P300 decrements in teenagers with conduct problems: implications for substance abuse risk and brain development.

BACKGROUND: The purpose of this study was to evaluate the effects of conduct disorder problems, family history, gender, and age on P300 electroencephalographic potentials in teenagers. METHODS: The 257 subjects, aged 15 to 20 years, were assigned to one of twelve groups defined by the crossing of three between-subjects factors: 1) gender; 2) ranking below vs above the median number of conduct disorder problems for their gender; and 3) no family history of alcohol or drug dependence vs familial alcohol dependence vs familial heroin or cocaine dependence. RESULTS: P300 amplitude was smaller among subjects reporting a greater number of conduct problems prior to age 15 vs those reporting fewer problems of this type. No family history effects were detected. Another set of analyses examined the effects of age on conduct problem-related decrements in P300. Smaller P300 amplitudes within the posterior scalp region were associated with a greater number of conduct problems among subjects younger than 16.5 years. Among subjects greater than this median age, the effects of these behaviors were only apparent over the frontal scalp. CONCLUSIONS: It is concluded that P300 decrements previously attributed to familial alcohol/substance dependence might be the result of a coincident increase in the prevalence of conduct disorder problems. The analysis of age interactions suggests that P300 amplitude decrements observed at posterior scalp sites among subjects with more conduct problems disappear at approximately 16 to 17 years of age. After that age, decrements in frontal brain function may begin to emerge in the subset of conduct problem subjects who are at risk for developing adult antisocial personality disorder.     

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.     

Event-related brain potentials in response to novel sounds in dementia.

OBJECTIVE: Non-target, deviant stimuli generate an earlier latency, front-central novelty P3, whereas correctly detected task-relevant stimuli generate a parietal maximal target P3. We examined whether the P3 component to novel stimuli is affected by dementing processes, and is therefore useful for distinguishing Alzheimer's type dementia (AD) from vascular dementia (VD). METHODS: We recorded ERPs to task-relevant stimuli (target P3) and novel task-irrelevant stimuli (novelty P3) in an auditory oddball task in AD (n = 16), VD (n = 16), and age-matched controls (n = 18). The amplitude, latency, and scalp topography of target and novelty P3 were compared among 3 groups using ANOVA. The relationship between P3 measures and intelligence scores were evaluated by correlation analysis. RESULTS: The amplitude, latency and scalp topography of the target P3 were comparably affected by both AD and VD. However, the amplitude of the novelty P3 was markedly reduced in VD, but not in AD, and the scalp topographics were different in the 3 groups. The amplitude was maximal at frontal sites in controls, at central sites in AD, and at parietal sites in VD. The target P3 latency was prolonged in both AD and VD, whereas the novelty P3 latency was only prolonged in VD. AD was discriminated satisfactorily from VD by using the novelty amplitude at Cz and the ratio of the amplitudes at Fz and Pz as independent variables. CONCLUSIONS: These results suggest that the response to novel stimuli is differentially affected by dementia with degenerative and vascular etiology.     

The effects of aging on the P3 component of the visual event-related potential

Visual stimuli were used to elicit ERPs in 108 normal subjects ranging in age from 8 to 90 years. Age-related differences were found for both P3 latency and amplitude. Children and elderly adults were found to have the latest P3s. The earliest P3s were found in subjects in their twenties. A curvilinear function best described the P3 latency/age relationship. Also, small but significant differences were observed between males and females in P3 latency. The relationship between P3 amplitude and age was strongly influenced by scalp location. P3 was largest at posterior electrode sites, but was not visible at frontal sites in young children. With increasing age P3 decreased in amplitude at the posterior sites and increased in amplitude at more frontal locations.     

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.     

Differential auditory processing continues during sleep.

