Comprehensive analysis suggests simple processes underlying EEG/ERP - demonstration with the go/no-go paradigm in ADHD.

BACKGROUND: Current basic or more advanced methods for analysis of averaged EEG/ERP are based on assumptions on the underlying processes, which are not necessarily precise. NEW METHOD: In this work we present the findings of a method which obviates such assumptions and aims at a comprehensive analysis of the averaged EEG/ERP signal. RESULTS: For the sake of demonstration we chose the established go/no-go paradigm in the context of ADHD. Our analysis method characterized two spatiotemporally distinct neurophysiologic processes which underlie the sampled signal: one which may be related to attention and the other which may be more related to perception. COMPARISON WITH EXISTING METHOD(S): We show how these processes accord with and provide insight on the waveforms reported in the literature. CONCLUSIONS: Finally we suggest that application of our method on averaged EEG/ERP data sampled from other paradigms may point at a similarly parsimonious set of underlying neurophysiologic processes which underlie the signal.

Introducing a novel approach of network oriented analysis of ERPs, demonstrated on adult attention deficit hyperactivity disorder.

OBJECTIVE: Introducing a network-oriented analysis method (brain network activation [BNA]) of event related potential (ERP) activities and evaluating its value in the identification and severity-grading of adult ADHD patients. METHODS: Spatio-temporal interrelations and synchronicity of multi-sited ERP activity peaks were extracted in a group of 13 ADHD patients and 13 control subjects for the No-go stimulus in a Go/No-go task. Participants were scored by cross-validation against the most discriminative ensuing group patterns and scores were correlated to neuropsychological evaluation scores. RESULTS: A distinct frontal-central-parietal pattern in the delta frequency range, dominant at the P3 latency, was unraveled in controls, while central activity in the theta and alpha frequency ranges predominated in the ADHD pattern, involving early ERP components (P1-N1-P2-N2). Cross-validation based on this analysis yielded 92% specificity and 84% sensitivity and individual scores correlated well with behavioral assessments. CONCLUSIONS: These results suggest that the ADHD group was more characterized by the process of exerting attention in the early monitoring stages of the No-go signal while the controls were more characterized by the process of inhibiting the response to that signal. SIGNIFICANCE: The BNA method may provide both diagnostic and drug development tools for use in diverse neurological disorders.

The effects of subjectively significant stimuli on subsequent cognitive brain activity.

OBJECTIVE: To study brain activity modulation by preceding subjectively significant stimuli. Brain activity related to emotional and cognitive processing has been typically traced with fMRI's temporal resolution of seconds. In this study, the time course of activation in the brain areas involved was traced with millisecond temporal resolution. METHODS: Electrophysiological brain activity was recorded while 12 normal subjects performed an auditory cued attention task, with subjectively significant verbal distracters. Verbal distracters, administered at different times between the cue and the target in one third of the trials, were first names, whose subjective significance was individually assessed after the experiment using a validated questionnaire. Intracranial sources of scalp-recorded electrical activity were estimated and statistical comparisons were conducted to assess the effects and interactions of (1) cue validity; and (2) subjective significance of distracters, on brain activity evoked by the targets. RESULTS: Significant cue validity effects were found. Language-related areas were most involved following neutral distracters. Emotion-related areas were most involved following subjectively significant distracters. Thus, cue validity and distracter effects seem to have distinct effects. SIGNIFICANCE: The results indicate an effect of subjectively significant distracters on subsequent brain activity with an interaction between cognitive and emotional processes.

Time course of motor excitability before and after a task-related movement.

AIMS OF THE STUDY: The time course of motor excitability during a task-related unilateral right thumb movement was studied using sub-threshold transcranial magnetic stimulation (TMS) to the contralateral left motor cortex. The level of stimulation evoked a motor evoked potential (MEP) in the thumb when the subject was at rest in approximately 10% of the trials. METHODS: Subjects made a brief right thumb movement to the predictable omission of regularly presented tone bursts allowing experimental definition of TMS relative to the cue to move. Motor cortical excitability was characterized by amplitude and/or probability of eliciting MEPs. RESULTS: There were four periods of altered motor excitability during task performance compared to a control resting state: a first period of weak facilitation before movement between -500 to -200 ms, a second period without increased excitability approximately 150 ms before movement onset when MEPs amplitude was below that seen in rest, a third period of strong facilitation between -100 ms before movement and +200 ms after facilitation and a fourth period of weak facilitation between +200 to +500 ms. CONCLUSION: These results show that during performance of a task requiring a motor response, motor cortical excitability is increased above resting for hundreds of millisecond before and after the response, except for a transient period between 75 and 150 ms prior to movement onset. The temporal pattern of these excitability changes is compatible with multiple excitatory and inhibitory inputs interacting on motor cortex.

