Latency variability of the components of auditory event-related potentials to infrequent stimuli in aging, Alzheimer-type dementia, and depression

Auditory event-related potentials (ERPs) were investigated in 15 demented (12 presumed Alzheimer's, 3 cerebrovascular), 8 depressed, and 15 normal older, and 12 normal young, subjects. Both latencies from conventional averages and latency variability measures from single trials were derived for the N100, P200, N200, and P300 components of the ERP recorded from Fz, Cz and Pz scalp placements in a task requiring detection of an infrequent target tone among a series of frequent non-target tones. The P300 component most consistently separated the groups. Demented subjects had longer P300 latencies and greater P300 latency variability than both control groups and the depressed group. Age differences were observed for P300 latency, but not for P300 latency variability. Amplitudes were not significantly different among the groups. Reaction times (RTs) to the targets were longest for the demented subjects and shortest for the young controls, with the depressed and normal older control groups falling in between. Correlations between RT and P300 latency from single trials did not differentiate the groups. Using regression analysis to evaluate the deviation of P300 latency and latency variability for the patients from the predicted values for normal controls, no misclassifications of depressed patients occurred, but only 27% of the demented individuals were correctly classified using P300 variability, and 13% using P300 latency. These findings indicate that ERP measures using the 'oddball' target detection paradigm were useful in describing group differences, but were not sufficiently sensitive to be used in differentiating demented persons on an individual basis for clinical diagnosis.     

N1 and P2 components of auditory event-related potentials in children with and without reading disabilities.

OBJECTIVE: The effects of within stimulus presentation rate and rise time on basic auditory processing were investigated in children with reading disabilities and typically reading children. METHODS: Children with reading disabilities (RD; N=19) and control children (N=20) were studied using event-related potentials (ERPs). Paired stimuli were used with two different within-pair-intervals (WPI; 10 and 255 ms) and two different rise times (10 and 130 ms). Each stimulus was presented with equal probability and long between-pair inter-stimulus intervals (1-5s). The study focused on N1 and P2 components. RESULTS: The P2 responses to the first tone in the pair showed differences between children with RD and control children. Also, children with RD had larger N1 response than control children to stimuli with short WPI and long rise time. CONCLUSIONS: These results provide evidence for basic auditory processing abnormalities in children with RD. This processing difference could be related to extraction of stimulus features from sounds or to attentional mechanisms. SIGNIFICANCE: Our results show support for behavioral findings that children with RD and control children process rise times differently. More than half of children with RD showed atypical auditory processing.     

Latency of the P3 event-related potential: normative aspects and within-subject variability

A growing body of research has focused on the P3 (P300) event-related potential as an electrophysiological correlate of selective attention. The present investigation examines the intrasubject test-retest reliability of the auditory evoked P3 latency measure for neurologically and audiologically normal young adults aged 22-34 years across test sessions separated by 2-4 weeks (N = 9) and across trials within one test session (N = 20). In a target-selection ('oddball') paradigm, subjects mentally counted infrequent 2 kHz tone bursts (targets) randomly interspersed within a sequence of 1 kHz tone bursts (non-targets). A strong positive correlation was demonstrated between latencies of test sessions I and II. An analysis of variance did not demonstrate statistically significant latency differences as a function of either tests or trials for the test-retest group (N = 9). Although analysis of variance demonstrated a statistically significant difference between trials within one test session for 20 subjects, the small mean latency difference between trials (4.7 msec) is interpreted as being clinically unimportant. The stability of P3 latency found in this study over a period of 2-4 weeks supports its application to the study of normal and disordered cognitive processes.     

The mismatch negativity and the P3a components of the auditory event-related potentials in autistic low-functioning subjects.

