Reciprocal modulation of neuromagnetic induced gamma activity by attention in the human visual and auditory cortex

For attentional control of behavior, the brain permanently resolves a competition between the impressions supplied by different senses. Here, using a dual-modality temporal order detection task, we studied attentional modulation of oscillatory neuromagnetic activity in the human cerebral cortex. On each trial, after simultaneous exposure to visual and auditory noise, subjects were presented with an asynchronous pair of a visual and an auditory stimulus. Either of the two stimuli could occur first equally often, their order was not cued. Subjects had to determine the leading stimulus in a pair and attentively monitor it to respond upon its offset. With the attended visual or auditory stimuli, spectral power analysis revealed marked enhancements of induced gamma activity within 250 ms post-stimulus onset over the modality-specific cortices (occipital at 64 Hz, right temporal at 53 Hz). When unattended, however, the stimuli led to a significantly decreased (beneath baseline) gamma response in these cortical regions. The gamma decreases occurred at lower frequencies ( approximately 30 Hz) than did the gamma increases. An increase in the gamma power and frequency for the attended modality and their decrease for the unattended modality suggest that attentional regulation of multisensory processing involves reciprocal changes in synchronization of respective cortical networks. We assume that the gamma decrease reflects an active suppression of the task-irrelevant sensory input. This suppression occurs at lower frequencies, suggesting an involvement of larger scale cell assemblies.     

Attentional modulation of oscillatory activity in human visual cortex

The effects of attentional modulation on activity within the human visual cortex were investigated using magnetoencephalography. Chromatic sinusoidal stimuli were used to evoke activity from the occipital cortex, with attention directed either toward or away from the stimulus using a bar-orientation judgment task. For five observers, global magnetic field power was plotted as a function of time from stimulus onset. The major peak of each function occurred at about 120 ms latency and was well modeled by a current dipole near the calcarine sulcus. Independent component analysis (ICA) on the non-averaged data for each observer also revealed one component of calcarine origin, the location of which matched that of the dipolar source determined from the averaged data. For two observers, ICA revealed a second component near the parieto-occipital sulcus. Although no effects of attention were evident using standard averaging procedures, time-varying spectral analyses of single trials revealed that the main effect of attention was to alter the level of oscillatory activity. Most notably, a sustained increase in alpha-band (7-12 Hz) activity of both calcarine and parieto-occipital origin was evident. In addition, calcarine activity in the range of 13-21 Hz was enhanced, while calcarine activity in the range of 5-6 Hz was reduced. Our results are consistent with the hypothesis that attentional modulation affects neural processing within the calcarine and parieto-occipital cortex by altering the amplitude of alpha-band activity and other natural brain rhythms.     

Self-paced movements induce high-frequency gamma oscillations in primary motor cortex

There has been increasing interest in the functional role of high-frequency (>30 Hz) cortical oscillations accompanying various sensorimotor and cognitive tasks in humans. Similar "high gamma" activity has been observed in the motor cortex, although the role of this activity in motor control is unknown. Using whole-head MEG recordings combined with advanced source localization methods, we identified high-frequency (65 to 80 Hz) gamma oscillations in the primary motor cortex during self-paced movements of the upper and lower limbs. Brief bursts of gamma activity were localized to the contralateral precentral gyrus (MI) during self-paced index finger abductions, elbow flexions and foot dorsiflexions. In comparison to lower frequency (10-30 Hz) sensorimotor rhythms that are bilaterally suppressed prior to and during movement (Jurkiewicz et al., 2006), high gamma activity increased only during movement, reaching maximal increase 100 to 250 ms following EMG onset, and was lateralized to contralateral MI, similar to findings from intracranial EEG studies. Peak frequency of gamma activity was significantly lower during foot dorsiflexion (67.4+/-5.2 Hz) than during finger abduction (75.3+/-4.4 Hz) and elbow flexion (73.9+/-3.7 Hz) although markedly similar for left and right movements of the same body part within subjects, suggesting activation of a common underlying network for gamma oscillations in the left and right motor cortex. These findings demonstrate that voluntary movements elicit high-frequency gamma oscillations in the primary motor cortex that are effector specific, and possibly reflect the activation of cortico-subcortical networks involved in the feedback control of discrete movements.     

