Effects of NMDA receptor antagonist memantine on mismatch negativity

Mismatch negativity (MMN) and its magnetic counterpart (MMNm) have been shown to be altered in patients with various psychiatric and neurological disorders, e.g. Alzheimer's disease and schizophrenia, indicating deficits in involuntary attention. N-Methyl-D-aspartate (NMDA) receptor-mediated glutamate dysfunction is suggested to underlie these deficits. However, the role of NMDA receptors in involuntary attention is poorly understood. Memantine is an NMDA receptor antagonist that has been demonstrated to be effective in the treatment of patients with Alzheimer's disease. We aimed to investigate whether a single dose of memantine would affect MMN/MMNm in healthy subjects studied with simultaneous electroencephalography (EEG) and magnetoencephalography (MEG). Monaural left-ear auditory stimuli were presented in a passive oddball paradigm with infrequent deviant tones differing in frequency and duration. Neuronal activity was recorded in 13 healthy subjects after oral administration of 30mg of memantine or placebo in a randomized, double-blind, cross-over design. MMNm was analyzed using equivalent current dipoles. MMN was evaluated from frontocentral electrodes. Memantine lowered subjects' arousal level as measured by visual analog scales, and enhanced the amplitude of MMN in EEG. No differences in MMN latency were observed in MEG or EEG. Memantine did not affect the location, strength, amplitude or latency of MMNm, P1m, and N1m components. No changes in amplitude or latency were observed for P1 and N1 peaks. These results indicate that memantine affects involuntary attention without otherwise changing auditory processing of the stimuli. As memantine-induced changes in MMN were detected only in EEG, we suggest that the effect is mostly related to the frontal cortex.     

Utility of magnetoencephalography in the evaluation of recurrent seizures after epilepsy surgery

PURPOSE: To study the role of magnetoencephalography (MEG) in the surgical evaluation of children with recurrent seizures after epilepsy surgery. METHODS: We studied 17 children with recurrent seizures after epilepsy surgery using interictal and ictal scalp EEG, intracranial video EEG (IVEEG), MRI, and MEG. We analyzed the location and distribution of MEG spike sources (MEGSSs) and the relationship of MEGSSs to the margins of previous resections and surgical outcome. RESULTS: Clustered MEGSSs occurred at the margins of previous resections within two contiguous gyri in 10 patients (group A), extended spatially from a margin by < or =3 cm in three patients (group B), and were remote from a resection margin by >3 cm in six patients (group C). Two patients had concomitant group A and C clusters. Thirteen patients underwent second surgeries. IVEEG was used in four patients. Six of seven patients with group A MEGSS clusters did not require IVEEG for second surgeries. Follow-up periods ranged from 0.6 to 4.3 years (mean: 2.6 years). Eleven children, including eight who became seizure-free, achieved Engel class I or II. CONCLUSION: Our data demonstrate the utility of MEG for evaluating patients with recurrent seizures after epilepsy surgery. Specific MEGSS cluster patterns delineate epileptogenic zones. Removing cluster regions adjacent to the margins of previous resections, in addition to removing recurrent lesions, achieves favorable surgical outcome. Cluster location and extent identify which patients require IVEEG, potentially eliminating IVEEG for some. Patients with remotely located clusters require IVEEG for accurate assessment and localization of the entire epileptogenic zone.     

Dissociation of summation and peak latencies in visual processing: An MEG study on stimulus eccentricity

Research on the temporal characteristics of visual processing, as measured with critical flicker fusion or the latency of visual evoked potential (VEP), shows controversial results if different eccentricities of visual stimuli are compared. To clarify this question, a direct measure of cortical activity with magnetoencephalography (MEG) was applied to examine the neuronal summation latency and peak latency for both near and far peripheral stimuli. Consistent with cortical magnification, the peak amplitude for less eccentric stimuli was larger than that for more eccentric stimuli. More importantly, the current data also demonstrated longer cortical summation latency and peak latency for more eccentric visual stimuli, but only the summation latency difference between near and far stimuli correlated with the peak amplitude difference between near and far stimuli. These results suggest dissociable mechanisms of summation latency and peak latency with respect to their contributions to the stimulus eccentricity effect, and provide potential explanations for controversial results in previous studies.     

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.     