Preparatory slow potentials and event-related potentials in an auditory cued attention task.

OBJECTIVES: To examine reaction times and event-related potentials (ERPs) in an auditory cued attention task varying motor requirements, cue validity, and cue location. METHODS: Subjects (n=13) listened to cue-target stimulus pairs. Verbal cues (monaural, binaural) indicated the ear to receive a target tone 1.5s later. Cues correctly (valid) or incorrectly (invalid) predicted target ear, or were uninformative (neutral). In separate conditions subjects either responded by pressing one of two buttons, or did not respond to targets. ERPs for cues and targets (P50, N100, P200, late slow wave), and negative slow potentials between cues and targets were assessed. RESULTS: Target reaction times for valid cues were significantly shorter than for invalid cues, with intermediate values for neutral cues. When no motor response was required larger ERPs were seen to both cues and targets. Negative slow potentials had larger amplitudes before target presentation when subjects responded to targets; and were larger following neutral, vs. valid/invalid, cues. ERPs (N100, P200) to invalidly cued targets were significantly larger and a subsequent late slow wave was more positive, relative to validly cued targets. CONCLUSIONS: Expectancy for targets begins shortly after cue presentation, and is affected by both motor requirements and the information content of the cue. ERP amplitudes to targets are modulated by the correspondence between cue information and actual target location.

Echo suppression in the human cortex is affected by the spatial and temporal proximity of the primary sound and echo.

Echo suppression in the human auditory cortex was studied with auditory middle latency evoked potentials (AMEP) using virtual reality acoustic stimuli, including distance and elevation cues, presented by earphones. The purpose of the study was to assess the effect of proximity of the source sound and echo on the degree of echo suppression. Sixteen subjects were presented with source-echo pairs in which the preceding source sound was always at the vertex, and the echo varied among ten positions on the coronal plane. Positions varied in elevation, distance and time lag between source and echo. The psychoacoustic location judgment of the fused source-echo pair was closer to the source sound (more echo suppression) the nearer the echo drew to the source in its elevation and time. The equivalent dipole magnitudes of the cortical components of AMEP were significantly reduced (more suppression) with shorter echo lags and when echo elevation was similar to that of the source sound. The distances used in this study did not significantly affect echo suppression. These results indicate that echo suppression in the auditory cortex is more pronounced the closer are the primary sound and echo in locational attributes and timing. As source sound and echo draw apart, echo suppression in the cortex decreases and the perceived localization of the fused source-echo is more biased toward the echo.

Contribution of click frequency bands to the human binaural interaction components.

The purpose of this study was to determine the contribution of click frequency bands (broad-band, >2000 Hz, <2000 Hz and <1000 Hz) to binaural interaction components (BICs) of the human auditory brainstem evoked potentials (ABEPs). The human BICs were studied by subtracting the potentials to binaural clicks from the algebraic sum of monaurally evoked potentials to either ear. Effective frequency bands were derived using clicks alone or clicks with ipsilateral or binaural masking noise, high- or low-pass filtered at different cut-off frequencies. Analysis included single-channel vertex-cervical spinous process VII derivation of BIC and ABEP, as well as estimating the single, centrally located dipole equivalent of the surface activity from three orthogonally positioned electrode pairs, using the three-channel Lissajous' trajectory (3-CLT) analysis. All BIC 3-CLTs included three major components (labeled BdII, BeI, and BeII) approximately corresponding in latency to IIIn, V and VI ABEP peaks. All apex latencies of BIC 3-CLT, except BeI, were longer in response to <2000 Hz and <1000 Hz (low-frequency) effective clicks. Apex amplitude of components BeI and BeII of BIC 3-CLT were smaller with low-frequency effective clicks than with broad-band or high-frequency (>2000 Hz) clicks. We suggest that binaural interaction component BeI is mainly tuned to high frequencies, showing no frequency effect on latency, and decreasing in amplitude with decreasing click high frequency content. In contrast, BdII and BeII of the human BICs are evoked more synchronously by high-frequency binaural inputs, but are also sensitive to low frequencies, increasing in latency according to the cochleotopic activation pattern. These differences between BIC components may reflect their roles in sound localization.

Correlations between audiogram and objective hearing tests in sensorineural hearing loss.