Independent predictors of neuronal adaptation in human primary visual cortex measured with high-gamma activity

Neuronal adaptation is defined as a reduced neural response to a repeated stimulus and can be demonstrated by reduced augmentation of event-related gamma activity. Several studies reported that variance in the degree of gamma augmentation could be explained by pre-stimulus low-frequency oscillations. Here, we measured the spatio-temporal characteristics of visually-driven amplitude modulations in human primary visual cortex using intracranial electrocorticography. We determined if inter-stimulus intervals or pre-stimulus oscillations independently predicted local neuronal adaptation measured with amplitude changes of high-gamma activity at 80-150 Hz. Participants were given repetitive photic stimuli with a flash duration of 20 μs in each block; the inter-stimulus interval was set constant within each block but different (0.2, 0.5, 1.0 or 2.0 s) across blocks. Stimuli elicited augmentation of high-gamma activity in the occipital cortex at about 30 to 90 ms, and high-gamma augmentation was most prominent in the medial occipital region. High-gamma augmentation was subsequently followed by lingering beta augmentation at 20-30 Hz and high-gamma attenuation. Neuronal adaptation was demonstrated as a gradual reduction of high-gamma augmentation over trials. Multivariate analysis demonstrated that a larger number of prior stimuli, shorter inter-stimulus interval, and pre-stimulus high-gamma attenuation independently predicted a reduced high-gamma augmentation in a given trial, while pre-stimulus beta amplitude or delta phase had no significant predictive value. Association between pre-stimulus high-gamma attenuation and a reduced neural response suggests that high-gamma attenuation represents a refractory period. The local effects of pre-stimulus beta augmentation and delta phase on neuronal adaptation may be modest in primary visual cortex.     

The temporal frequency tuning of human visual cortex investigated using synthetic aperture magnetometry

Using synthetic aperture magnetometry (SAM) analyses of magnetoencephalographic (MEG) data, we investigated the variation in cortical response magnitude and frequency as a function of stimulus temporal frequency. In two separate experiments, a reversing checkerboard stimulus was used in the right or left lower visual field at frequencies from 0 to 21 Hz. Average temporal frequency tuning curves were constructed for regions-of-interest located within medial visual cortex and V5/MT. In medial visual cortex, it was found that both the frequency and magnitude of the steady-state response varied as a function of the stimulus frequency, with multiple harmonics of the stimulus frequency being found in the response. The maximum fundamental response was found at a stimulus frequency of 8 Hz, whilst the maximum broadband response occurred at 4 Hz. In contrast, the magnitude and frequency content of the evoked onset response showed no dependency on stimulus frequency. Whilst medial visual cortex showed a power increase during stimulation, extra-striate areas such as V5/MT exhibited a bilateral event-related desynchronisation (ERD). The frequency content of this ERD did not depend on the stimulus frequency but was a broadband power reduction across the 5-20 Hz frequency range. The magnitude of this ERD within V5/MT was strongly low-pass tuned for stimulus frequency, and showed only a moderate preference for stimuli in the contralateral visual field.     

Syntactic and auditory spatial processing in the human temporal cortex: an MEG study

Processing syntax is believed to be a higher cognitive function involving cortical regions outside sensory cortices. In particular, previous studies revealed that early syntactic processes at around 100-200 ms affect brain activations in anterior regions of the superior temporal gyrus (STG), while independent studies showed that pure auditory perceptual processing is related to sensory cortex activations. However, syntax-related modulations of sensory cortices were reported recently, thereby adding diverging findings to the previous studies. The goal of the present magnetoencephalography study was to localize the cortical regions underlying early syntactic processes and those underlying perceptual processes using a within-subject design. Sentences varying the factors syntax (correct vs. incorrect) and auditory space (standard vs. change of interaural time difference (ITD)) were auditorily presented. Both syntactic and auditory spatial anomalies led to very early activations (40-90 ms) in the STG. Around 135 ms after violation onset, differential effects were observed for syntax and auditory space, with syntactically incorrect sentences leading to activations in the anterior STG, whereas ITD changes elicited activations more posterior in the STG. Furthermore, our observations strongly indicate that the anterior and the posterior STG are activated simultaneously when a double violation is encountered. Thus, the present findings provide evidence of a dissociation of speech-related processes in the anterior STG and the processing of auditory spatial information in the posterior STG, compatible with the view of different processing streams in the temporal cortex.     

