Examination (MMSE). In conclusion, EEG is a useful tool for investigating the DMN in the brain and differentiating early stage AD and MCI patients. This is a promising finding; however, further large-scale studies are needed.

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.

The effects of face spatial frequencies on cortical processing revealed by magnetoencephalography

To study the spatial frequency (SF) effects on cortical face processing, we recorded magnetoencephalographic responses in seven healthy subjects to upright and inverted human faces. Four face types were used, including original (broad-band SF, BSF), low SF (LSF, <5 cycles/face), middle SF (MSF, 5-15 cycles/face), and high SF (HSF, >15 cycles/face) face images. Using equivalent current dipole (ECD) modeling, neuromagnetic M170 responses peaking around 160-185 ms were localized in right occipitotemporal region across subjects to BSF faces. M170 responses to LSF faces showed longer latency and smaller amplitude compared with those to BSF faces. We found no significant difference between BSF, MSF, and HSF conditions in M170 amplitude or latency. ECD locations for the four upright face conditions were close to one another, although the mean locations for MSF or HSF seemed more medial than those for BSF or LSF. Longer latencies for inverted than upright faces were observed in BSF (183.4+/-8.5 ms versus 168+/-6.9 ms, P<0.001) and LSF face conditions (223.6+/-13.1 ms versus 207.3+/-16.3 ms, P<0.01). M170 ECDs were located more medial for inverted than upright images in either BSF or LSF condition. In conclusion, the less M170 activation to LSF faces suggests that face parts information is important for early face processing. The cortical representations in right occipitotemporal region for configural and face feature processing are overlapping. Our findings on the face inversion effect suggest that inverted BSF and LSF faces may be processed as objects.

Neural correlates of somatosensory paired-pulse suppression: A MEG study using distributed source modeling and dynamic spectral power analysis

Paired-pulse stimulation has been used previously to evaluate cortical excitability and sensory gating. To help elucidate the neural network involved in paired-pulse suppression of somatosensory cortical processing, magnetoencephalographic (MEG) responses to paired-pulse electrical stimulation of the left median nerve of the wrists of 13 healthy males were recorded using an intra-pair interstimulus interval (ISI) of 500ms and an inter-pair ISI of 8s. Minimum norm estimates showed the presence of cortical activation in the bilateral primary somatosensory cortex, the post-central sulcus and the supplementary motor areas. Compared with the responses to the first stimulation, the responses to the second stimulation were attenuated in these areas with gating ratios (the amplitude ratios of the second response to the first response) of 0.54-0.69. By spectral power dynamic analysis, beta frequency oscillations were found to be associated with an early-latency (30-36ms) gating process in the contralateral primary somatosensory cortex and post-central sulcus, whereas theta and alpha oscillations were correlated with paired-pulse suppression of activations at 98-136ms in the ipsilateral primary somatosensory cortex, the bilateral post-central sulcus and the supplementary motor areas. In summary, it can be concluded that differential oscillatory activities are involved in the pair-pulse suppression in various somatosensory regions in response to repetitive external stimulations.

Increased Intrinsic Connectivity of the Default Mode Network in Temporal Lobe Epilepsy: Evidence from Resting-State MEG Recordings

The electrophysiological signature of resting state oscillatory functional connectivity within the default mode network (DMN) during spike-free periods in temporal lobe epilepsy (TLE) remains unclear. Using magnetoencephalographic (MEG) recordings, this study investigated how the connectivity within the DMN was altered in TLE, and we examined the effect of lateralized TLE on functional connectivity. Sixteen medically intractable TLE patients and 22 controls participated in this study. Whole-scalp 306-channel MEG epochs without interictal spikes generated from both MEG and EEG data were analyzed using a minimum norm estimate (MNE) and source-based imaginary coherence analysis. With this processing, we obtained the cortical activation and functional connectivity within the DMN. The functional connectivity was increased between DMN and the right medial temporal (MT) region at the delta band and between DMN and the bilateral anterior cingulate cortex (ACC) regions at the theta band. The functional change was associated with the lateralization of TLE. The right TLE showed enhanced DMN connectivity with the right MT while the left TLE demonstrated increased DMN connectivity with the bilateral MT. There was no lateralization effect of TLE upon the DMN connectivity with ACC. These findings suggest that the resting-state functional connectivity within the DMN is reinforced in temporal lobe epilepsy during spike-free periods. Future studies are needed to examine if the altered functional connectivity can be used as a biomarker for treatment responses, cognitive dysfunction and prognosis in patients with TLE.

