P300 generation by novel somatosensory stimuli.

Event-related potentials (ERPs) to task-relevant target and task-irrelevant novel stimuli were recorded in a somatosensory discrimination task. Subjects pressed a button to mechanical taps of the fifth finger (targets, P = 0.12), randomly interposed in sequences of taps to the second finger (standards, P = 0.76). Two types of infrequent novel stimuli were delivered; one was a mechanical tap to the third or fourth finger (tactile novels, P = 0.06), another was an electric shock at the wrist (shock novels, P = 0.06). Correctly detected targets generated a parietal maximal P300 (P3b, latency 335 msec). Shock novels generated a central maximal P300 with a shorter peak latency (298 msec) than the P3b. Tactile novels generated a P300 with a scalp distribution comparable to the shock novels. Unlike the P3b, P300 amplitude to both the shock and tactile novel stimuli habituated by 20-30% across the first several stimulus presentations. These results indicate that, similar to the auditory and visual modality, task-irrelevant novel somatosensory stimuli generate a novelty P300 ERP. Differences in scalp distribution, latency and habituation characteristics suggest that the novelty P300 may have contributions from intracranial generators independent from target P300 sources.     

Age effects on the P300 to novel somatosensory stimuli.

Event-related brain potentials (ERPs) to somatosensory task-relevant targets and task-irrelevant novel (tactile and shock) stimuli were studied in 30 subjects between the ages of 18 and 79. Target and novel P300 latencies increased linearly with age at comparable rates. P300 amplitudes and scalp topographies also changed with age. P300 amplitudes remained constant at frontal sites and decreased at central and parietal sites for both target and novel stimuli with increasing age. The current results extend the age-related novel P300 changes reported in the auditory and visual modalities to the somatosensory system. The age-related amplitude reduction at posterior scalp sites supports independent contributions of frontal and posterior association cortex to P300 generation.     

Effects of temporal-parietal lesions on the somatosensory P3 to lower limb stimulation.

Temporal-parietal junction lesions reduce the auditory and upper limb somatosensory P3 event-related potential (ERP) to target and novel stimuli. The current study examined the somatosensory P3 to target and novel stimuli delivered to the sole of the foot in patients with unilateral temporal-parietal lesions (n = 6). Age-matched controls (n = 10) generated a parietal maximal target P3 and a frontal-central maximal novelty P3 ERP to foot stimulation. Unilateral temporal-parietal lesions abolished target and novelty P3 responses over all scalp sites for stimuli delivered contralateral to the lesion. The P3 was also reduced to ipsilateral stimuli at electrodes over the lesioned hemisphere with partial P3 preservation observed at electrode sites over the non-lesioned hemisphere. These results parallel the findings for upper limb stimulation and support the critical role of temporal-parietal cortex in P3 generation.     

Impaired novelty detection and frontal lobe dysfunction in Parkinson's disease

Recent evidence suggests that the frontal lobe plays an important role in an orienting response to novel events, and that frontal lobe dysfunction is linked to attentional and cognitive deficits in Parkinson's disease (PD). We tested the hypothesis that the neural network involved in novelty detection may be impaired in PD patients by studying event-related brain potentials to target and novel stimuli and their correlation to performance in neuropsychological tests in non-demented PD patients. The PD patients showed prolonged P3 latency to novel stimuli compared with age-matched controls, whereas their P3 latency to target stimuli was not different from that in controls. The PD patients also manifested amplitude reduction and less habituation of the P3 to novel stimuli over frontal scalp sites compared with controls. The prolonged latency and frontal reduction of novelty P3 correlated with a poor performance in the Wisconsin Card Sorting Test. These results suggest that the orienting response of PD patients to novel events is impaired and that recording novelty P3 might provide a neurophysiological and quantitative measure of attentional and cognitive deficits linked to the frontal lobe in non-demented PD patients.     