A spatial and temporal comparison of hemodynamic signals measured using optical and functional magnetic resonance imaging during activation in the human primary visual cortex

Functional near infrared spectro-imaging (fNIRSI) is potentially a very useful technique for obtaining information about the underlying physiology of the blood oxygenation level dependent (BOLD) signal used in functional magnetic resonance imaging (fMRI). In this paper the temporal and spatial statistical characteristics of fNIRSI data are compared to those of simultaneously acquired fMRI data in the human visual cortex during a variable-frequency reversing checkerboard activation paradigm. Changes in the size of activated volume caused by changes in checkerboard reversal frequency allowed a comparison of the behavior of the spatial responses measured by the two imaging methods. fNIRSI and fMRI data were each analyzed using standard correlation and fixed-effect group analyses of variance pathways. The statistical significance of fNIRSI data was found to be much lower than that of the fMRI data, due mainly to the low signal-to-noise of the measurements. Reconstructed images also showed that, while the time-course of changes in the oxy-, deoxy-, and total hemoglobin concentrations all exhibit high correlation with that of the BOLD response, the changes in the volume of tissue measured as "activated" by the BOLD response demonstrate a closer similarity to the corresponding changes in the oxy- and total hemoglobin concentrations than to that of the deoxyhemoglobin.     

正常老化对视皮层静息状态脑活动的影响

目的利用fMRI技术初步探讨年龄对人类视皮层静息状态活动的影响。方法10名健康青年志愿者及10名老年健康志愿者参加实验。任务通过听觉呈现。任务期要求受试者听汉语真词词组并作词语属性判断(具体或抽象)。静息期要求受试者闭眼、静卧,不做任何主动思维活动。利用SPM 2软件进行数据处理,采用反减法获得负激活图。结果两组受试者负激活脑区部位基本一致,主要包括扣带回后部/楔前叶(BA 7),前额叶中内侧(BA 32/10),两侧前额叶背外侧(BA 9),两侧顶下小叶(BA 39/40),两侧枕叶视皮层(BA 18/19),左侧基底节区及两侧岛叶(BA 13)。该负激活脑区模式与Raichle等提出的脑默认活动网络基本一致。进一步组间分析发现,老年人视皮层静息期fMR信号强度明显高于青年人组。结论本研究进一步验证了静息状态人脑默认活动假说,并发现静息状态时老年人视皮层活动比青年人活跃。     

High gamma frequency oscillatory activity dissociates attention from intention in the human premotor cortex

The premotor cortex is well known for its role in motor planning. In addition, recent studies have shown that it is also involved in nonmotor functions such as attention and memory, a notion derived from both animal neurophysiology and human functional imaging. The present study is an attempt to bridge the gap between these experimental techniques in the human brain, using a task initially designed to dissociate attention from intention in the monkey, and recently adapted for a functional magnetic resonance imaging (fMRI) study [Simon, S.R., Meunier, M., Piettre, L., Berardi, A.M., Segebarth, C.M., Boussaoud, D. (2002). Spatial attention and memory versus motor preparation: premotor cortex involvement as revealed by fMRI. J. Neurophysiol., 88, 2047-57]. Intracranial EEG was recorded from the cortical regions preferentially active in the spatial attention and/or working memory task and those involved in motor intention. The results show that, among the different intracranial EEG responses, only the high gamma frequency (60-200 Hz) oscillatory activity both dissociates attention/memory from motor intention and spatially colocalizes with the fMRI-identified premotor substrates of these two functions. This finding provides electrophysiological confirmation that the human premotor cortex is involved in spatial attention and/or working memory. Additionally, it provides timely support to the idea that high gamma frequency oscillations are involved in the cascade of neural processes underlying the hemodynamic responses measured with fMRI [Logothetis, N.K., Pauls, J., Augath, M., Trinath, T. and Oeltermann, A. (2001). Neurophysiological investigation of the basis of the fMRI signal. Nature, 412, 150-7], and suggests a functional selectivity of the gamma oscillations that could be critical for future EEG investigations, whether experimental or clinical.     

