Watching where you look: modulation of visual processing of foveal stimuli by spatial attention

Two experiments investigated the effect of sustained selective spatial attention upon the perceptual analysis of stimuli within the center of gaze. Spatial attention has typically been studied in relation to peripheral stimuli, and its relevance to the processing of central stimuli has remained relatively ignored. Here, behavioral measures in normal human volunteer participants showed that focused spatial attention can also influence responses to central stimuli, over and beyond the advantage conferred by their foveation. Event-related potentials (ERPs) showed that the action of attention upon foveal stimuli included the modulation of perceptual processing in extrastriate visual areas. Surprisingly, the visual modulation revealed an intriguing and consistent pattern of hemispheric asymmetry, in both experiments. These findings show that in addition to the established right hemisphere dominance of the brain areas that direct attention, the consequences of directed attention may also be asymmetrical.     

Impaired early visual response modulations to spatial information in chronic schizophrenia

Early visual processing stages have been demonstrated to be impaired in schizophrenia patients and their first-degree relatives. The amplitude and topography of the P1 component of the visual evoked potential (VEP) are both affected; the latter of which indicates alterations in active brain networks between populations. At least two issues remain unresolved. First, the specificity of this deficit (and suitability as an endophenotype) has yet to be established, with evidence for impaired P1 responses in other clinical populations. Second, it remains unknown whether schizophrenia patients exhibit intact functional modulation of the P1 VEP component; an aspect that may assist in distinguishing effects specific to schizophrenia. We applied electrical neuroimaging analyses to VEPs from chronic schizophrenia patients and healthy controls in response to variation in the parafoveal spatial extent of stimuli. Healthy controls demonstrated robust modulation of the VEP strength and topography as a function of the spatial extent of stimuli during the P1 component. By contrast, no such modulations were evident at early latencies in the responses from patients with schizophrenia. Source estimations localized these deficits to the left precuneus and medial inferior parietal cortex. These findings provide insights on potential underlying low-level impairments in schizophrenia.     

ERP abnormalities during semantic processing in schizophrenia

To examine the neurophysiological and cognitive characteristics of thought disturbance in schizophrenic patients, we examined the amplitude, latency, and topography of a specific event-related brain potential (ERP), the N400, which is elicited by semantically incongruent words and phrases. Twelve chronic schizophrenic patients and twelve age-matched control subjects read sentences presented visually that had either semantically correct (e.g., ‘People pray in their local church’) or incorrect endings (e.g., ‘Every Sunday morning people pray in their local nest’). Relative to normal controls, schizophrenic patients had significantly reduced N400 amplitude and increased latency to semantically anomalous endings. Additionally, a late positive component which follows the N400 was significantly reduced in amplitude in schizophrenic patients. However, patients and controls did not differ significantly in terms of the topographical distribution of either the N400 or its late positive potential, examined at 28 electrode sites. Thus, N400 topography in schizophrenic patients was not accompanied by the asymmetry which frequently characterizes the well known auditory P300 disturbance in schizophrenic patients. We concluded that these findings may reflect a profound disturbance in attentional processes in chronic schizophrenia.     

Attentional orienting triggered by gaze in schizophrenia

The ability to detect the direction of another person's gaze and to shift our own attention reflexively in the same direction facilitates the sharing of attention with other people. Such sharing of attention would seem critical for the maintenance of normal social cognition. Social cognition is severely impaired in people with schizophrenia. So, we used spatial cuing paradigms to investigate reflexive (Experiment 1) and controlled (Experiment 2) attentional orienting triggered by gaze in schizophrenia. In Experiment 1, 30 patients and 24 controls detected targets appearing right or left of a central image of a head turned right, left, or straight-ahead. These gaze-cues were non-predictive. Patients, but not controls, showed a significant congruency advantage at 100 ms SOA. The congruency advantage was similar in patients and controls at 300-800 ms SOA. In Experiment 2, 20 patients and 24 controls detected targets 300-800 ms after a central gaze-cue that pointed away from the target on 80% of trials. Controls, but not patients, were able to reverse the reflexive congruency advantage at 800 ms SOA. This study provides the first evidence that people with schizophrenia show abnormally sensitive gaze-triggered reflexive orienting. Findings are discussed in light of recent neuroimaging work investigating the neural basis of social orienting and social cognition.     