Age-related changes in the electrophysiological response to visual stimulus novelty: A topographical approach

The relationship of task relevance and stimulus probability to P300 morphology, latency and distribution was assessed. Eight year olds and adults completed visual oddball tasks of recognition memory with frequent non-target (60%), infrequent target (20%), and infrequent novel (20%) stimuli. Stimuli consisted of 2 female faces posing neutral expressions, and 40 trial unique novel photographs depicting scenes, animals, objects or abstract patterns. Event-related potentials were recorded from 17 electrodes over frontal, central and parietal scalp, including lateral temporal sites. All stimuli elicited P300 responses at parietal electrodes, with the largest responses to the target stimuli (relevant and infrequent). The P300 responses of adults and children were morphologically dissimilar, with children showing broader peaks and latency shifts across electrodes. In addition, the eight year olds displayed a frontal negativity to novel stimuli which was absent in the responses of adult participants. Results suggest that different anatomical or functional circuitry may be involved in the processing of novelty for adults as compared to eight year olds.     

The influence of age and individual differences in executive function on stimulus processing in the oddball task

Studies examining the effects of aging in the oddball task have consistently revealed an age-related change in the topography of the P3 component. Specifically, in younger adults the amplitude of this component is greatest over the parietal region of the scalp while in older adults the P3 is more evenly distributed over the parietal and frontal regions of the scalp. In the current study, Partial Least Squares (PLS) analysis was used to examine the effects of age on the full time course and topography of the event-related brain potentials (ERPs) elicited during the oddball task; and to consider the influence of individual differences in executive function on age-related differences in the oddball task. Aging and individual differences appeared to have relatively little effect on the P3b that distinguished oddball stimulus from standards. The age-related “anterior shift” in the P3 appeared to result from the stronger expression of the novelty P3 in older adults relative to younger adults, as this effect was seen for both oddball and novel stimuli relative to standard stimuli. Additionally, the effect of age interacted with variation in executive function, with the novelty P3 being elicited for novel and oddball stimuli in the low executive older adults and only for novel stimuli in the high executive older adults. These findings lead to the suggestion that the age-related anterior shift in the P3 may result from the failure of older adults with lower executive functions to habituate to the oddball stimulus.     

P3a from a passive visual stimulus task

OBJECTIVE: Visual event-related brain potentials (ERPs) were elicited using a 3-stimulus oddball paradigm to assess the P3a with passive stimulus processing. METHODS: Young adults (n=12) were presented with a series of visual stimuli consisting of a solid circle standard stimulus (P=0.76) that was difficult to discriminate from a larger target circle (P=0.12), with a large square distractor stimulus (P=0.12) presented randomly in the series. Subjects were instructed in the passive condition to simply look at the stimuli and in the active condition to press a mouse key only to the target stimulus. ERPs were recorded from 15 scalp electrodes, with the amplitude and latency of the P300 from the distractor and target stimuli assessed. RESULTS: The P3a from the distractor stimulus was similar in amplitude, scalp topography, and peak latency across the passive and active task conditions. The P3b from the target stimulus demonstrated much smaller amplitude, highly altered scalp topography, and longer latency for the passive compared to active task conditions. CONCLUSIONS: The P3a can be obtained with visual stimuli in the 3-stimulus paradigm under passive viewing conditions. Theoretical implications and clinical applications are discussed.     

Pathophysiology underlying diminished attention to novel events in patients with early AD

BACKGROUND: Patients with mild to moderate AD often are apathetic and fail to attend to novel aspects of their environment. OBJECTIVE: To investigate the mechanisms underlying these changes by studying the novelty P3 response that measures shifts of attention toward novel events. METHODS: While event-related potentials were recorded, mildly impaired AD patients and matched normal controls (NC) viewed line drawings that included a repetitive background stimulus, an infrequent target stimulus, and infrequent novel stimuli. Subjects controlled how long they viewed each stimulus by pressing a button. This served as a measure of their allocation of attention. They also responded to targets by depressing a foot pedal. Patients did not differ from NC in age, education, estimated IQ, or mood but were judged by informants to be more apathetic. RESULTS: P3 amplitude to novel stimuli was significantly smaller for AD patients than NC. However, P3 amplitude to target stimuli did not differ between groups. For NC, P3 response to novel stimuli was much larger than to background stimuli. In contrast, for patients with AD, there was no difference in P3 response to novel vs background stimuli. Although NC spent more time looking at novel than background stimuli, patients with AD distributed their viewing time evenly. Remarkably, for patients with AD, the amplitude of the novelty P3 response powerfully predicted how long they would spend looking at novel stimuli (R2 = 0.52) and inversely correlated with apathy severity. CONCLUSIONS: The decreased attention to novel events exhibited by patients with AD cannot be explained by a nonspecific reduction in their attentional abilities. The novelty P3 response is markedly diminished in mild AD, at a time when the target P3 response is preserved. The disruption of the novelty P3 response predicts diminished attention to novel stimuli and is associated with the apathy exhibited by patients with AD.     