Hemispheric specialization of human inferior temporal cortex during coarse-to-fine and fine-to-coarse analysis of natural visual scenes

Recent models of visual recognition have suggested that perceptual analysis may start with a parallel extraction of different spatial frequencies (SF), using a preferential coarse-to-fine (low-to-high SF) sequence of processing. A rapid extraction of low spatial frequency (LSF) information may thus provide an initial and crude parsing of the visual scene, subsequently refined by slow but more detailed high spatial frequency (HSF) information. However, the sequence of SF analysis could be flexible, a high-to-low (HtL) being sometimes preferred to a low-to-high (LtH) SF sequence depending on task demands. Furthermore, it has also been suggested that the right vs. left hemisphere might be differentially specialized in LSF vs. HSF analysis, respectively. By manipulating the temporal succession of LSF and HSF stimuli, the present fMRI study investigated whether such hemispheric specialization may underlie the flexible use of different time-course in SF analysis. Participants performed a matching task between two successive images of natural scenes (LSF or HSF) that were displayed either in an LtH (LSF scene presented first and HSF scene second) or in a reverse HtL sequence. A direct inter-hemispheric comparison of the neural responses evoked by each SF sequence revealed greater activations within the right occipito-temporal cortex for the LtH sequence and within the left occipito-temporal cortex for the HtL sequence. These fMRI results suggest that the hemisphere preferentially engaged during the sequential processing of different SF might be determined by the initial SF-band appearing in this sequence, and that both a coarse-to-fine and fine-to-coarse analysis might independently take place in the two hemispheres.     

Population receptive field estimates in human visual cortex

We introduce functional MRI methods for estimating the neuronal population receptive field (pRF). These methods build on conventional visual field mapping that measures responses to ring and wedge patterns shown at a series of visual field locations and estimates the single position in the visual field that produces the largest response. The new method computes a model of the population receptive field from responses to a wide range of stimuli and estimates the visual field map as well as other neuronal population properties, such as receptive field size and laterality. The visual field maps obtained with the pRF method are more accurate than those obtained using conventional visual field mapping, and we trace with high precision the visual field maps to the center of the foveal representation. We report quantitative estimates of pRF size in medial, lateral and ventral occipital regions of human visual cortex. Also, we quantify the amount of input from ipsi- and contralateral visual fields. The human pRF size estimates in V1-V3 agree well with electrophysiological receptive field measurements at a range of eccentricities in corresponding locations within monkey and human visual field maps. The pRF method is non-invasive and can be applied to a wide range of conditions when it is useful to link fMRI signals in the visual pathways to neuronal receptive fields.     

Spatiotemporal characteristics of form analysis in the human visual cortex revealed by rapid event-related fMRI adaptation

The integration of local elements to coherent forms is at the core of understanding visual perception. Accumulating evidence suggests that both early retinotopic and higher occipitotemporal areas contribute to the integration of local elements to global forms. However, the spatiotemporal characteristics of form analysis in the human visual cortex remain largely unknown. The aim of this study was to investigate form analysis at different spatial (global vs. local structure) and temporal (different stimulus presentation rates) scales across stages of visual analysis (from V1 to the lateral occipital complex-LOC) in the human brain. We used closed contours rendered by Gabor elements and manipulated either the global contour structure or the orientation of the local Gabor elements. Our rapid event-related fMRI adaptation studies suggest that contour integration and form processing in early visual areas is transient and limited within the local neighborhood of their cells' receptive field. In contrast, higher visual areas appear to process the perceived global form in a more sustained manner. Finally, we demonstrate that these spatiotemporal properties of form processing in the visual cortex are modulated by attention. Attention to the global form maintains sustained processing in occipitotemporal areas, whereas attention to local elements enhances their integration in early visual areas. These findings provide novel neuroimaging evidence for form analysis at different spatiotemporal scales across human visual areas and validate the use of rapid event-related fMRI adaptation for investigating processing across stages of visual analysis in the human brain.     