Unisensory processing and multisensory integration in schizophrenia: a high-density electrical mapping study

In real-world settings, information from multiple sensory modalities is combined to form a complete, behaviorally salient percept - a process known as multisensory integration. While deficits in auditory and visual processing are often observed in schizophrenia, little is known about how multisensory integration is affected by the disorder. The present study examined auditory, visual, and combined audio-visual processing in schizophrenia patients using high-density electrical mapping. An ecologically relevant task was used to compare unisensory and multisensory evoked potentials from schizophrenia patients to potentials from healthy normal volunteers. Analysis of unisensory responses revealed a large decrease in the N100 component of the auditory-evoked potential, as well as early differences in the visual-evoked components in the schizophrenia group. Differences in early evoked responses to multisensory stimuli were also detected. Multisensory facilitation was assessed by comparing the sum of auditory and visual evoked responses to the audio-visual evoked response. Schizophrenia patients showed a significantly greater absolute magnitude response to audio-visual stimuli than to summed unisensory stimuli when compared to healthy volunteers, indicating significantly greater multisensory facilitation in the patient group. Behavioral responses also indicated increased facilitation from multisensory stimuli. The results represent the first report of increased multisensory facilitation in schizophrenia and suggest that, although unisensory deficits are present, compensatory mechanisms may exist under certain conditions that permit improved multisensory integration in individuals afflicted with the disorder.     

Temporally selective attention supports speech processing in 3- to 5-year-old children

Recent event-related potential (ERP) evidence demonstrates that adults employ temporally selective attention to preferentially process the initial portions of words in continuous speech. Doing so is an effective listening strategy since word-initial segments are highly informative. Although the development of this process remains unexplored, directing attention to word onsets may be important for speech processing in young children who would otherwise be overwhelmed by the rapidly changing acoustic signals that constitute speech. We examined the use of temporally selective attention in 3- to 5-year-old children listening to stories by comparing ERPs elicited by attention probes presented at four acoustically matched times relative to word onsets: concurrently with a word onset, 100 ms before, 100 ms after, and at random control times. By 80 ms, probes presented at and after word onsets elicited a larger negativity than probes presented before word onsets or at control times. The latency and distribution of this effect is similar to temporally and spatially selective attention effects measured in adults and, despite differences in polarity, spatially selective attention effects measured in children. These results indicate that, like adults, preschool aged children modulate temporally selective attention to preferentially process the initial portions of words in continuous speech.     

Transient inhibition of the dorsolateral prefrontal cortex disrupts attention-based modulation of tactile stimuli at early stages of somatosensory processing

Damage to the dorsolateral prefrontal cortex (DLPFC) impairs gating of irrelevant sensory information at early cortical processing stages. We investigated how transient inhibition of DLPFC impacts early event-related potentials (ERPs) arising from relevant or irrelevant vibrotactile stimuli to the fingertips. Specifically, we hypothesized that suppression of DLPFC using continuous theta burst stimulation (cTBS) would result in reduced attention-based modulation of tactile ERPs generated at early stages of cortical somatosensory processing. Participants received vibrotactile stimulation to the second and fifth digit on the left hand and reported target stimuli on one digit only (as instructed) in one of three groups following: (1) cTBS over DLPFC (40 s; 600 pulses of 3 stimuli at 50 Hz repeated at 5 Hz using 80% of resting motor threshold for abductor pollicis brevis), (2) sham stimulation, or (3) no stimulation. ERP amplitudes for the P50, N70, P100, N140 and long latency positivity (LLP) were quantified for attended and non-attended trials at C4, CP4, and CP3 electrodes. There was no effect of attention on the P50 and N70 however the P100, N140 and LLP were modulated with attention. The P100 and LLP were significantly more positive during trials where the stimuli were attended to, while the N140 was enhanced for non-attended stimuli. Comparisons between groups revealed a reduction in P100 attention-based modulation for the cTBS group versus sham and no-stimulation groups. While the P100 was clearly reduced for non-attended stimuli relative to attended stimuli in the sham and no-stimulation groups, this effect was attenuated following cTBS. The reduction in attentional modulation of the P100 following cTBS suggests that the DLPFC contributes to filtering irrelevant somatosensory information at early cortical processing stages. Notably the influence of the DLPFC in attention-based modulation was evident even within digits of the same hand. The present results support the use of cTBS as an effective means of transiently suppressing DLPFC excitability.     