Owing to its subjective nature, behavioral pure-tone audiometry often is an unreliable testing method in uncooperative subjects, and assessing the true hearing threshold becomes difficult. In such cases, objective tests are used for hearing-threshold determination (i.e., auditory brainstem evoked potentials [ABEP] and frequency-specific auditory evoked potentials: slow negative response at 10 msec [SN-10]). The purpose of this study was to evaluate the correlation between pure-tone audiogram shape and the predictive accuracy of SN-10 and ABEP in normal controls and in patients suffering from sensorineural hearing loss (SNHL). One-hundred-and-fifty subjects aged 15 to 70, some with normal hearing and the remainder with SNHL, were tested prospectively in a double-blind design. The battery of tests included pure-tone audiometry (air and bone conduction), speech reception threshold, ABEP, and SN-10. Patients with SNHL were divided into four categories according to audiogram shape (i.e., flat, ascending, descending, and all other shapes). The results showed that ABEP predicts behavioral thresholds at 3 kHz and 4 kHz in cases of high-frequency hearing loss. Also demonstrated was that ABEP threshold estimation at 3 kHz was not affected significantly by audiogram contour. A good correlation was observed between SN-10 and psychoacoustic thresholds at 1 kHz, the only exception being the group of subjects with ascending audiogram, in which SN-10 overestimated the hearing threshold.

Evidence for separate processing in the human brainstem of interaural intensity and temporal disparities for sound lateralization.

Sound lateralization can be induced by interaural intensity disparities (IIDs) or by interaural temporal disparities (ITDs). The purpose of this study was to indicate whether IIDs and ITDs are processed by the same central units that detect interaural disparity in timing of afferent activity. If sound lateralization to intensity and time cues was determined by the same afferent latency disparity detectors in the brainstem, lateralization would be the same, regardless of whether latency disparity was induced by IIDs or ITDs. Moreover, the disparity detectors, and thus their dipole equivalents, would be the same for equal lateralizations, whether induced by IIDs or ITDs. Auditory brainstem evoked potentials (ABEPs) were recorded in response to monaural and binaural clicks, with a variety of IIDs and ITDs. Peak II (proximal auditory nerve activity), peak III (input to the superior olivary complex), and binaural interaction components (BICs) BeI and BeII (binaurally activated upper pons) were identified and their latencies measured. The psychophysical lateralization of the clicks (in cm from vertex) was also measured in response to the same binaural stimuli. The correlations between interaural afferent latency disparities (difference in corresponding peak latencies originating in each ear) and psychophysical click lateralization were calculated. Similarly, the correlations with click lateralization of the BICs equivalent dipole latency as well as orientation change (relative to symmetrical clicks) were determined. A strong correlation with lateralization was found for peaks II and III latency disparities, with steeper slopes for IIDs than for ITDs. Moreover, binaural activity across the same lateralizations differed between IIDs and ITDs. These results, therefore, indicate that interaural time and intensity cues are processed by separate systems in the brainstem, both at the afferent convergence level and after interaural disparities are determined.

Evidence for spatio-topic organization of binaural processing in the human brainstem.

Three-channel Lissajous' trajectories (3-CLT) of the binaural interaction (BI) in auditory brainstem evoked potentials (ABEP) were derived from 13 normally and symmetrically hearing adults by subtracting the response to binaural clicks from the algebraic sum of monaural responses. ABEPs were recorded from four channels, three of them orthonormal to each other, in response to alternating polarity clicks, presented at a rate of 11/s with interaural time differences (ITD) of 0.2, 0.4 and 1.0 ms and an intensity of 65 dB nHL, or isochronic to both ears with interaural intensity differences (IIDs) of 5, 10 and 15 dB (65 dB nHL +/- 2.5, 5.0 and 7.5 dB, respectively). All 3-CLTs included 6 planar segments (labeled BdI, BdII, BdIII, BeI, BeII and Bf). Amplitudes of 3-CLT BI components were not significantly affected by increasing ITDs and IIDs, but latencies of all components increased significantly. The most remarkable finding was a significant change in apex orientations of BeI and BeII of the BI 3-CLT across stimulus conditions. The changes in BeI and BeII apex orientations, across stimulus conditions, may reflect differences in the anatomical representation of activity evoked by differently lateralized sounds. We suggest that this may indicate spatio-topic organization in the human brainstem.

Improved detection of auditory P3 abnormality in dementia using a variety of stimuli.

The purpose of this study was to test the improved sensitivity of P3 abnormality in the detection of dementia using a variety of auditory stimuli. Improved detection was obtained using auditory stimuli that differed in their cognitive attributes and by using several P3 measures. These measures included P3 latencies and amplitudes relative to pure tone evoked P3s. Fourteen demented patients (mean age 79.2 years) and a matched normative group were tested. Abnormality of P3 latency for pure tone targets was found in ten patients, equivalent to a hit-rate of 72%. The hit-rate could be further increased by using phonemically and phonetically different types of auditory stimuli, thought to vary in their cognitive attributes. These findings underscore the importance of using a variety of stimuli in testing demented patients.