Auditory evoked potentials (AEPs) were used to examine selective stimulus processing in sleep. In waking, repetitive stimuli generate exogenous P1, N1 and P2 components of the auditory evoked potential (AEP). Deviant stimuli generate endogenous cognitive components including the mismatch negativity (MMN), N2 and P3 components. We examined long-latency auditory evoked potentials elicited by repetitive and deviant stimuli during waking and stage II-IV sleep to assess whether stimulus deviance is detected during sleep. The waking P1, N1b and P2 had maximal amplitudes at fronto-central scalp sites, with additional peaks (N1a, N1c) at temporal sites. Deviant tones generated a frontal maximal MMN, and complex novel tones generated an additional P3 component maximal at centro-parietal sites. During stages II-IV sleep N1a, b, c amplitudes were reduced. During stage II sleep all stimuli generated increased P2 amplitudes and a late negative component (N340). Deviant stimuli generated greater P2 and N340 amplitudes than frequent stimuli in stage II sleep, as well as an additional P420 component. In stage III-IV sleep the P420 was absent and the AEP was dominated by a negativity of long duration whose amplitude increased in response to deviant stimuli. These data indicate that auditory evoked activity changes from wakefulness to sleep. The differential response to deviant sounds observed during waking and all sleep stages supports the theory that selective processing of auditory stimuli persists during sleep.     

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.     

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.     

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.     

A subcortical correlate of P300 in man

Event-related potentials in visual and auditory target detection tasks were recorded simultaneously from the scalp, somatosensory thalamus and periaqueductal gray in a chronic pain patient with electrodes implanted subcortically for therapeutic purposes. Short latency tactile responses confirmed the location of the thalamic electrodes. Rare auditory stimuli which were detected by the subject were accompanied by a prominent P300 component at the scalp, and by negative activity at the subcortical sites with the same latency as the scalp positivity. This activity was not seen in responses to frequent non-target stimuli and was not dependent on an overt motor response. Similarly, rare visual stimuli generated a scalp P300 and negative activity subcortically; both scalp and subcortical waves had a longer latency than in the auditory experiment. The reaction time was similarly longer to visual targets. These data are inconsistent with a hippocampal generator for P300, but are consistent with a generator in the thalamus or more dorsally located structures.     

Somatosensory disinhibition and frontal alien hand signs following medial frontal damage.

We report augmentation of somatosensory evoked potentials (SEP) in a patient with frontal alien hand signs after left medial frontal lobe damage. The SEP components occurring later than 30 msec post stimuli were enhanced over the parietal and frontal scalp sites of the lesioned hemisphere. This finding suggests that deficits in inhibitory control of somatosensory processing in parietal and frontal lobes contributes in some way to frontal alien hand signs.     

Dipolar source modeling of the P300 event-related potential after somatosensory stimulation.

The cerebral generators of the P300 potential evoked by somatosensory stimuli were investigated. Event-related potentials elicited by an oddball paradigm were recorded in 15 healthy subjects by 19 scalp electrodes. Nontarget and target electric stimuli were delivered on the anterior surface of the left elbow and of the wrist, respectively. Target traces showed an N140 potential followed by a widely distributed P300 response. Dipolar source modeling of target traces resulted in a six-dipole model. In the earlier latency range (up to 200 ms), one dipole in the contralateral perirolandic region and two dipoles in the parasylvian cortex of both hemispheres were activated. Two dipolar sources located bilaterally in the medial temporal region (MTR) showed their maximal activity at the P300 latency. Finally, a dipole in the contralateral frontal lobe was activated both at the latency of the N140 response and after 200 ms. It was found that two symmetrical MTR sources and a frontal dipole contributed to P300 generation.     

ERP amplitude and scalp distribution to target and novel events: effects of temporal order in young,middle-aged and older adults

Event-related brain potentials (ERPs) were recorded from young (mean age = 24.1), middle-aged (48.7) and older (69.7) adults during a version of the oddball paradigm, in which 48 unique, unexpected novel stimuli were interspersed with equally rare instructed targets. As older relative to younger adults are thought to differ in their ability to inhibit the processing of task irrelevant information, we expected, based on previous work, that novel stimuli would retain their ‘novelty’ longer in older than in younger adults. To assess this, P3 amplitude and scalp topography elicited by novels and targets were analyzed as a function of stimulus number (n = 6) within the block and as a function of block number (n = 4). The results were in line with prediction: While the younger adults' P3 scalp distribution shifted from a relatively more frontal to a relatively more posterior focus as a function of novel number within the block, this was not evident in the scalp topographies of the older adults. Coupled with the older adults' elevated false alarm rates to novel stimuli, the data are consistent with a change in frontal lobe function with increases in age.     