OBJECTIVE: In order to understand better the psychophysiological basis of auditory processing abnormalities in autism, we decided to study two automatic components of the auditory event-related potentials (ERPs): the mismatch negativity (MMN)--a component of the ERP which is recorded when, during repetitive auditory stimulation, rare changes are introduced--and the novelty-related P3a which is recorded as a response to unexpected novel events occurring in a sequence of repetitive stimuli. METHODS: Ten male subjects, mean age 12.3 years (SD 4.95), affected by autism and mental retardation were admitted to this study. All patients were also mentally retarded. Ten normal male subjects, mean age 12.2 years (SD 3.94), were used as controls. Auditory evoked potentials were recorded from 19 scalp electrodes (10-20 system), and stimuli were presented in sequences consisting of 2000 tones (70 dB, ISI=800 ms). Three types of stimuli were presented: (1) standard stimuli (1000 Hz tones, 80% of total stimuli), (2) deviant stimuli (1300 Hz tones, 10% of total stimuli), and (3) novel stimuli (complex and non-monotonal, 10% of total stimuli). To quantify the MMN, the evoked response to the standard tones was subtracted from the corresponding deviant stimulus response and its amplitude and latency at peak were measured over Fz, Cz and Pz; similarly, the P3a component of the ERP was obtained by subtracting the response to the standard tone from that to the novel stimuli and its amplitude and latency at peak were measured over Fz, Cz and Pz. Also, the amplitude and latency at peak for the N1 component of the auditory evoked potential obtained with the standard stimuli were measured over Fz, Cz and Pz. The correlation between age and MMN and P3a amplitude was also analyzed. RESULTS: N1 showed significantly shorter latencies in the autistic groups. MMN elicited by deviant stimuli, but not that elicited by novel stimuli, was found to be significantly larger in autistic children than in normal controls. P3a showed higher amplitude in autistic subjects than in normal controls during childhood; the opposite was observed during young adulthood. DISCUSSION: Our findings indicate that significant changes in ERPs can also be seen in non-cooperative individuals with autism and mental retardation, which might be different from the changes already reported for high-functioning autistic subjects and deserve further insight. These changes show developmental modifications that should be taken into consideration when analyzing data from autistic subjects.     

The localizing value of auditory event-related potentials (P300) in patients with medically intractable temporal lobe epilepsy

The localizing value of postictal versus interictal event-related potentials (ERPs) was studied in patients with medically intractable TLE admitted for long-term video EEG monitoring. Ten patients with partial seizures and secondary generalization underwent preictal (upon hospital admission), postictal (6 h after seizure), and interictal (7–48 h after seizure) ERP recordings of an auditory oddball paradigm. Preictal ERPs were compared to postictal and interictal recordings. Intraclass correlations, transformed into z scores, were utilized to analyze amplitude differences between electrodes placed on the hemisphere ipsilateral versus contralateral to the epileptogenic focus. The results showed that in 9 out of 10 patients the ERP amplitude was reduced in postictal compared to preictal recordings for electrodes placed ipsilateral to the epileptogenic focus (P<0.0001). However, there was no difference in amplitude between ipsilateral and contralateral electrodes in preictal and interictal recordings. These findings suggest that postictal ERPs are of localizing value in patients with TLE while interictal ERPs are not.     

P300 component of the auditory event-related potentials and dyslexia

Ten normal children (mean age = 9 years) and 12 dyslexic children (mean age = 8.1 years) were compared for latency, amplitude and topographic distribution of both parameters of P300. We found a significant increase in P300 latency in the dyslexic group. Noteworthy is the increase in amplitude in the central parietal area in the control group. These facts and their incidence are discussed in the present study.     

Reliability of the task-related component (P3b) of P3 event-related potentials

Abstract Within session and between session reliabilities of the task-related component (P3b) of the P3 measures (amplitude, area and latency) and their habituation across eight sessions separated by 7–10 days, except for an interval of 1 month between the 6th and 7th sessions, were studied based on the difference waves, which were obtained by subtracting the ignored infrequent event-related potentials (ERP) from the target ERP elicited by a standard auditory oddball paradigm with eyes-open or eyes-closed conditions in 10 normal subjects. The within session reliabilities represented as Pearson correlation coefficients ( r ) were 0.57-0.66 for the three measures except for those for the latency and amplitude under the eyes-closed condition. The between session reliabilities expressed as intraclass correlation coefficients ( R ) ranged from 0.54 to 0.60 except for that for latency under eyes-closed conditions. Long-term habituation occurred within the first six sessions for the P3b amplitude and area, and dishabituation took place in the 7th session after an interval of 1 month, whereas no such phenomenon was observed for the P3b latency. Implications of the present results are discussed in terms of the clinical application of the P3 measures.     

Delayed P3 event-related potentials (ERPs) in thalamic hemorrhage

Delayed P3 ERPs were recorded with an acoustic oddball paradigm in 5 patients affected by unilateral thalamic hemorrhage. P3 latencies in these 5 patients were above the normal mean latency of age-matched controls +2/ +3 S.D.s. The P3 delay was persistent in serial follow-ups at 6 months from stroke. Normal P3 latencies were instead recorded in 4 patients with paramedian hemorrhage not involving or only partially involving the thalamus.     

Delayed P3 event-related potentials (ERPs) in thalamic hemorrhage.

Delayed P3 ERPs were recorded with an acoustic oddball paradigm in 5 patients affected by unilateral thalamic hemorrhage. P3 latencies in these 5 patients were above the normal mean latency of age-matched controls +2/+3 S.D.s. The P3 delay was persistent in serial follow-ups at 6 months from stroke. Normal P3 latencies were instead recorded in 4 patients with paramedian hemorrhage not involving or only partially involving the thalamus.     