抑郁症患者识别悲伤表情刺激时磁源性影像动态变化的性别差异

目的 本研究利用脑磁图(MEG)技术以及表情类型识别实验范式来探讨抑郁症患者识别面部悲伤动态表情时功能网络神经基础的性别差异.方法 利用脑磁图检测12例女性抑郁症患者以及11名年龄、受教育年限相匹配的男性抑郁症患者以及正常对照者识别动态表情视频时的脑部反应.结果 与男性抑郁症患者相较,女性抑郁症患者识别面部悲伤动态表情时活动增强的脑区依次为双侧额下回(x,y,z=58/-60,12/22,20/20,T=2.17,1.88)、左前扣带回(x,y,z=64,12,4,T=2.37)、双侧额上回(x,y,z=30/-24,64/-4,0/50,T=2.86,2.36)、左脑干(x,y,z=-12,-16,-18,T=1.96)、右额中回(x,y,z=40,60,4,T=2.22)、双侧中央前回(x,y,z=-62/56,16/10,10/8.T=1.99,2.65)、左海马(x,y,z=-26,-14,-20,T=1.77)、左海马旁回(x,y,z=-16,-12,-20,T=1.72)、右枕中回(x,y,z=50,-76,-14,T=1.75)等;活动减弱的脑区依次为右颞上回(x,y,z=68,-18,2,T=1.85)、右海马旁回(x,y,z=20,-36,-14,T=1.92)、左楔叶(x,y,z=-6,-98,14,T=2.46)、双侧颞中回(x,y,z=52/-34,-80/-62,20/28,T=1.95,2.57)、左楔前叶(x,y,z=-40,-74,38,T=2.58)、右海马旁回(x,y,z=24,-32,-18,T=2.05)等.设P＜0.05时,均差异具有显著性.结论 本研究结果提示抑郁症患者的悲伤情绪识别功能网络存在显著的性别差异.

Abstract：

Objective To explore the gender differences of brain activation between patients with depression in recognition of dynamically sad expression with magnetoencephalography (MEG) technology and the paradigm of expressional experiment,and further to examine its neurological basis. Methods Brain activities were detected using MEG during the recognition of dynamic facial video with 12 female depressed patients, 11 male depressed patients, and their corresponding normal controls matched by age and education. Results Compared with male depression,female depression showed increased activation during different time periods were in turn as follows: bilateral inferior frontal gyrus ( x, y, z = 58/- 60,12/22,20/20, T = 2.17,1.88 ), left anterior cingulate gyrus ( x, y, z = 64,12,4, T = 2.37 ), bilateral superior frontal gyrus ( x, y, z= 30/-24,64/- 4,0/50, T = 2.86,2.36 ),the left brainstem( x, y,z = - 12, - 16, - 18 ,T = 1.96) ,right middle frontal gyrus( x,y,z =40,60,4,T = 2.22 ),bilateral precentral gyrus(x,y,z = -62/56, 16/10, 10/8. T = 1.99,2.65 ) ,left hippocampus ( x,y,z = - 26,- 14, -20,T = 1.77) ,left parahippocampal gyrus(x,y,z = - 16, - 12, -20,T = 1.72) ,right middle occipital gyrus( x ,y ,z = 50, -76, -14 ,T = 1. 75 ),while the decreased brain activation were in turn in right superior temporal gyrus ( x, y, z = 68, - 18,2, T = 1.85 ), right parahippocampal gyrus ( x, y, z = 20, - 36, - 14, T = 1.92 ), left cuneus( x,y,z = -6, -98,14,T =2.46) ,bilateral temporal middle gyrus( x,y,z =52/-34, - 80/-62,20/28,T = 1.95,2.57 ), left pre-cuneus ( x, y, z = - 40, - 74,38, T = 2.58 ), right hippocampus( x, y, z = 24, - 32, - 18,T = 2.05 ) in recognition of dynamically sad expression. ( p ＜ 0. 05, corrected). Conclusion The data suggest that there may be significant gender differences of functional network in depressed patients during recognizing dynamical sad facial expression.     

Sex differences in sensorimotor mu rhythms during selective attentional processing

We used magnetoencephalography to investigate the effect of directed attention on sensorimotor mu (8–12 Hz) response (mu reactivity) to non-painful electrical stimulation of the median nerve in healthy adults. Mu desynchronization in the 10–12 Hz bandwidth is typically observed during higher-order cognitive functions including selective attentional processing of sensorimotor information (Pfurtscheller, Neuper, & Krauz, 2000). We found attention-related sex differences in mu reactivity, with females showing (i) prolonged mu desynchrony when attending to somatosensory stimuli, (ii) attentional modulation of the mu response based on whether attention was directed towards or away from somatosensory stimuli, which was absent in males, and (iii) a trend for greater neuronal excitability of the primary somatosensory region suggesting greater physiological responsiveness to sensory stimulation overall. Our findings suggest sex differences in attentional control strategies when processing somatosensory stimuli, whose salience may be greater for females. These sex differences in attention to somatosensory stimuli may help elucidate the well-documented sex biases in pain processing wherein females typically report greater sensitivity to experimental and clinical pain.     

