首发精神分裂症患者听感觉门控P50及认知功能的相关性研究

目的 探讨首发精神分裂症患者听感觉门控P50与威斯康星卡片分类测验之间的相关性.方法 采用配对听觉条件、测试刺激范式及威斯康星卡片分类测验对51名首发精神分裂症患者和51名健康常人进行检测,并进行相关性分析.结果 患者组听感觉门控P50抑制明显高于对照组(P<0.01);威斯康星卡片分类测验结果显示,患者组完成分类数和正确分类数显著低于对照组,而错误数和持续错误数显著高于对照组(P<0.01);患者组听感觉门控P50抑制与威斯康星卡片分类测验指标间无相关性.结论 首发精神分裂症患者存在认知功能损害与额叶功能缺陷,反映出可能存在不同的神经发生机制.     

Evidence for a frontal cortex role in both auditory and somatosensory habituation: a MEG study

Auditory and somatosensory responses to paired stimuli were investigated for commonality of frontal activation that may be associated with gating using magnetoencephalography (MEG). A paired stimulus paradigm for each sensory evoked study tested right and left hemispheres independently in ten normal controls. MR-FOCUSS, a current density technique, imaged simultaneously active cortical sources. Each subject showed source localization, in the primary auditory or somatosensory cortex, for the respective stimuli following both the first (S1) and second (S2) impulses. Gating ratios for the auditory M50 response, equivalent to the P50 in EEG, were 0.54+/-0.24 and 0.63+/-0.52 for the right and left hemispheres. Somatosensory gating ratios were evaluated for early and late latencies as the pulse duration elicits extended response. Early gating ratios for right and left hemispheres were 0.69+/-0.21 and 0.69+/-0.41 while late ratios were 0.81+/-0.41 and 0.80+/-0.48. Regions of activation in the frontal cortex, beyond the primary auditory or somatosensory cortex, were mapped within 25 ms of peak S1 latencies in 9/10 subjects during auditory stimulus and in 10/10 subjects for somatosensory stimulus. Similar frontal activations were mapped within 25 ms of peak S2 latencies for 75% of auditory responses and for 100% of somatosensory responses. Comparison between modalities showed similar frontal region activations for 17/20 S1 responses and for 13/20 S2 responses. MEG offers a technique for evaluating cross modality gating. The results suggest similar frontal sources are simultaneously active during auditory and somatosensory habituation.     

Neuronal chronometry of target detection: fusion of hemodynamic and event-related potential data

Event-related potential (ERP) studies of the brain's response to infrequent, target (oddball) stimuli elicit a sequence of physiological events, the most prominent and well studied being a complex, the P300 (or P3) peaking approximately 300 ms post-stimulus for simple stimuli and slightly later for more complex stimuli. Localization of the neural generators of the human oddball response remains challenging due to the lack of a single imaging technique with good spatial and temporal resolution. Here, we use independent component analyses to fuse ERP and fMRI modalities in order to examine the dynamics of the auditory oddball response with high spatiotemporal resolution across the entire brain. Initial activations in auditory and motor planning regions are followed by auditory association cortex and motor execution regions. The P3 response is associated with brainstem, temporal lobe, and medial frontal activity and finally a late temporal lobe "evaluative" response. We show that fusing imaging modalities with different advantages can provide new information about the brain.     

Applications of the P50 evoked response to the evaluation of cognitive impairments after traumatic brain injury

This article reviews the applications of the P50 evoked response to paired auditory stimuli (P50 ERP) in the study and evaluation of cognitive impairments after traumatic brain injury (TBI). The cholinergic hypothesis of cognitive impairment after TBI and the relationship of impaired auditory sensory gating to that hypothesis are presented. The neurobiology of impaired sensory gating, the relationship of that neurobiology to the P50 ERP, and the principles of P50 ERP recording are discussed. Studies of the P50 ERP among patients with persistent cognitive complaints after TBI are reviewed. Finally, possible clinical applications and limitations of the P50 ERP in the study, evaluation, and treatment of patients with cognitive impairments after TBI are offered.     