Effects of aging on neuromagnetic mismatch responses to pitch changes

Although aging-related alterations in the auditory sensory memory and involuntary change discrimination have been widely studied, it remains controversial whether the mismatch negativity (MMN) or its magnetic counterpart (MMNm) is modulated by physiological aging. This study aimed to examine the effects of aging on mismatch activity to pitch deviants by using a whole-head magnetoencephalography (MEG) together with distributed source modeling analysis. The neuromagnetic responses to oddball paradigms consisting of standards (1000 Hz, p=0.85) and deviants (1100 Hz, p=0.15) were recorded in healthy young (n=20) and aged (n=18) male adults. We used minimum norm estimate of source reconstruction to characterize the spatiotemporal neural dynamics of MMNm responses. Distributed activations to MMNm were identified in the bilateral fronto-temporo-parietal areas. Compared to younger participants, the elderly exhibited a significant reduction of cortical activation in bilateral superior temporal guri, superior temporal sulci, inferior fontal gyri, orbitofrontal cortices and right inferior parietal lobules. In conclusion, our results suggest an aging-related decline in auditory sensory memory and automatic change detection as indexed by MMNm.

Altered source-based EEG coherence of resting-state sensorimotor network in early-stage Alzheimer's disease compared to mild cognitive impairment

Although the altered coherence between cortical areas in Alzheimers disease (AD) has been widely studied, it remains unclear whether the source-based coherence measures within sensorimotor network show significant difference between mild cognitive impairment (MCI) and AD. In the present study, resting-state electroencephalographic signals were recorded from 21 MCI and 21 mild AD patients. The spectral power and coherence in the sensorimotor areas were analyzed using the minimum norm estimate (MNE) combined with fast Fourier transform and coherence analysis in delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-25 Hz), and gamma (25-40 Hz) bands. Our results indicated that source-based coherence in AD showed increased delta coherences between the bilateral precentral, left supplementary motor area (SMA) and right precentral, and left SMA and right postcentral areas. However, no significant difference of spectral powers was observed between AD and MCI. To conclude, the phenotype conversion from MCI to AD may be associated with an altered connectivity of the sensorimotor cortical network. This is a promising finding; however, further large-scale studies are needed.

Effects of aging on the neuromagnetic mismatch detection to speech sounds.

The ability to discriminate speech sounds is crucial for higher language functions in humans. However, it remains unclear whether physiological aging affects the functional integrity of pre-attentive phonological discrimination. The neuromagnetic cortical responses during automatic change detection of speech sounds (/ba/versus/da/) were recorded in 24 young and 21 aged male adults. We used minimum norm estimate of source reconstruction to characterize the spatiotemporal dynamics of magnetic mismatch responses (MMNm). Distributed activations to phonetic changes were identified in the temporal, frontal and parietal regions. Compared to younger participants, elderly volunteers exhibited a significant reduction of cortical responses to phonetic-MMNm, except for the left orbitofrontal cortex and anterior inferior temporal gyrus. However, among the identified regions of interest, we did not observe significant between-group differences in the hemispheric asymmetry of phonetic-MMNm. Conclusively, our results suggest an altered phonetic processing at the perceptual level during physiological aging.

Bilateral oscillations for lateralized spikes in benign rolandic epilepsy

PURPOSES To elucidate the oscillatory dynamics with respect to interictal spike occurrence in benign rolandic epilepsy (BRE). METHODS Using a whole-scalp magnetoencephalography (MEG), we recorded scalp EEG and MEG signals in 10 BRE patients (age 8-12 years) and visually identified unilateral interictal spikes that were simultaneously present on both EEG and MEG channels. We obtained the peak timing of individual spike complex based on MEG single-dipole modeling, and then applied wavelet transform to analyze the time-frequency components of corresponding MEG signals with respect to spike occurrence. RESULTS In the hemisphere with time-domain spike waveforms, we identified a clear increase of 0.5-40 Hz activity around the spike peak, most prominent at alpha band (8-13 Hz). Notably, at the approximate timing we also observed an increase in 0.5-25 Hz oscillations over the homotopic area in the other hemisphere where no spike signals were found. CONCLUSIONS Our results indicate bilateral increases in 0.5-25 Hz oscillations during unilateral spike formation in BRE patients. By using wavelet transform analysis, one could be able to detect some irritative feature that would in visual analysis remain undetected.