The cortical generators of P3a and P3b: a LORETA study

The P3 is probably the most well known component of the brain event-related potentials (ERPs). Using a three-tone oddball paradigm two different components can be identified: the P3b elicited by rare target stimuli and the P3a elicited by the presentation of rare non-target stimuli. Although the two components may partially overlap in time and space, they have a different scalp topography suggesting different neural generators. The present study is aimed at defining the scalp topography of the two P3 components by means of reference-independent methods and identifying their electrical cortical generators by using the low-resolution electromagnetic tomography (LORETA). ERPs were recorded during a three-tone oddball task in 32 healthy, right-handed university students. The scalp topography of the P3 components was assessed by means of the brain electrical microstates technique and their cortical sources were evaluated by LORETA. P3a and P3b showed different scalp topography and cortical sources. The P3a electrical field had a more anterior distribution as compared to the P3b and its generators were localized in cingulate, frontal and right parietal areas. P3b sources included bilateral frontal, parietal, limbic, cingulate and temporo-occipital regions. Differences in scalp topography and cortical sources suggest that the two components reflect different neural processes. Our findings on cortical generators are in line with the hypothesis that P3a reflects the automatic allocation of attention, while P3b is related to the effortful processing of task-relevant events.     

P3a and P3b from typical auditory and visual stimuli.

OBJECTIVE: Target/standard discrimination difficulty was manipulated systematically to assess how this variable affects target and nontarget P300 scalp distributions for both auditory and visual stimuli. DESIGN AND METHODS: A 3-stimulus paradigm (target, standard, nontarget) was employed in which subjects (n = 16) responded only to an infrequently occurring target stimulus. The perceptual discrimination difficulty between the target and more frequently occurring standard stimuli was varied as Easy or Difficult in different conditions, while holding the nontarget stimulus properties constant. RESULTS: When target/standard discrimination was Easy, P300 amplitude was larger for the target than the nontarget across all electrode sites, and both demonstrated parietal maximums. In contrast, when target/standard discrimination was Difficult, target amplitude (P3b) was larger parietally and occurred later than nontarget components, whereas nontarget amplitude (P3a) was larger and earlier than the target P300 over the frontal electrode sites. Similar outcomes across task conditions were obtained for both auditory and visual stimuli. CONCLUSIONS: The findings suggest that target/standard discrimination difficulty, rather than stimulus novelty, determines P3a generation for both auditory and visual stimulus modalities.     

阿尔茨海默病和血管性痴呆听觉事件相关电位P300比较研究

目的 探讨阿尔茨海默病（AD）和血管性痴呆（VD）在听觉事件相关电位P300检测中的不同特点。方法 收集符合ICD-10诊断标准的30例AD和36例VD患者,并以35例健康老人作对照组（NC）。使用丹麦仪器以及“听觉靶-非靶刺激序列”为诱发事件,完成P300检测。结果 （1）3组在靶潜伏期Cz脑区N2以及在靶波幅Cz脑区P2、P3和非靶波幅Cz脑区P2上均有显著差异（P〈0．01）。（2）AD主成分N2表现为延迟,与NC组和VD组有极显著性差异（P〈0．01）。（3）AD组和VD组靶波幅P3和非靶波幅P2均见降低,与NC组比较也有显著性差异（P〈0．05-〈0．01）。结论 提示作为反映AD和VD认知功能障碍的客观生理指标,P300有可能作为AD和VD辅助诊断的一个脑电生理学标志。P300检查可作为老年神经精神科的必查项目。     