The neural networks underlying auditory sensory gating

One of the most consistent electrophysiological deficits reported in the schizophrenia literature is the failure to inhibit, or properly gate, the neuronal response to the second stimulus of an identical pair (i.e., sensory gating). Although animal and invasive human studies have consistently implicated the auditory cortex, prefrontal cortex and hippocampus in mediating the sensory gating response, localized activation in these structures has not always been reported during non-invasive imaging modalities. In the current experiment, event-related FMRI and a variant of the traditional gating paradigm were utilized to examine how the gating network differentially responded to the processing of pairs of identical and non-identical tones. Two single-tone conditions were also presented so that they could be used to estimate the HRF for paired stimuli, reconstructed based on actual hemodynamic responses, to serve as a control non-gating condition. Results supported an emerging theory that the gating response for both paired-tone conditions was primarily mediated by auditory and prefrontal cortex, with potential contributions from the thalamus. Results also indicated that the left auditory cortex may play a preferential role in determining the stimuli that should be inhibited (gated) or receive further processing due to novelty of information. In contrast, there was no evidence of hippocampal involvement, suggesting that future work is needed to determine what role it may play in the gating response.     

Functional neuroanatomy of auditory mismatch processing: an event-related fMRI study of duration-deviant oddballs

This study was designed to identify the neural networks underlying automatic auditory deviance detection in 10 healthy subjects using functional magnetic resonance imaging. We measured blood oxygenation level-dependent contrasts derived from the comparison of blocks of stimuli presented as a series of standard tones (50 ms duration) alone versus blocks that contained rare duration-deviant tones (100 ms) that were interspersed among a series of frequent standard tones while subjects were watching a silent movie. Possible effects of scanner noise were assessed by a "no tone" condition. In line with previous positron emission tomography and EEG source modeling studies, we found temporal lobe and prefrontal cortical activation that was associated with auditory duration mismatch processing. Data were also analyzed employing an event-related hemodynamic response model, which confirmed activation in response to duration-deviant tones bilaterally in the superior temporal gyrus and prefrontally in the right inferior and middle frontal gyri. In line with previous electrophysiological reports, mismatch activation of these brain regions was significantly correlated with age. These findings suggest a close relationship of the event-related hemodynamic response pattern with the corresponding electrophysiological activity underlying the event-related "mismatch negativity" potential, a putative measure of auditory sensory memory.     

Sensory gating of auditory evoked and induced gamma band activity in intracranial recordings

Oscillatory activity in the gamma band range (30-50 Hz) and its functional relation to auditory evoked potentials (AEPs) is yet poorly understood. In the current study, we capitalized on the advantage of intracranial recordings and studied gamma band activity (GBA) in an auditory sensory gating experiment. Recordings were obtained from the lateral surface of the temporal lobe in 34 epileptic patients undergoing presurgical evaluation. Two kinds of activity were differentiated: evoked (phase locked) and induced (not phase locked) GBA. In 18 patients, an intracranial P50 was observed. At electrodes with maximal P50, evoked GBA occurred with a similar peak latency as the P50. However, the intensities of P50 and evoked GBA were only modestly correlated, suggesting that the intracranial P50 does not represent a subset of evoked GBA. The peak frequency of the intracranial evoked GBA was on average relatively low (approximately 25 Hz) and is, therefore, probably not equivalent to extracranially recorded GBA which has normally a peak frequency of approximately 40 Hz. Induced GBA was detected in 10 subjects, nearly exclusively in the region of the superior temporal lobe. The induced GBA was increased after stimulation for several hundred milliseconds and encompassed frequencies up to 200 Hz. Single-trial analysis revealed that induced GBA occurred in relatively short bursts (mostly <100 ms), indicating that the duration of the induced GBA in the averages originates from summation effects. Both types of gamma band activity showed a clear attenuation with stimulus repetition.     

Spatiotemporal signatures of an abnormal auditory system in stuttering

People who stutter (PWS) can reduce their stuttering rates under masking noise and altered auditory feedback; such a response can be attributed to altered auditory input, which suggests that abnormal speech processing in PWS results from abnormal processing of auditory input. However, the details of this abnormal processing of basic auditory information remain unclear. In order to characterize such abnormalities, we examined the functional and structural changes in the auditory cortices of PWS by using a 306-channel magnetoencephalography system to assess auditory sensory gating (P50m suppression) and tonotopic organization. Additionally, we employed voxel-based morphometry to compare cortical gray matter (GM) volumes on structural MR images. PWS exhibited impaired left auditory sensory gating. The tonotopic organization in the right hemisphere of PWS is expanded compared with that of the controls. Furthermore, PWS showed a significant increase in the GM volume of the right superior temporal gyrus, consistent with the right tonotopic expansion. Accordingly, we suggest that PWS have impaired left auditory sensory gating during basic auditory input processing and that some error signals in the auditory cortex could result in abnormal speech processing. Functional and structural reorganization of the right auditory cortex appears to be a compensatory mechanism for impaired left auditory cortex function in PWS.     