Changes in auditory P300 event-related potentials and brainstem evoked potentials in diabetes mellitus

To investigate the influence of diabetes mellitus on higher cognitive functions electrophysiologically, we studied auditory P300 event-related potentials (P300) in 40 NIDDM patients, taking into account wave I-V latencies (I-V) in auditory brainstem evoked potentials, clinical parameters and head MRI findings. Compared with 20 controls, diabetics had significantly longer P300 and I-V latencies. P300 latencies in diabetics correlated with neither I-V. HbA₁, blood glucose levels, nor disease duration. Of the 13 diabetics investigated neuroradiologically, four had lacunar infarcts with prolonged electrophysiological values. The remaining nine had normal MRI scans, but their physiological parameters were still significantly longer than those of controls. These findings suggest that NIDDM can independently alter higher cognitive and the central auditory pathway functions. Our data also suggest that these alterations occur regardless of the recent metabolic derangement and disease duration. Cerebrovascular ischemia, if present, also appears to contribute in part to cognitive alterations.     

Interpeak latency of auditory event-related potentials (P300) in senile depression and dementia of the Alzheimer type

Most studies on event-related potentials (ERP) in psychiatric illness or dementia have focused on the single-peak latency of ERP components. In the present study, not only peak latencies of ERP components (N1, P2, N2, and P3) but also interpeak latencies (IPL; N1-P2, P2-N2, and N2-P3) were analyzed using the auditory oddball task. Thirty-five senile depressed patients and 34 patients with dementia of the Alzheimer type (DAT) were compared to 39 age-matched healthy volunteers. The mean latencies of P2 and P3 were shorter in patients with senile depression than in controls. In DAT patients, the N2 and P3 latencies were longer. When the IPL was assessed, however, only the mean IPL of N1-P2 was shorter in patients with senile depression, while the P2-N2 IPL were longer in those with DAT. The IPL results suggest that in senile depression the early cognitive process is hastened and in DAT the middle process is disturbed. Based on these results, we conclude that IPL of the auditory ERP might be used to reveal the disturbed steps within the cognitive process.     

Prolonged latencies of the N2 and P3 of the auditory event-related potential in children at risk for schizophrenia

Summary In previous studies investigating long latency components of the event-related potential (ERP), schizophrenic patients generally showed reduced P3 amplitudes and in some studies prolonged N2 or P3 latencies. As there is a higher risk of offspring of schizophrenics than of mentally healthy parents developing this disease, the present study was intended to clarify whether ERP components (in particular the N2 and P3) differ between these two groups of children. Twelve high-risk and 12 age-matched control children (aged 9–16 years) performed an auditory oddball task in order to assess late ERP components. This task required the subject to covertly count rare target tone pips (P = 0.2) irregularly interspersed among frequent standard tone pips (P = 0.8) in two series of 400 pips. ERPs were recorded from midline electrodes (Fz, Cz, Pz). The results indicated distinctly prolonged N2 and P3 latencies in ERPs to target stimuli in children of schizophrenic patients. These findings suggest a slowed target classification in these children.     

双相障碍抑郁发作与单相抑郁症患者听觉事件相关电位P300的对照研究

目的:探讨双相障碍I型抑郁发作与单相抑郁患者听觉事件相关电位P300的差异及与各自临床特征相关性。方法:对60例双相障碍I型抑郁发作患者(双相组)、50例单相抑郁患者(单相组)以及50名正常对照者(对照组)进行P300检测;偏相关分析患者组P300与其临床特征及功能相关性。结果:患者组较对照组N1、P2、N2、P3a和P3b潜伏期显著延长(分别F=9.17,F=8.74,F=15.27,F=7.98,F=10.64;P均0.01);3组间N2-P3b潜伏期差异无统计学意义(F=0.46,P0.05);患者组较对照组N1、P2、N2、P3a、P3b和N2-P3b波幅显著降低(分别F=12.23,F=7.27,F=14.16,F=6.96,F=8.58,F=5.36;P均0.01);患者组较对照组按键反应时间显著延长(F=55.37,P0.01);单相组较双相组N1、N2波幅降低、N2潜伏期延长(P均0.05),双相组较单相组按键反应时间延长(P0.01)。双相组N1波幅与其HAMD评分负相关(P0.01),N2潜伏期与其HAMD评分正相关(P0.01),按键反应时间与其病程和HAMD评分正相关(P均0.05);单相组N2波幅与其HAMD评分负相关(P0.01),按键反应时间与其HAMD评分正相关(P0.05)。结论:双相障碍I型抑郁发作与单相抑郁患者听觉事件相关电位P300均存在异常,但损害有差异;P300异常在二者可能均为状态与素质性并存。     

Olfactory event-related potentials in normal subjects and patients with smell disorders.