Local and global auditory processing: behavioral and ERP evidence

Differential processing of local and global visual features is well established. Global precedence effects, differences in event-related potentials (ERPs) elicited when attention is focused on local versus global levels, and hemispheric specialization for local and global features all indicate that relative scale of detail is an important distinction in visual processing. Observing analogous differential processing of local and global auditory information would suggest that scale of detail is a general organizational principle of the brain. However, to date the research on auditory local and global processing has primarily focused on music perception or on the perceptual analysis of relatively higher and lower frequencies. The study described here suggests that temporal aspects of auditory stimuli better capture the local-global distinction. By combining short (40 ms) frequency modulated tones in series to create global auditory patterns (500 ms), we independently varied whether pitch increased or decreased over short time spans (local) and longer time spans (global). Accuracy and reaction time measures revealed better performance for global judgments and asymmetric interference that were modulated by amount of pitch change. ERPs recorded while participants listened to identical sounds and indicated the direction of pitch change at the local or global levels provided evidence for differential processing similar to that found in ERP studies employing hierarchical visual stimuli. ERP measures failed to provide evidence for lateralization of local and global auditory perception, but differences in distributions suggest preferential processing in more ventral and dorsal areas respectively.     

首发精神分裂症执行功能异常的心理生理机制

目的探讨首发精神分裂症患者大脑执行功能的缺陷机制。方法采用病例对照研究,选取年龄、性别、文化程度等匹配的精神分裂症患者组和对照组各30例。被试接受Go／Nogo测验,同时记录事件相关脑电位N2、P3的波幅和潜伏期及行为学数据。结果精神分裂症组Nogo反应错误数（12±9）高于对照组（8±5）,Go反应时（372±79）Ins明显长于对照组（320±63）ms,差异均有统计学意义（f分别为2．13,2．81;P〈0．05）;重复测量方差分析,发现组别的主效应（F1,58=7．13,P〈0．01）以及组别与组块之间的交互效应（F1,58=6．14,P〈0．05）均有统计学意义;精神分裂症组Fz电极Nogo-N2波幅（6．64±3．29）／LV比对照组（9．45±6．71）μV降低,Nogo-P3波幅（7．93±6．81）μV也比对照组下降（10．69±5．24）μV,差异均有统计学意义（t分别为2．06,2．89;P〈0．05）。Nogo-P3波幅在组别与组块之间的交互效应有统计学意义（F1,58=5．28,P〈0．05）。结论首发精神分裂症患者存在执行功能缺陷,反应时及Nogo-N2、P3可能可作为精神分裂症早期诊断指标。     

Dysfunction of early-stage visual processing in schizophrenia.

OBJECTIVE: Schizophrenia is associated with deficits in higher-order processing of visual information. This study evaluated the integrity of early visual processing in order to evaluate the overall pattern of visual dysfunction in schizophrenia. METHOD: Steady-state visual-evoked potential responses were recorded over the occipital cortex in patients with schizophrenia and in age- and sex-matched comparison volunteers. Visual-evoked potentials were obtained for stimuli composed of isolated squares that were modulated sinusoidally in luminance contrast, number of squares, or chromatic contrast in order to emphasize magnocellular or parvocellular visual pathway activity. RESULTS: Responses of patients to magnocellular-biased stimuli were significantly lower than those of comparison volunteers. These lower response levels were observed in conditions using both low luminance contrast and large squares that biased processing toward the magnocellular pathway. In contrast, responses to stimuli that biased processing toward the parvocellular pathway were not significantly different between schizophrenia patients and comparison volunteers. A significant interaction of group and stimulus type was observed in the condition using low luminance contrast. CONCLUSIONS: These findings suggest a dysfunction of lower-level visual pathways, which was more prominent for magnocellular than parvocellular biased stimuli. The magnocellular pathway helps in orienting toward salient stimuli. A magnocellular pathway deficit could contribute to higher-level visual cognitive deficits in schizophrenia.     