Alzheimer病与血管性痴呆患者认知功能对照研究

目的探讨Alzheimer病与血管性痴呆患者认知功能状况及其之间差异。方法对36例临床诊断的Alzheimer病、35例血管性痴呆患者及35例健康人进行了事件相关电位(ERP)和简易智力状态检查(MMSE)测试。结果Alzheimer病组、血管性痴呆组ERP测定的异常率为94.4%(34/36)和85.7%(30/35),两组ERP中N2、P3波潜伏期较正常对照组延长,P3波幅降低,其差异具有统计学意义(P<0.01);而Alzheimer病组ERP测定N2、P3波潜伏期较血管性痴呆组延长,P3波幅降低,其差异具有统计学意义(P<0.05)。Alzheimer病组、血管性痴呆组MMSE量表总分值与分量表得分值较正常组降低,差异具有统计学意义(P<0.01,P<0.05);Alzheimer病组与血管性痴呆组比较,在MMSE量表总分、时间定向及物体命名等分值明显降低,差异具有统计学意义(P<0.05)。结论Alzheimer病与血管性痴呆患者均存在明显的认知功能减退,且Alzheimer病认知损害更为明显。     

Frontal and parietal components of a cerebral network mediating voluntary attention to novel events

Despite the important role that attending to novel events plays in human behavior, there is limited information about the neuroanatomical underpinnings of this vital activity. This study investigated the relative contributions of the frontal and posterior parietal lobes to the differential processing of novel and target stimuli under an experimental condition in which subjects actively directed attention to novel events. Event-related potentials were recorded from well-matched frontal patients, parietal patients, and non-brain-injured subjects who controlled their viewing duration (by button press) of line drawings that included a frequent, repetitive background stimulus, an infrequent target stimulus, and infrequent, novel visual stimuli. Subjects also responded to target stimuli by pressing a foot pedal. Damage to the frontal cortex resulted in a much greater disruption of response to novel stimuli than to designated targets. Frontal patients exhibited a widely distributed, profound reduction of the novelty P3 response and a marked diminution of the viewing duration of novel events. In contrast, damage to posterior parietal lobes was associated with a substantial reduction of both target P3 and novelty P3 amplitude; however, there was less disruption of the processing of novel than of target stimuli. We conclude that two nodes of the neuroanatomical network for responding to and processing novelty are the prefrontal and posterior parietal regions, which participate in the voluntary allocation of attention to novel events. Injury to this network is indexed by reduced novelty P3 amplitude, which is tightly associated with diminished attention to novel stimuli. The prefrontal cortex may serve as the central node in determining the allocation of attentional resources to novel events, whereas the posterior parietal lobe may provide the neural substrate for the dynamic process of updating one's internal model of the environment to take into account a novel event.     

Clinical application of the P3 component of event-related potentials. I. Normal aging

Normal adult volunteer subjects ranging in age from 18 to 90 years participated in a study in which analogous auditory and visual paradigms, with infrequently occurring target and non-target events, were used to elicit event-related potentials (ERPs) with a prominent P3 component. Of the 135 subjects participating, 66 completed both auditory and visual paradigms. The amplitude and latency of P3 were analyzed using average ERPs, single trials (adaptive filter) and principal components analysis (PCA). Age regressions were calculated using measures derived from average ERPs and single trials. Single trial measures were better than average ERP measures in demonstrating age-related changes in P3 latency. There was a significant increase in P3 latency with age of 1-1.5 msec/year. The range of normal P3 latency for a given age (1 S.E. of the regression = 40 msec for the visual target stimuli) was much larger than obtained by other investigators. The visual paradigm produced higher P3 latency/age correlations than the auditory paradigm (visual target r = 0.52, non-target r = 0.42; auditory target r = 0.32, non-target r = 0.33). Within individuals, the amplitude and latency of P3 generated by auditory and visual stimuli were highly correlated, though the visual paradigm produced larger and later P3s than the auditory paradigm. There is an apparent change in the scalp topography of P3 with age. In young adults, P3s to target stimuli have a markedly parietal distribution. The distribution of P3 becomes more uniformly distributed from Pz to Fz with age. This may be due to changes in overlapping components such as the slow wave (SW) rather than to changes in the amplitude of P3 per se.     