Consistent and precise localization of brain activity in human primary visual cortex by MEG and fMRI

The tomographic localization of activity within human primary visual cortex (striate cortex or V1) was examined using whole-head magnetoencephalography (MEG) and 4-T functional magnetic resonance imaging (fMRI) in four subjects. Circular checkerboard pattern stimuli with radii from 1.8 to 5.2 degrees were presented at eccentricity of 8 degrees and angular position of 45 degrees in the lower quadrant of the visual field to excite the dorsal part of V1 which is distant from the V1/V2 border and from the fundus of the calcarine sulcus. Both fMRI and MEG identified spatially well-overlapped activity within the targeted area in each subject. For MEG, in three subjects a very precise activation in V1 was identified at 42 ms for at least one of the two larger stimulus sizes (radii 4.5 and 5.2 degrees ). When this V1 activity was present, it marked the beginning of a weak wave of excitations in striate and extrastriate areas which ended at 50 ms (M50). The beginning of the next wave of activations (M70) was also marked by a brief V1 activation, mainly between 50 and 60 ms. The mean separation between V1 activation centers identified by fMRI and the earliest MEG activation was 3-5 mm.     

Automatic volumetric segmentation of human visual retinotopic cortex

Previous identification of early visual cortical areas in humans with phase-encoded retinotopic mapping techniques have relied on an accurate cortical surface reconstruction. Here a 3D phase-encoded retinotopic mapping technique that does not require a reconstruction of the cortical surface is demonstrated. The visual field sign identification is completely automatic and the method directly supplies volumes for a region-of-interest analysis, facilitating the application of cortical mapping to a wider population. A validation of the method is provided by simulations and comparison to cortical surface-based methodology.     

年老化视觉空间注意等级效应脑机制的研究

目的：应用“提示-目标”的视觉实验范式，以汉字提示不同等级的搜索范围并设置干扰，通过事件相关电位技术研究视觉注意年老化脑机制。方法：用青年和老年人各16名为受试对象，背景由三个同心圆组成，提示为汉字“大”、“中”、“小”，刺激材料是随机选取的大写英文字母，组成3个同心圆圈。“T”为靶刺激，“T”不是唯一的，受试对象按照提示搜索提示范围上的靶刺激，忽略其它范围里的“T”。结果：随着提示等级的减小，两组反应时均加快，而早期ERP成分P1与N1波幅均增大，与青年组相比，老年组反应时更长，且后部P1显著增强和N1明显抑制，老年组前部P2成分亦受到显著抑制，这种抑制不仅表现在波幅上，还表现在波形的不规则和不稳定。结论：老年受试对象随任务的复杂度增加需要消耗更多的资源，与年老化的“复杂度效应”一致。老年组P2成分的显著抑制为首次发现，表明老年组受试对象对靶刺激的评估识别能力降低，提示年老化可能导致视觉空问注意的前脑区功能缺陷。     

Spatiotemporal frequency tuning of BOLD and gamma band MEG responses compared in primary visual cortex

In this study, the spatial and temporal frequency tuning characteristics of the MEG gamma (40-60 Hz) rhythm and the BOLD response in primary visual cortex were measured and compared. In an identical MEG/fMRI paradigm, 10 participants viewed reversing square wave gratings at 2 spatial frequencies [0.5 and 3 cycles per degree (cpd)] reversing at 5 temporal frequencies (0, 1 6, 10, 15 Hz). Three-dimensional images of MEG source power were generated with synthetic aperture magnetometry (SAM) and showed a high degree of spatial correspondence with BOLD responses in primary visual cortex with a mean spatial separation of 6.5 mm, but the two modalities showed different tuning characteristics. The gamma rhythm showed a clear increase in induced power for the high spatial frequency stimulus while BOLD showed no difference in activity for the two spatial frequencies used. Both imaging modalities showed a general increase of activity with temporal frequency, however, BOLD plateaued around 6-10 Hz while the MEG generally increased with a dip exhibited at 6 Hz. These results demonstrate that the two modalities may show activation in similar spatial locations but that the functional pattern of these activations may differ in a complex manner, suggesting that they may be tuned to different aspects of neuronal activity.     

CpG DNA and LPS induce distinct patterns of activation in human monocytes.