Auditory event-related responses in children with semi-lobar holoprosencephaly

The purpose of this study was to evaluate auditory sensory and discrimination responses in children with semi-lobar holoprosencephaly (HPE). Event-related potential (ERP) signals were recorded to tone pair stimuli at 62 electrode sites from the scalp using an oddball paradigm (a two-block design, inter-stimulus interval=70 or 300 ms; frequency of tone pair=100 vs. 100 Hz for the frequent and 100 vs. 300 Hz for the infrequent). Latencies and amplitudes of P150, N250, and mismatch negativity (MMN)-like components were compared between children with HPE and controls. Our results revealed less organized ERP waveforms to both stimuli in children with HPE, with diminished P150 and N250 components across brain area. Robust and delayed MMN-like responses were elicited from the children with HPE, with decreased MMN amplitudes in the central, parietal, occipital, and posterior temporal areas. Our results suggest that while brain sensory responses to auditory tones may be impaired in children with semi-lobar HPE, subcomponents of auditory discrimination processes remain functional.     

Transient global ischemia specifically modulates visual P300 scalp distribution.

OBJECTIVE: Latency, amplitude, and scalp topography of the visual P300 component was examined in patients who had suffered from transient global ischemia (TGI) due to cardiac arrest and in age matched clinical and healthy controls in order to investigate the diagnostic value of this component. METHOD: Event-related potentials (ERPs) were recorded from 19 scalp electrodes in a visual oddball paradigm. RESULTS: Mean latency of the P300 component was prolonged in both patient groups. Changes in scalp distribution of the P300, however, appear to be specific to anoxic-ischemic encephalopathy. In particular, a selective reduction of the P300 amplitudes at posterior recording sites was observed in TGI patients. Moreover, examination of the auditory P300 in TGI patients revealed that this selective change seems to be restricted to the visual modality. CONCLUSION: The results are discussed with respect to selective vulnerability of brain tissue to hypoxic-ischemic injury. After TGI a modality-specific subset of P300 generators, probably located in the transitional parieto-occipital and extrastriate occipital cortex, appears to be affected. It is also noted, that the visual P300 component could serve as an additional marker of TGI especially in patients who do not show neuropathological changes in structural brain images.     

Brain responses to tonal changes in the first two years of life

Maturation of auditory perceptual and discrimination process within the first two years of life is investigated in healthy infants by examining event-related potentials (ERPs). High-density EEG signals were recorded from the scalp monthly between 3 and 24 months of age. Two types of stimuli (100 vs. 100 Hz for standard stimuli; 100 vs. 300 Hz for deviant stimuli; occurrence rate: 85:15%) were presented using an oddball paradigm. Latencies and amplitudes were compared across development. The results showed that latencies of P150, N250, P350, and N450 components gradually decreased with increasing age. Amplitudes of the N250 and P350 components gradually increased and reached the maximum at 9 months, and then gradually decreased with the increase of age. Mismatch negativity was not obvious at 3 months of age, but was seen at 4-5 months and became robust after 6 months. Robust late positivity was recorded at all ages. These mismatch responses were noticeable in the frontal, central, and parietal areas, and the maximal MMN amplitude distribution gradually moved from the parietal area to the frontal area across the age range. Two important periods--one around 6 months and the other around 9 months are suggested in the maturation of auditory central system. Dynamical changes in the underlying source strengths and orientations may be principal contributors to ERP morphological changes in infants within the first 24 months.     

Auditory selective attention in middle-aged and elderly subjects: an event-related brain potential study.

Reaction times (RTs) and event-related brain potentials (ERPs) were recorded in middle-aged (MA) and elderly (ELD) subjects performing an auditory selective attention task. Subjects attended to tone bursts of a specified pitch and ear of delivery and responded to occasional longer duration target tones (75 vs. 25 msec). Infrequent novel stimuli (computer synthesized sounds and digitized environmental noises) were also included in the stimulus sequence. No significant age-related differences were found in the speed or accuracy of target detection. However, in both groups, RTs were delayed (by more than 300 msec) to targets that followed novel sounds. The prolongation was greater following novel sounds in the attended ear, particularly in the ELD group. The effects of selective attention on ERPs to standard tones were isolated as negative difference waves (Nds) by substracting ERPs to non-attended stimuli from ERPs to the same signals when attended. Nds had similar amplitudes, latencies of onset (60 msec), and distributions in ELD and MA groups. In both groups, Nd waves were more prominent following right ear stimulation, reflecting possible hemispheric asymmetries of generators in posterior temporal regions. The mismatch negativity (MMN) was isolated by subtracting ERPs to standard tones from ERPs to deviant stimuli. MMN amplitudes were reduced in the ELD group. There was also a significant change in MMN distribution with age: the MMN was larger over the right hemisphere for MA subjects but larger over the left for ELD subjects. Elderly subjects showed a trend toward smaller P3 amplitudes and delayed P3 latencies, but group differences did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stimulus novelty differentially affects attentional allocation in PTSD.