Detection of audio-visual integration sites in humans by application of electrophysiological criteria to the BOLD effect

Electrophysiological studies in nonhuman primates and other mammals have shown that sensory cues from different modalities that appear at the same time and in the same location can increase the firing rate of multisensory cells in the superior colliculus to a level exceeding that predicted by summing the responses to the unimodal inputs. In contrast, spatially disparate multisensory cues can induce a profound response depression. We have previously demonstrated using functional magnetic resonance imaging (fMRI) that similar indices of crossmodal facilitation and inhibition are detectable in human cortex when subjects listen to speech while viewing visually congruent and incongruent lip and mouth movements. Here, we have used fMRI to investigate whether similar BOLD signal changes are observable during the crossmodal integration of nonspeech auditory and visual stimuli, matched or mismatched solely on the basis of their temporal synchrony, and if so, whether these crossmodal effects occur in similar brain areas as those identified during the integration of audio-visual speech. Subjects were exposed to synchronous and asynchronous auditory (white noise bursts) and visual (B/W alternating checkerboard) stimuli and to each modality in isolation. Synchronous and asynchronous bimodal inputs produced superadditive BOLD response enhancement and response depression across a large network of polysensory areas. The most highly significant of these crossmodal gains and decrements were observed in the superior colliculi. Other regions exhibiting these crossmodal interactions included cortex within the superior temporal sulcus, intraparietal sulcus, insula, and several foci in the frontal lobe, including within the superior and ventromedial frontal gyri. These data demonstrate the efficacy of using an analytic approach informed by electrophysiology to identify multisensory integration sites in humans and suggest that the particular network of brain areas implicated in these crossmodal integrative processes are dependent on the nature of the correspondence between the different sensory inputs (e.g. space, time, and/or form).     

Frontal lobe involvement in the processing of meaningful auditory stimuli develops during childhood and adolescence

Auditory event-related N1b reflects attention-related processing in bilateral temporal auditory cortex. Frontal contributions indicating an orienting reaction have been suggested. We analyzed the maturation of frontal contributions to the auditory event-related potential following the warning stimulus in a contingent negative variation (CNV) task by high-resolution current source density mapping and spatio-temporal source analysis in 80 healthy subjects and 121 primary headache patients (migraine with/without aura, tension type headache) from 6 to 18 years; as increased orienting responses and disturbed maturation have been described in migraineurs. A selective local increase of N1b with age occurred at mid-frontocentral leads. This increase could not be explained sufficiently by overlapping bilateral temporal sources but pointed towards additional frontal activation over the supplementary motor area (SMA) in adolescents which was absent in children. A second frontal N1 component peaked about 50 ms later, showed an earlier maturation and has been suggested to reflect early response selection processes in the anterior cingulate. Primary headache patients showed the same component structure and developmental trajectory as healthy subjects without significant influences of differential diagnosis. We conclude that: (1) Brain maturation crucially influences N1b. (2) Two frontal lobe N1 components can be dissociated in their maturational trajectory. (3) Early SMA activation could be elicited by rare auditory stimuli from about 12 years on, allowing fast sensory-motor coupling without previous categorical stimulus classification. (4) Primary headache patients did not differ in their maturation of frontal or temporal contributions to N1b when elicited by moderately loud short tone bursts.     