Anterior and posterior association cortex contributions to the somatosensory P300

A P300 (P3)-evoked response is generated in a variety of mammalian species upon detection of significant environmental events. The P3 component has been proposed to index a neural system involved in attention and memory capacity. We investigated the contribution of anterior and posterior association cortex to somatosensory P3 generation. Somatosensory event-related potentials (ERPs) were recorded in controls (n = 10) and patients with unilateral lesions in temporal-parietal junction (n = 8), lateral parietal cortex (n = 8), or dorsolateral frontal cortex (n = 10). Subjects pressed a button to mechanical taps of the fifth finger (targets; p = 0.12), randomly interposed in sequences of taps to the second (standards; p = 0.76) and the third or fourth finger (tactile novels; p = 0.06). Occasional shock stimuli were delivered to the wrist (shock novels; p = 0.06). The scalp-recorded P3 was differentially affected by anterior and posterior association cortex lesions. Subjects with temporal-parietal lesions showed markedly reduced P3s to all types of stimuli at all scalp locations. The reductions were largest at the parietal electrode site over the lesioned hemisphere. Parietal patients had normal P3s for all stimulus types except for contralateral shock novels, which generated reduced P3s. Frontal lesions had reductions of the novelty P3 over frontal sites with minimal changes in the target P3. The data support the existence of multiple intracranial P3 sources. The data further indicate that association cortex in the temporal-parietal junction is critical for generating the scalp-recorded target and novelty P3s, whereas dorsolateral frontal cortex contributes preferentially to novelty P3 generation. The N2 component was reduced by parietal and frontal lesions in patients who had intact target P3s, suggesting that different neural systems underlie N2 and P3 generation.     

Predictive value of novel stimuli modifies visual event-related potentials and behavior.

OBJECTIVE: We examined how behavioral context influences novelty processing by varying the degree that a novel event predicted the occurrence of a subsequent target stimulus. METHODS: Visual event-related potentials (ERPs) and reaction times (RTs) were recorded in 3 detection experiments (23 subjects). The predictive value of a novel stimulus on the occurrence of a subsequent target was varied as was novel-target pairing intervals (200-900 ms). In Experiment 1, novel stimuli always preceded a target, in Experiment 2, 40% of novel stimuli were followed by a target, and in Experiment 3, novel stimuli occurred randomly. RESULTS: In Experiment 1, RTs following 100% predictive novels were shortened for targets at all spatial locations and novel-target pairing intervals. Novel stimuli predicting a target generated a central negativity peaking at 300 ms and reduced P3a and P3b ERPs. In Experiments 2 and 3, target RTs were prolonged only when novel and target stimuli were presented in the same spatial location at short ISIs (200 ms). The central novel N2 was smaller in amplitude in comparison to Experiment 1, and novelty P3a and target extrastriate N2 and posterior scalp P3b ERPs were enhanced. CONCLUSIONS: The enhanced N2 for 100% predictive novel stimuli appears to index an alerting system facilitating behavioral detection. The same novel stimuli with no predictive value distract attention and generate a different ERP pattern characterized by increased novelty P3a and target P3b responses. The results indicate that behavioral context determines how novel stimuli are processed and influence behavior.     

Reproducibility of the hemodynamic response to auditory oddball stimuli: a six-week test-retest study

Determining the reliability and reproducibility of the hemodynamic response is important for the interpretation and understanding of the results of functional magnetic resonance imaging (fMRI) experiments. We describe a whole brain fMRI study designed to examine the reproducibility of the event-related hemodynamic response elicited by low-probability task-relevant target stimuli and low-probability task-irrelevant novel stimuli assessed 6 weeks apart. Reliable activation was observed during test and retest for processing of target stimuli in multiple frontal, temporal, parietal, cerebellar, and subcortical sites. Novel stimuli elicited reliable activation during test and retest in lateral frontal cortex, inferior parietal lobule, and lateral temporal cortex, though there was evidence of habituation at some cortical sites. The patterns of activation associated with target detection and novelty processing are consistent with the intracranial distribution of the neural sources generated during similar tasks and replicate the results of previous event-related fMRI studies. The observed pattern of results supports the hypothesis that the hemodynamic response to target and novel stimuli is highly reproducible over the 6-week test-retest period.     