BACKGROUND: This study investigated attentional allocation in 39 Vietnam combat veterans, 25 with and 14 without posttraumatic stress disorder, assessing P300 amplitudes and latencies during both three-tone and novelty "oddball" tasks. METHODS: The three-tone oddball task consisted of three stimuli: frequent tones (85%), rare target tones (7.5%), and rare distractor tones (7.5%). The novelty oddball task was identical to the three-tone task except that the rare distractor tones were replaced with nonrepeating novel sounds (7.5%). RESULTS: Combat veterans with posttraumatic stress disorder showed significant P300 amplitude enhancements at frontal sites in response to distracting stimuli during the novelty but not during the three-tone oddball tasks. There were no amplitude differences in target tones during either task. CONCLUSIONS: The data suggest that combat veterans with posttraumatic stress disorder demonstrate P300 responses consistent with a heightened orientation response to novel, distracting stimuli. This finding is consistent both with the clinical presentation of the disorder and with theoretical notions that individuals with posttraumatic stress disorder demonstrate information-processing biases towards vague or potentially threatening stimuli.     

Total sleep deprivation and novelty processing: implications for frontal lobe functioning.

OBJECTIVE: Mounting evidence suggests that the frontal lobes are particularly vulnerable to total sleep deprivation (TSD). Detection of novelty involves the frontal lobes. The presentation of rare, novel stimuli elicits an event-related potential (novel P3), which maximizes over anterior regions of the scalp. We hypothesized that TSD would impair novelty detection, resulting in a smaller novel P3 over the frontal region, with a topographic shift toward posterior areas. METHODS: An auditory novelty oddball task was administered to a TSD group after 36 h of waking and again following recovery sleep, and to a control group after 12 h of waking. EEG was recorded from Fz, Cz and Pz. RESULTS: A large anterior P3 was elicited in the control group. In the TSD group, this novel P3 was smaller at Fz. A later novel positivity appeared in parietal areas. The novel P3 returned to baseline levels and the late novel P3 was difficult to observe following recovery sleep. CONCLUSIONS: TSD appears to compromise the usual automatic detection of novelty probably due to frontal deactivation. Participants may compensate by relying on posterior brain mechanisms involving active memory comparison. The late novel P3 component may also reflect a secondary effortful attempt to encode and to categorize novel stimuli. SIGNIFICANCE: This study suggests that TSD may compromise cognitive functioning in different regions of the brain. The detection of novelty, probably mediated by the frontal lobes, is particularly at risk.     

A cortical potential imaging analysis of the P300 and novelty P3 components

The P300 and Novelty P3 are positive components of the event related brain potential (ERP) with a latency of at least 300 ms, which are manifestations of brain activity evoked by deviant events. Spencer et al. [1999, 2001] demonstrated that these are two distinct components, both of which may be elicited, with different amplitudes, by both rare and novel events. However, the locations of the intracranial sources of the components remain unknown. We describe the application of cortical potential imaging (CPI) analysis to the data described by Spencer et al. [1999]. The ERPs were recorded from 15 healthy subjects presented with auditory oddball sequences. Cortical potential maps (CPMs) were reconstructed from the scalp potential maps (SPMs) corresponding to the P300 and Novelty P3 components by deblurring the smoothing effect of the head volume conductor. The reconstructed CPMs, derived from the SPMs by means of the CPI, showed localized areas of activity distributed in both the frontal and parietal lobes; the parietal region was active throughout the period of the late positivities. The reconstructed CPMs associated with novel events showed prominent activity at the frontal lobe (Novelty P3) followed by progressively pronounced parietal lobe activity (P300), and these two components can be well separated by the CPMs. These analyses show how the CPI can be used to relate the scalp electrical recordings to the underlying brain activity.