Source localization of sensory gating: a combined EEG and fMRI study in healthy volunteers

Reduced sensory gating appears to be among the core features in schizophrenia. The sources of sensory gating however are largely unknown. The aim of the current study was to identify these sources, with concurrent EEG and fMRI methodology. Twenty healthy male volunteers were tested with identical P50 suppression paradigms in two separate sessions: an EEG setting, and an EEG concurrent with fMRI setting. The stimuli in the P50 paradigm consisted of weak electrical stimulation of the left median nerve. The stimuli were presented in pairs with either 500 ms or 1000 ms interstimulus intervals (ISI). No difference was found between the EEG setting and the concurrent EEG and fMRI setting. P50 suppression was, in both settings, found only in the 500 ms trials, not in the 1000 ms trials. EEG-dipole modeling resulted in 4 sources located in the medial frontal gyrus, the insula, the hippocampus, and primary somatosensory cortex. These sources corresponded to significant fMRI clusters located in the medial frontal gyrus, the insula, the claustrum, and the hippocampus. Activity in the hippocampus and the claustrum was higher in the trials with suppression, suggesting that these brain areas are involved in the inhibitory processes of P50 suppression. The opposite was found for activity in the medial frontal gyrus and the insula, suggesting that these brain areas are involved in the generation of the P50 amplitude. To our knowledge, this is the first study demonstrating that P50 suppression can be reliably assessed inside an MRI scanner.     

Motor speech perception modulates the cortical language areas

Traditionally, the left frontal and parietal lobes have been associated with language production while regions in the temporal lobe are seen as crucial for language comprehension. However, recent evidence suggests that the classical language areas constitute an integrated network where each area plays a crucial role both in speech production and perception. We used functional MRI to examine whether observing speech motor movements (without auditory speech) relative to non-speech motor movements preferentially activates the cortical speech areas. Furthermore, we tested whether the activation in these regions was modulated by task difficulty. This dissociates between areas that are actively involved with speech perception from regions that show an obligatory activation in response to speech movements (e.g. areas that automatically activate in preparation for a motoric response). Specifically, we hypothesized that regions involved with decoding oral speech would show increasing activation with increasing difficulty. We found that speech movements preferentially activate the frontal and temporal language areas. In contrast, non-speech movements preferentially activate the parietal region. Degraded speech stimuli increased both frontal and parietal lobe activity but did not differentially excite the temporal region. These findings suggest that the frontal language area plays a role in visual speech perception and highlight the differential roles of the classical speech and language areas in processing others' motor speech movements.     

Enhanced EEG gamma-band activity reflects multisensory semantic matching in visual-to-auditory object priming

An important step in perceptual processing is the integration of information from different sensory modalities into a coherent percept. It has been suggested that such crossmodal binding might be achieved by transient synchronization of neurons from different modalities in the gamma-frequency range (> 30 Hz). Here we employed a crossmodal priming paradigm, modulating the semantic congruency between visual–auditory natural object stimulus pairs, during the recording of the high density electroencephalogram (EEG). Subjects performed a semantic categorization task. Analysis of the behavioral data showed a crossmodal priming effect (facilitated auditory object recognition) in response to semantically congruent stimuli. Differences in event-related potentials (ERP) were found between 250 and 350 ms, which were localized to left middle temporal gyrus (BA 21) using a distributed linear source model. Early gamma-band activity (40–50 Hz) was increased between 120 ms and 180 ms following auditory stimulus onset for semantically congruent stimulus pairs. Source reconstruction for this gamma-band response revealed a maximal increase in left middle temporal gyrus (BA 21), an area known to be related to the processing of both complex auditory stimuli and multisensory processing. The data support the hypothesis that oscillatory activity in the gamma-band reflects crossmodal semantic-matching processes in multisensory convergence sites.     

Sensory gating and source analysis of the auditory P50 in low and high suppressors

Impairments in sensory gating in schizophrenia have been reflected by diminished suppression of the scalp-recorded middle latency auditory P50 event-related potential (MLAERP) elicited by the second (S₂) of a pair (S₁–S₂) of clicks. As understanding the functional neural substrates of aberrant gating would have important implications for schizophrenia, this study examined the location and time-course of the neural generators of the P50 MLAERP and its gating on subgroups of healthy volunteers exhibiting low (n = 12) and high (n = 12) P50 suppression. Suppressor differences were observed with S₁ P50 (high > low) and S₂ P50 (high < low) amplitudes, and current source density analysis with standardized Low Resolution Electromagnetic Tomography (sLORETA) evidenced an S₁ P50-related activation of limbic, temporal and parietal regions in the high but not the low suppressors. Distributed source localization of the Gating Difference Wave (GDW), obtained by subtracting the S₂ P50 response from the S₁ P50 response, also revealed a later and sustained frontal activation to characterize high suppressors. These findings suggest that impaired gating of the kind evident in schizophrenia may involve the deficient functioning of multiple interconnected and temporally overlapping activated brain regions.     