Auditory and visual P300 topography from a 3 stimulus paradigm.

OBJECTIVE: The P300 event-related brain potential (ERP) was elicited with auditory and visual stimuli in a separate session of a 3 stimulus oddball paradigm, and the scalp topography was assessed with 15 electrode locations. METHODS: Target (0.10), standard (0.80), and infrequent non-target (0.10) stimuli in the auditory task were 2000, 1000 and 500 Hz tone, and in the visual task, 'X', 'O', and 'H', respectively. The stimuli were presented in a random series, once every 2 s, and participants responded only to the target (N = 12). RESULTS: Target stimuli elicited larger P300 components than non-target did in both stimulus modalities. For both target and non-target stimuli, P300 amplitude was larger and latency longer for the visual compared with the auditory stimulus. Analysis of normalized P300 amplitude data indicated that the target and non-target P300s from both modalities had identical topography. CONCLUSION: The findings suggest that both target and non-target stimuli in 3 stimulus oddball paradigm elicited the same type of P300 (P3b) for both stimulus modalities.     

What is novel in the novelty oddball paradigm? Functional significance of the novelty P3 event-related potential as revealed by independent component analysis

To better understand whether voluntary attention affects how the brain processes novel events, variants of the auditory novelty oddball paradigm were presented to two different groups of human volunteers. One group of subjects (n=16) silently counted rarely presented 'infrequent' tones (p=0.10), interspersed with 'novel' task-irrelevant unique environmental sounds (p=0.10) and frequently presented 'standard' tones (p=0.80). A second group of subjects (n=17) silently counted the 'novel' environmental sounds, the 'infrequent' tones now serving as the task-irrelevant deviant events. Analysis of event-related potentials (ERPs) recorded from 63 scalp channels suggested a spatiotemporal overlap of fronto-central novelty P3 and centro-parietal P3 (P3b) ERP features in both groups. Application of independent component analysis (ICA) to concatenated single trials revealed two independent component clusters that accounted for portions of the novelty P3 and P3b response features, respectively. The P3b-related ICA cluster contributed to the novelty P3 amplitude response to novel environmental sounds. In contrast to the scalp ERPs, the amplitude of the novelty P3 related cluster was not affected by voluntary attention, that is, by the target/nontarget distinction. This result demonstrates the usefulness of ICA for disentangling spatiotemporally overlapping ERP processes and provides evidence that task irrelevance is not a necessary feature of novelty processing.     

Luminance and spatial attention effects on early visual processing

Event-related potentials (ERPs) were recorded from healthy subjects in response to unilaterally flashed high and low luminance bar stimuli presented randomly to left and right field locations. Their task was to covertly and selectively attend to either the left or right stimulus locations (separate blocks) in order to detect infrequent shorter target bars of either luminance. Independent of attention, higher stimulus luminance resulted in higher ERP amplitudes for the posterior N95 (80–110 ms), occipital P1 (110–140 ms), and parietal N1 (130–180 ms). Brighter stimuli also resulted in shorter peak latency for the occipital N1 component (135–220 ms); this effect was not observed for the N1 components over parietal, central or frontal regions. Significant attention-related amplitude modulations were obtained for the occipital P1, occipital, parietal and central N1, the occipital and parietal P2, and the parietal N2 components; these components were larger to stimuli at the attended location. In contrast to the relatively short latencies of both spatial attention and luminance effects, the first interaction between luminance and spatial attention effects was observed for the P3 component to the target stimuli (350–750 ms). This suggests that interactions of spatial attention and stimulus luminance previously reported for reaction time measures may not reflect the earliest stages of sensory/perceptual processing. Differences in the way in which luminance and attention affected the occipital P1, occipital N1 and parietal N1 components suggest dissociations among these ERPs in the mechanisms of visual and attentional processing they reflect. Nonetheless, scalp current density mappings of the attention effects throughout the latency ranges of the P1 and N1 components show the most prominent attention-related activity to be in lateral occipital scalp areas. Such a pattern is consistent with the spatially selective filtering of information into the ventral stream of visual processing which is reponsible for complex feature analysis and object identification.