A shared cortical bottleneck underlying Attentional Blink and Psychological Refractory Period

Doing two things at once is difficult. When two tasks have to be performed within a short interval, the second is sharply delayed, an effect called the Psychological Refractory Period (PRP). Similarly, when two successive visual targets are briefly flashed, people may fail to detect the second target (Attentional Blink or AB). Although AB and PRP are typically studied in very different paradigms, a recent detailed neuromimetic model suggests that both might arise from the same serial stage during which stimuli gain access to consciousness and, as a result, can be arbitrarily routed to any other appropriate processor. Here, in agreement with this model, we demonstrate that AB and PRP can be obtained on alternate trials of the same cross-modal paradigm and result from limitations in the same brain mechanisms. We asked participants to respond as fast as possible to an auditory target T1 and then to a visual target T2 embedded in a series of distractors, while brain activity was recorded with magneto-encephalography (MEG). For identical stimuli, we observed a mixture of blinked trials, where T2 was entirely missed, and PRP trials, where T2 processing was delayed. MEG recordings showed that PRP and blinked trials underwent identical sensory processing in visual occipito-temporal cortices, even including the non-conscious separation of targets from distractors. However, late activations in frontal cortex (> 350 ms), strongly influenced by the speed of task-1 execution, were delayed in PRP trials and absent in blinked trials. Our findings suggest that PRP and AB arise from similar cortical stages, can occur with the same exact stimuli, and are merely distinguished by trial-by-trial fluctuations in task processing.     

Neuronal network coherent with hand kinematics during fast repetitive hand movements

We quantified the coupling between magnetoencephalographic (MEG) cortical signals and the kinematics of fast repetitive voluntary hand movements monitored by a 3-axis accelerometer. Ten healthy right-handed adults performed self-paced flexion-extension movements of right-hand fingers at ~ 3 Hz with either touching the thumb during flexions (TOUCH) or not (noTOUCH). At the sensor level, we found in all subjects and conditions significant coherence at the movement frequency (F0) and its first harmonic (F1). Coherence values were significantly higher in TOUCH compared to noTOUCH. At the group level, dynamic imaging of coherent sources localized the main source of coherent activity at the left primary motor (M1) hand area, except at F0 TOUCH were the main source was localized at the left primary sensory (S1) hand area. Other coherent brain areas were also identified at right S1-M1 cortices (F0), left dorsolateral prefrontal cortex (F1), left posterior parietal cortex (F0 TOUCH and F1 noTOUCH) and left medial S1-M1 areas (TOUCH). This study highlights the prominent role of rhythmic neuronal activity phase-locked to movements for the encoding and the integration of key sensori-motor features of limb kinematics. This study also suggests that somatosensory afferences play a key role to sustain a high synchronization level between the neuronal activity in coherent brain areas and hand acceleration. Some coherent brain regions differed between F0 and F1 in both conditions, suggesting that distinct cortical areas are involved in different features of hand kinematics.     

Magnetoencephalography in pediatric lesional epilepsy surgery

This study was performed to assess the usefulness of magnetoencephalography (MEG) as a presurgical evaluation modality in Korean pediatric patients with lesional localization-related epilepsy. The medical records and MEG findings of 13 pediatric patients (6 boys and 7 girls) with localization-related epilepsy, who underwent epilepsy surgery at Seoul National University Children's Hospital, were retrospectively reviewed. The hemispheric concordance rate was 100% (13/13 patients). The lobar or regional concordance rate was 77% (10/13 patients). In most cases, the MEG spike sources were clustered in the proximity of the lesion, either at one side of the margin (nine patients) or around the lesion (one patient); clustered spike sources were distant from the lesion in one patient. Among the patients with clustered spike sources near the lesion, further extensions (three patients) and distal scatters (three patients) were also observed. MEG spike sources were well lateralized and localized even in two patients without focal epileptiform discharges in the interictal scalp electroencephalography. Ten patients (77%) achieved Engel class I postsurgical seizure outcome. It is suggested that MEG is a safe and useful presurgical evaluation modality in pediatric patients with lesion localization-related epilepsy.     

基于PCA和LDA数据降维的脑磁图脑机接口研究

脑磁图(MEG)信号作为一种新的脑-机接口(BCI)输入信号,含有手运动方向的模式信息。通常对MEG信号采用信号处理的特征提取和线性分类,识别率一直难于提高。本文提出用主成分分析(PCA)方法对其进行特征提取,并用线性判别分析(LDA)进行了优化,最后用最近邻非线性分类器进行分类,在分类结果的基础上分析了混淆矩阵。实验结果表明PCA+LDA方法能有效的分析多通道的MEG信号,平均识别率达到了53.0%,优于BCI竞赛Ⅳ的识别率46.9%。