Counting in everyday life: discrimination and enumeration

Enumerating the number of items in a set accurately and quickly is a basic mathematical skill. This ability is especially crucial in the more real-life situations, where relevant items have to be discriminated from irrelevant distracters. Although much work has been done on the brain mechanisms and neural correlates of the enumeration and/or discrimination process, no agreement has been reached yet. We used event-related potentials (ERPs) to show the time course of brain activity elicited by a task that involved both enumeration and discrimination at the same time. We found that even though the two processes run to some extent in parallel, discrimination seems to take place mainly in an earlier time window (from 100 ms after the stimulus onset) than enumeration (beyond 200 ms after the stimulus onset). Moreover, electrophysiological evidence based on the N2 and P3 components make it reasonable to argue for the existence of a dichotomy between subitizing (for sets of less than four items) and counting (for sets of four and more items). Source estimation suggests that subitizing and counting, though being distinct brain processes, do recruit similar brain areas.     

The effect of non-visual working memory load on top-down modulation of visual processing

While a core function of the working memory (WM) system is the active maintenance of behaviorally relevant sensory representations, it is also critical that distracting stimuli are appropriately ignored. We used functional magnetic resonance imaging to examine the role of domain-general WM resources in the top-down attentional modulation of task-relevant and irrelevant visual representations. In our dual-task paradigm, each trial began with the auditory presentation of six random (high load) or sequentially ordered (low load) digits. Next, two relevant visual stimuli (e.g., faces), presented amongst two temporally interspersed visual distractors (e.g., scenes), were to be encoded and maintained across a 7-s delay interval, after which memory for the relevant images and digits was probed. When taxed by high load digit maintenance, participants exhibited impaired performance on the visual WM task and a selective failure to attenuate the neural processing of task-irrelevant scene stimuli. The over-processing of distractor scenes under high load was indexed by elevated encoding activity in a scene-selective region-of-interest relative to low load and passive viewing control conditions, as well as by improved long-term recognition memory for these items. In contrast, the load manipulation did not affect participants’ ability to upregulate activity in this region when scenes were task-relevant. These results highlight the critical role of domain-general WM resources in the goal-directed regulation of distractor processing. Moreover, the consequences of increased WM load in young adults closely resemble the effects of cognitive aging on distractor filtering [Gazzaley, A., Cooney, J. W., Rissman, J., & D’Esposito, M. (2005). Top-down suppression deficit underlies working memory impairment in normal aging. Nature Neuroscience 8, 1298-1300], suggesting the possibility of a common underlying mechanism.     

Age-Related Changes in Attended and Unattended P3 Latency in Normal Subjects

Event-related potentials to visual attended and unattended stimuli were studied in 37 normal subjects between the ages of 19 and 91. The components of the P3 responses to rare nontarget stimuli and rare target stimuli were measured as P3a and P3b, respectively. Both the P3a and P3b latencies were significantly and positively correlated with age. The N2 finding of age-related latency prolongation was comparable to the P3a changes with age. From the standpoint of the theory of automatic and controlled processing, these results suggest that both automatic processing, as reflected by the P3a, and attentional controlled processing, as reflected by the P3b, are impaired with normal aging.     

Attentional modulation of reward processing in the human brain

Although neural signals of reward anticipation have been studied extensively, the functional relationship between reward and attention has remained unclear: Neural signals implicated in reward processing could either reflect attentional biases towards motivationally salient stimuli, or proceed independently of attentional processes. Here, we sought to disentangle reward and attention‐related neural processes by independently modulating reward value and attentional task demands in a functional magnetic resonance imaging study in healthy human participants. During presentation of a visual reward cue that indicated whether monetary reward could be obtained in a subsequent reaction time task, participants either attended to the reward cue or performed an unrelated attention‐demanding task at two different levels of difficulty. In ventral striatum and ventral tegmental area, neural responses were modulated by reward anticipation irrespective of attentional demands, thus indicating attention‐independent processing of reward cues. By contrast, additive effects of reward and attention were observed in visual cortex. Critically, reward‐related activations in right anterior insula strongly depended on attention to the reward cue. Dynamic causal modelling revealed that the attentional modulation of reward processing in insular cortex was mediated by enhanced effective connectivity from ventral striatum to anterior insula. Our results provide evidence for distinct functional roles of the brain regions involved in the processing of reward‐indicating information: While subcortical structures signal the motivational salience of reward cues even when attention is fully engaged elsewhere, reward‐related responses in anterior insula depend on available attentional resources, likely reflecting the conscious evaluation of sensory information with respect to motivational value. Hum Brain Mapp 35:3036–3051, 2014. © 2013 Wiley Periodicals, Inc.     