We developed a device to record olfactory event-related potentials (OERP) from the human scalp. Methyl-cyclopentenolone was used as the odorant element. A total of 50 stimuli were delivered. Each stimulus lasted 0.5 sec and was delivered once every three inspirations. Normal OERPs were obtained with this device. The positive peak latencies were approximately 350 msec (P1) and 700 msec (P2), respectively. OERPs were also recorded in 40 patients with smell disorders. A positive response at about 300-400 msec was recorded in 7 patients (all females, 15-59 years old). The other 33 patients showed no response. The high potential area of this positive peak was located in the centro-occipital region of the scalp. The latency and the high potential area of this peak were similar to P1 recorded in normal subjects. The source of this peak was considered identical to that of P1. This may be a response to the trigeminal nerve during odor administration. P2 was not recorded in the patients with smell disorders. P2 may therefore be a response to the olfactory nerve.     

The N200 abnormalities of auditory event-related potentials in patients with panic disorder

Cognitive impairment in patients with panic disorder (PD) has been studied using event-related potentials (ERPs). However, previous studies obtained ERP data only at a few scalp sites, and seldom investigated N200 measurements from the difference waveforms. In the present study, auditory ERPs were recorded at 16 scalp sites during an active discrimination task of oddball paradigm. Fourteen PD patients (8 with agoraphobia; 6 without agoraphobia) were compared with 14 sex- and age-matched control subjects. For the nontarget waveforms, P2 amplitude was reduced in PD patients. For the target waveforms, a topographical difference between female PD patients and female controls was found for N200 amplitude, which attenuated in female PD patients over the parietal area. Two subcomponents of N200, N2a and N2b, were measured from the difference waveforms. A significant group difference was found for N2b amplitude, which reduced in PD patients compared with unaffected control subjects. It is suggested that N2b reduction reflects an abnormally controlled processing of stimulus information in PD.     

The effects of age on the N200 component of the auditory event-related potentials

This study was undertaken to determine the effects of development and aging on N200 of event-related potentials from childhood to adulthood. Event-related potentials were recorded from 164 normal subjects ranging in age from 4 to 77 years. A total of 127 of the 164 subjects demonstrated N200 peaks. N200 showed marked developmental changes. During childhood, the N200 latency decreased rapidly with age to the minimum (217±17.3 ms) at 16 years of age, while it was prolonged gradually with age during adulthood. The latency/age slope in the subjects from 5 to 15 years of age was -9.03 ms/year, while +0.97 ms/year in those from 16 to 77. The N200-P300 interpeak latency remained constant in all age groups and showed no age-related changes. The N200 amplitude decreased as age increased. Nineteen young cases showed N200 peaks to the frequent stimuli. Their ages ranged from 5 to 17 years. Our study suggests that N200 is valuable in evaluating the developmental and aging processes in the central nervous system. The results of this study could be used as normative data in clinical practices.     

The correlation between positive symptoms and left temporal event-related potentials in the P300 time window is auditory specific and training sensitive

One of the strongest correlations found between clinical symptoms and a biological index is that between the severity of positive symptoms of schizophrenia and the amplitude of the event-related potential (ERP) in the time window of the P300 deflection at left temporal scalp sites. The functional significance of the ERP component at stake is yet unknown. The present study aims at addressing this issue by testing whether or not the correlation a) is found in both the auditory and the visual modality, b) is restricted to the time window of the P300 deflection, and c) is stable over time. 12 patients suffering from schizophrenia were recorded 6 times at two month intervals in two oddball protocols, an auditory and a visual one. The correlation between the scores for the thought disturbance cluster of the PANSS (a cluster including most positive symptoms, i.e., conceptual disorganization, unusual thought content, grandiosity and hallucinations) and the P300 amplitude at left temporal sites was found 1) to occur only in the auditory modality, which, together with the late timing of the component, constrains its functional significance, 2) to appear in a time window adjacent to that of the P300 including at additional electrode sites, which would have to be confirmed by further studies, 3) to vanish along with the repetition of the recording sessions, which suggests that it is related to a processing difficulty that disappears with training.     

Auditory event-related potentials (P300) in epileptic patients.

Auditory event-related potentials (AERPs) were recorded during an auditory oddball paradigm in 108 epileptics and in 32 healthy controls. P300 latency varied in relationship with age only in controls. Symptomatic epileptics had significantly prolonged P300 mean latency compared to those without detectable brain lesion(s) on MR scan. Moreover, these latter patients were compared on the basis of epilepsy duration, type of seizure, seizure frequency and antiepileptic treatment; the application of a multiple regression model showed a significant relationship between P300 latency prolongation and epilepsy duration, seizure frequency and polytherapy.