A specific set of immune functions is switched on in response to DNA containing unmethylated CpG dinucleotides in particular base contexts ('CpG motifs'). Plasmids, viral vectors and antisense oligodeoxynucleotides used for DNA vaccination, gene replacement or gene blockade contain immunostimulatory CpG motifs which may have independent biological activity. Although the immune stimulatory effects of CpG motifs on murine cells are well established, the evaluation of their possible effects on human cells is complicated by the higher LPS sensitivity of human leukocytes compared with those in mice. To address this issue, we analyzed CpG- and LPS-mediated immune activation of human PBMC. The biologic activity of LPS could be detected within 4 h using intracellular TNF staining of monocytes with flow cytometry at concentrations just one-twentieth (0.0014 Eu/ml) of the lower detection limit for the routinely used LAL assay (0.03 EU/ml). In contrast to the rapid LPS response, CpG DNA-stimulated TNF and IL-6 synthesis in human monocytes was not detectable until 18 h. E. coli DNA induced IL-6 synthesis in a concentration-dependent manner (30 micrograms/ml E. coli DNA; 409 pg/ml +/- 75 pg/ml, n = 7, IL-6 ELISA), but calf thymus DNA did not (< 10 pg/ml). Likewise, the CpG oligodeoxynucleotides 1760 (phosphorothioate) and 2059 (unmodified) induced IL-6 synthesis, but the corresponding control oligonucleotides 1908 and 2077 did not CpG DNA and LPS enhanced IL-6 synthesis synergistically. ICAM-1-expression of monocytes was increased 4.6-fold by E. coli DNA, 3.5-fold by 1760 and three-fold by 2059, compared with 3.6-fold by a maximal LPS stimulus and no change with non-CpG DNA. In conclusion, CpG-motifs induce TNF, IL-6 and ICAM-1 expression in human monocytes, but the kinetics of this differ from that induced by LPS, which makes it possible to distinguish immune activation by these agents. These results have important implications for the clinical development of therapeutic DNA in humans.     

Two distinct neural effects of blinking on human visual processing

Humans blink every few seconds, yet the changes in retinal illumination during a blink are rarely noticed, perhaps because visual sensitivity is suppressed. Furthermore, despite the loss of visual input, visual experience remains continuous across blinks. The neural mechanisms in humans underlying these two phenomena of blink suppression and visual continuity are unknown. We investigated the neural basis of these two complementary behavioural effects using functional magnetic resonance imaging to measure how voluntary blinking affected cortical responses to visual stimulation. Two factors were independently manipulated in a blocked design; the presence/absence of voluntary blinking, and the presence/absence of visual stimulation. To control for the simple loss of visual input caused by eyelid closure, we created a fifth condition where external darkenings were dynamically matched to each subjects' own blinks. Areas of lateral occipital cortex, including area V5/MT, showed suppression of responses to visual stimulation during blinking, consistent with the known loss in visual sensitivity. In contrast, a medial parieto-occipital region, homologous to macaque area V6A, showed responses to blinks that increased when visual stimulation was present. Our data are consistent with a role for this region in the active maintenance of visual continuity across blinks. Moreover, both suppression in lateral occipital and activation in medial parieto-occipital cortex were greater during blinks than during matched external darkenings of the visual scene, suggesting that they result from an extra-retinal signal associated with the blink motor command. Our findings therefore suggest two distinct neural correlates of blinking on human visual processing.     

Locating the initial stages of speech-sound processing in human temporal cortex

It is commonly assumed that, in the cochlea and the brainstem, the auditory system processes speech sounds without differentiating them from any other sounds. At some stage, however, it must treat speech sounds and nonspeech sounds differently, since we perceive them as different. The purpose of this study was to delimit the first location in the auditory pathway that makes this distinction using functional MRI, by identifying regions that are differentially sensitive to the internal structure of speech sounds as opposed to closely matched control sounds. We analyzed data from nine right-handed volunteers who were scanned while listening to natural and synthetic vowels, or to nonspeech stimuli matched to the vowel sounds in terms of their long-term energy and both their spectral and temporal profiles. The vowels produced more activation than nonspeech sounds in a bilateral region of the superior temporal sulcus, lateral and inferior to regions of auditory cortex that were activated by both vowels and nonspeech stimuli. The results suggest that the perception of vowel sounds is compatible with a hierarchical model of primate auditory processing in which early cortical stages of processing respond indiscriminately to speech and nonspeech sounds, and only higher regions, beyond anatomically defined auditory cortex, show selectivity for speech sounds.