Attentional and linguistic interactions in speech perception

The role of attention in speech comprehension is not well understood. We used fMRI to study the neural correlates of auditory word, pseudoword, and nonspeech (spectrally rotated speech) perception during a bimodal (auditory, visual) selective attention task. In three conditions, Attend Auditory (ignore visual), Ignore Auditory (attend visual), and Visual (no auditory stimulation), 28 subjects performed a one-back matching task in the assigned attended modality. The visual task, attending to rapidly presented Japanese characters, was designed to be highly demanding in order to prevent attention to the simultaneously presented auditory stimuli. Regardless of stimulus type, attention to the auditory channel enhanced activation by the auditory stimuli (Attend Auditory>Ignore Auditory) in bilateral posterior superior temporal regions and left inferior frontal cortex. Across attentional conditions, there were main effects of speech processing (word+pseudoword>rotated speech) in left orbitofrontal cortex and several posterior right hemisphere regions, though these areas also showed strong interactions with attention (larger speech effects in the Attend Auditory than in the Ignore Auditory condition) and no significant speech effects in the Ignore Auditory condition. Several other regions, including the postcentral gyri, left supramarginal gyrus, and temporal lobes bilaterally, showed similar interactions due to the presence of speech effects only in the Attend Auditory condition. Main effects of lexicality (word>pseudoword) were isolated to a small region of the left lateral prefrontal cortex. Examination of this region showed significant word>pseudoword activation only in the Attend Auditory condition. Several other brain regions, including left ventromedial frontal lobe, left dorsal prefrontal cortex, and left middle temporal gyrus, showed Attention x Lexicality interactions due to the presence of lexical activation only in the Attend Auditory condition. These results support a model in which neutral speech presented in an unattended sensory channel undergoes relatively little processing beyond the early perceptual level. Specifically, processing of phonetic and lexical-semantic information appears to be very limited in such circumstances, consistent with prior behavioral studies.     

Evaluating reverse speech as a control task with language-related gamma activity on electrocorticography

Reverse speech has often been used as a control task in brain-mapping studies of language utilizing various non-invasive modalities. The rationale is that reverse speech is comparable to forward speech in terms of auditory characteristics, while omitting the linguistic components. Thus, it may control for non-language auditory functions. This finds some support in fMRI studies indicating that reverse speech resulted in less blood-oxygen-level-dependent (BOLD) signal intensity in perisylvian regions than forward speech. We attempted to externally validate a reverse speech control task using intracranial electrocorticography (ECoG) in eight patients with intractable focal epilepsy. We studied adolescent and adult patients who underwent extraoperative ECoG prior to resective epilepsy surgery. All patients received an auditory language task during ECoG recording. Patients were presented 115 audible question stimuli, including 30 reverse speech trials. Reverse speech trials more strongly engaged bilateral superior temporal sites than did the corresponding forward speech trials. Forward speech trials elicited larger gamma-augmentation at frontal lobe sites not attributable to sensorimotor function. Other temporal and frontal sites of significant augmentation showed no significant difference between reverse and forward speech. Thus, we failed to validate reported evidence of weaker activation of temporal neocortices during reverse compared to forward speech. Superior temporal lobe engagement may indicate increased attention to reverse speech. Reverse speech does not appear to be a suitable task for the control of non-language auditory functions on ECoG.     

Functional segregation of the temporal lobes into highly differentiated subsystems for auditory perception: an auditory rapid event-related fMRI-task