精神分裂症患者事件相关电位P300改变对语词记忆能力的影响

目的探讨精神分裂症患者的语词记忆能力与认知电位之间的相互关系。方法对102例精神分裂症患者首先进行了听觉诱发电位P300测定，然后按有无P300潜伏期延长或/和波幅降低分为P300正常与异常组，再采用选择性提醒测验方法对其进行语词记忆测验。结果P300正常组30例在10次语词记忆测验中通过总例数28例，占93.3%，前6次通过的比例为56.7%；而P300异常组72例在10次语词记忆测验中通过的总例数只有43例，占59.7%，前6次通过的比例只有25%；两组之间的差异非常显著（P〈0.001）。P300异常组回忆总数、保持数、长时再现数及恒定长时再现数减少，而不恒定长时再现数、提醒总数及插入数显著增多，两组比较有显著性差异（P〈0.01）。结论P300异常的精神分裂症患者较P300正常的精神分裂症患者存在更严重的语词记忆障碍。     

Attentional modulation of visceral and somatic pain

A better understanding of the cortical processes underlying attentional modulation of visceral and somatic pain in health are essential for interpretation of future imaging studies of hypervigilance towards bodily sensations which is considered to be an aetiologically important factor in the heightened pain reported by patients with irritable bowel syndrome and fibromyalgia. Twelve healthy subjects were recruited for this study. Simultaneous trains of electrical pulses (delivered to either the rectum or lower abdomen) and auditory tones lasting 6 s were delivered to the subjects during a whole-brain functional scan acquisition. Subjects were instructed to attend to the auditory tones (distracter task) or electrical pulses (pain task). Pain intensity ratings were significantly lower during the distraction task compared with the pain task (P < 0.01) in both sensory modalities. The left primary somatosensory cortex increased in activity with increasing pain report, during attention to visceral pain. Bilateral anterior insula (aIns) cortex activity increased with increasing somatic pain report independent of the direction of attention. Conversely, the primary and secondary auditory cortices significantly increased in activation with decreased pain report. These results suggest that pain intensity perception during attentional modulation is reflected in the primary somatosensory cortex (visceral pain) and aIns cortex activity (somatic pain).     

Dysfunction of early-stage visual processing in schizophrenia: harmonic analysis

Schizophrenia is associated with severe neurocognitive deficits that constitute a core feature of the disorder. Deficits have been most extensively studied in relationship to higher-order processes. This study evaluated the integrity of early visual processing in order to evaluate the overall pattern of visual dysfunction in schizophrenia. Steady-state visual-evoked potentials (ssVEPs) were recorded over the occipital cortex (Oz) in patients with schizophrenia and schizoaffective disorder (N=26) and in age-matched comparison volunteers (N=22). Two stimuli were used: windmill-dartboard and partial-windmill, which are contrast-reversing ( approximately 4 Hz), radial patterns with dominant low spatial-frequency content. Each stimulus was presented for 1 min. Fourier analysis was performed on the ssVEP data to extract the relevant temporal frequency (i.e., harmonic) components. Magnitude-squared coherence (MSC) was computed to estimate the relative signal level for each frequency component. The patients showed reduced amplitude and coherence of second harmonic responses in both conditions, but intact first harmonic responses in the windmill-dartboard condition. This finding of a differential deficit may indicate a significant loss in the magnocellular pathway, which contributes to the generation of the second harmonic component under these conditions. Early sensory deficits may lead to impairments in subsequent stages of processing.     