With this study, we explored the blood oxygen level-dependent responses within the temporal lobe to short auditory stimuli of different classes. To address this issue, we performed an attentive listening event-related fMRI study, where subjects were required to concentrate during the presentation of different types of stimuli. Because the order of stimuli was randomized and not predictable for the subject, the observed differences between the stimuli types were interpreted as an automatic effect and were not affected by attention. We used three types of stimuli: tones, sounds of animals and instruments, and words. We found in all cases bilateral activations of the primary and secondary auditory cortex. The strength and lateralization depended on the type of stimulus. The tone trials led to the weakest and smallest activations. The perception of sounds increased the activated network bilaterally into the superior temporal sulcus mainly on the right and the perception of words led to the highest activation within the left superior temporal sulcus as well as in left inferior frontal gyrus. Within the left temporal sulcus, we were able to distinguish between different subsystems, showing an extending activation from posterior to anterior for speech and speechlike information. Whereas posterior parts were involved in analyzing the complex auditory structure of sounds and speech, the middle and anterior parts responded strongest only in the perception of speech. In summary, a functional segregation of the temporal lobes into several subsystems responsible for auditory processing was visible. A lateralization for verbal stimuli to the left and sounds to the right was already detectable when short stimuli were used.     

fMRI during natural sleep as a method to study brain function during early childhood

Many techniques to study early functional brain development lack the whole-brain spatial resolution that is available with fMRI. We utilized a relatively novel method in which fMRI data were collected from children during natural sleep. Stimulus-evoked responses to auditory and visual stimuli as well as stimulus-independent functional networks were examined in typically developing 2-4-year-old children. Reliable fMRI data were collected from 13 children during presentation of auditory stimuli (tones, vocal sounds, and nonvocal sounds) in a block design. Twelve children were presented with visual flashing lights at 2.5 Hz. When analyses combined all three types of auditory stimulus conditions as compared to rest, activation included bilateral superior temporal gyri/sulci (STG/S) and right cerebellum. Direct comparisons between conditions revealed significantly greater responses to nonvocal sounds and tones than to vocal sounds in a number of brain regions including superior temporal gyrus/sulcus, medial frontal cortex and right lateral cerebellum. The response to visual stimuli was localized to occipital cortex. Furthermore, stimulus-independent functional connectivity MRI analyses (fcMRI) revealed functional connectivity between STG and other temporal regions (including contralateral STG) and medial and lateral prefrontal regions. Functional connectivity with an occipital seed was localized to occipital and parietal cortex. In sum, 2-4 year olds showed a differential fMRI response both between stimulus modalities and between stimuli in the auditory modality. Furthermore, superior temporal regions showed functional connectivity with numerous higher-order regions during sleep. We conclude that the use of sleep fMRI may be a valuable tool for examining functional brain organization in young children.     

磁源性影像在癫痫患者术前听觉性语言区定位中的应用

目的 探讨磁源性影像在癫痫患者术前语言区定位中的应用.方法 应用磁源性影像技术对24例癫痫患者手术前行癫痫灶定位及听觉性语言区定位,并确定癫痫灶与听觉性语言区的关系.结果 24例患者中,听觉性语言中枢位于左颞叶14例,右颞叶5例,双侧颞叶5例.癫痫灶位于左颞叶14例,左颞顶叶1例,右颞叶4例,右颞顶叶1例,左额颞叶1例,右额颞顶叶1例,双侧颞叶2例.10例癫痫灶与听觉性语言中枢重叠,10例癫痫灶与听觉性语言中枢所在位置不重叠,3例癫痫灶位于语言区前方,1例癫痫灶位于语言区后方.1例患者因左颞叶胚胎发育不良性神经上皮瘤与听觉性语言区重叠未能全部切除,术后出现短期语言功能障碍,术后随访仍偶有幻听,其余患者均无语言功能障碍发生.结论 磁源性影像可对癫痫患者进行癫痫灶定位及语言区定位,对减少手术后语言功能障碍具有重要意义.     

首发精神分裂症听觉感觉门控异常的功能磁共振研究

目的通过功能磁共振成像(fMRI)技术探讨首发精神分裂症听觉感觉门控异常与脑功能异常激活之间的关系,为该病的临床研究提供更多客观依据。方法选择2011年6月至2012年6月精神科收治的15例首发精神分裂症患者作为研究组,同时选取年龄、性别、受教育程度相匹配的15例志愿者作为正常对照组,两组均进行脑功能磁共振成像,采用多声音刺激和单声音刺激比较的范式,比较两组患者感觉听觉门控的异常。结果研究组听觉感觉门控脑激活在右侧海马、右侧丘脑区明显低于正常对照组,差异有统计学意义(P<0.05)。结论首发精神分裂症患者的听觉门控异常可能与大脑海马、丘脑等功能激活异常有关。