首发精神分裂症未治时间对神经认知功能P300和P50预后的影响研究

目的DUP（duration of unmedicated psychosis）指精神疾病患者首次正式开始抗精神病治疗以前其精神病状态持续存在的时间。本研究探讨首发精神分裂症DUP对其神经认知功能的影响。方法收集从未服药首次发作精神分裂症患者70例和正常对照者54例,并对50例患者完成为期2个月随访。应用诺丁汉发病量表评估患者的DUP,应用DUP中位值将患者分为长DUP组和短DUP组。应用事件相关电位P300和感觉门控P50抑制评估神经认知功能。结果与对照者相比,分裂症患者P300波幅降低（P〈0．01）,P300潜伏期延迟（P〈0．01）,感觉门控P50抑制值异常升高（P〈0．01）。治疗前,长DUP组的P300潜伏期较短DUP组有延迟（352．1ms±36．7ms,336．0ms±29．0ms;F=4．2,P〈0．05）。治疗2个月后,仅短DUP组患者的P300波幅有明显改善（5．41xV±3．01．LV,7．31．LV±2．6uV,F=8．1,P〈0．01）。同时,两组患者的感觉门控P50抑制改善均不显著。结论DUP对首发精神分裂症患者神经认知功能预后有显著影响。如何预防长DUP的发生,值得关注。     

Abnormalities of the corpus callosum in non-psychotic high-risk offspring of schizophrenia patients

Alterations in the structure of the corpus callosum (CC) have been observed in schizophrenia. Offspring of schizophrenia parents have 10-15 times higher risk for developing schizophrenia. We examined CC volume in offspring at genetic high-risk (HR) subjects. Since the sub-regions of the CC are topographically mapped to cortical brain regions, we hypothesized that HR subjects may show a decrement in total volume and differential volume decreases in sub-regions of the CC. The offspring of schizophrenia parents (HR; n = 70; 36 males) and healthy volunteers with no family or personal history of psychotic disorders (healthy controls (HC); n = 73; 37 males) matched for age, gender and education were selected for the study. Magnetic resonance images were collected using a GE 1.5 T scanner and processed using FreeSurfer image analysis software. The CC was divided into five neuroanatomically based partitions. The volume of total CC and the five sub-regions were measured blind to clinical information. With covariation for intracranial volume, HR subjects had significantly reduced total CC, more prominently observed in the anterior splenium. An age-related increase in CC volume was found in the anterior and posterior splenium of healthy controls but not in HR subjects. The volume reduction was greater in male than female HR subjects. The volume reduction in the CC may reflect a reduction in axonal fibers crossing the hemispheres and/or myelination between the left and right temporo-parietal cortices. The absence of an age-related volume increase suggests an abnormal developmental trajectory that may underlie susceptibility to schizophrenia.     

Alterations in voluntary movement execution in Huntington's disease are related to the dominant motor system — Evidence from event-related potentials

Huntington's disease is an autosomal dominant neurogenetic disorder leading to striatal atrophy, characterized by involuntary movements. Voluntary movements also deteriorate, but the neurophysiological mechanisms are less understood. We investigated voluntary movement execution and its neural correlates by means of movement-related potentials (MRPs) in symptomatic HD (HD), presymptomatic HD (pHD) and controls.Reaction times (RTs) revealed hand differences in controls and HD, but not in pHDs. Response-locked MRPs above the contralateral primary motor area (M1) were similar across all groups. Yet, the HD-group showed, selectively for the right hand, a second contralateral (left) activation after the response, followed by similar activation over the ipsilateral (right) motor area, which is normally inhibited. Similarly parietal processes were reversed for right hand movements. In strong contrast, pHDs showed an increased inhibition of the ipsilateral hemisphere.The results suggest modulations of inhibitory processes in HD dependent on disease stage. Importantly, these modulations occur after the response and are restricted to right-hand responses, or the dominant motor system (left hemisphere). Since also cognitive processes preceding the MRPs changed, the results suggest a cognitive contribution to the emergence of voluntary movement dysfunction. The pattern in the pHD-group, namely an increased inhibition of the ipsilateral hemisphere and similar RTs between the hands suggest compensatory mechanisms in presymptomatic stages of the disease. Despite neurophysiological alterations originating in the dominant left hemisphere in HDs, they also affect the right hemisphere, probably due to a dysfunction in interhemispheric inhibition in HD.