Three-channel Lissajous' trajectory of the binaural interaction components of human auditory middle-latency evoked potentials.

Three-channel Lissajous' trajectories (3-CLTs) of the binaural interaction component (BI) of auditory middle latency evoked potentials (AMLEPs) were derived from 14 normally hearing adults by subtracting the response to binaural clicks from the algebraic sum of monaural responses. AMLEPs were recorded in response to 65 dB nHL, rarefaction clicks, presented at a rate of 3.3/s. A normative set of BI 3-CLT measures was calculated and compared with the corresponding measures of simultaneously recorded, single-channel vertex-left mastoid and vertex-neck derivations of BI and of AMLEP to binaural stimulation (B). 3-CLT measures included: apex latency, amplitude and orientation, as well as planar segment duration, orientation, size and shape. The results showed seven main apices and associated planar segments ('Be', 'Bf', 'Bg', 'Bh', 'Bi1', 'Bi2' and 'Bj') in the 3-CLT of BI. Apex latencies of the BI 3-CLT were comparable to peak latencies of the vertex-left mastoid and vertex-neck AMLEP and BI records, both in their absolute values and in intersubject variability. Durations of BI planar segments were approximately 5.0 ms. Apex amplitudes of BI 3-CLT were larger than the respective peak amplitudes of the vertex-mastoid and vertex-neck BI records, while their intersubject variabilities were comparable. The lateralization of BI components may indicate asymmetric processing of binaural auditory input, or may be connected with anatomical asymmetry such as skull thickness. Preliminary analyses did not reveal a clear correlation between the lateralization of the BI component 'Bi2' and the handedness of the subject. We suggest that BI components of AMLEP may be associated with the primary auditory cortex and subcortical ascending structures.

Absolute pitch--electrophysiological evidence.

People who have the ability to label or to produce notes without any reference are considered to possess Absolute Pitch (AP). Others, who need a reference in order to identify the notes, possess Relative Pitch (RP). The AP ability is assumed to reflect a unique, language-like representation of non-lexical musical notes in memory. The purpose of this study was to examine this assumption by comparing Event Related Potentials (ERP) of musicians with and without AP, to lexical and non-lexical representation of musical material. Subjects were eighteen young adult musicians. Seven were AP and eleven RP. Auditory stimuli, presented through earphones, were piano notes (non-lexical) or a voice saying the note's name (lexical). Visual stimuli, presented on a computer display were note symbols (non-lexical) or letters (lexical). Subjects performed a number of tasks, combining the two modalities (visual and auditory) and stimulus types (lexical and non-lexical), and reaction times (RT), performance accuracy and evoked potentials were recorded. The tasks forced the subjects to transfer mental representations of musical material from one mode to another. Our most important findings were the differences, between groups, in the scalp distribution of P300 amplitudes. We conclude that absolute pitch possessors use the same internal language as relative pitch possessors, when possible, but the distribution of the underlying brain activity is different between AP and RP subjects.

Temporal correspondence of intracranial, cochlear and scalp-recorded human auditory nerve action potentials.

Conventional, vertex-ipsilateral ear records ('A'), as well as 3-channel Lissajous' trajectories (3-CLTs) of auditory brain-stem evoked potentials (ABEPs) were recorded from the scalp simultaneously with tympanic membrane electrocochleograms ('TME') and auditory nerve compound action potentials ('8-AP') recorded intracranially using a wick electrode on the auditory nerve between the internal auditory meatus and the brain-stem. The recordings were made during surgical procedures exposing the auditory nerve. The peak latency recorded from 'TME' corresponded to trajectory amplitude peak 'a' of 3-CLT and to peak 'I' of the 'A' channel ABEP. Peak latency of '8-AP' was slightly longer than the latency of peak 'II' of 'A' when '8-AP' was recorded from the root entry zone and the same or shorter when recorded from the nerve trunk. '8-AP' peak latency was shorter than trajectory amplitude peak 'b' of 3-CLT regardless of where the wick electrode was along the nerve. Peak latencies from all recording sites clustered into two distinct groups--those that included N1 from 'TME,' peak 'I' of the 'A' record and trajectory amplitude peak 'a' of 3-CLT, and those that included the negative peak of '8-AP' and trajectory amplitude peak 'b' of 3-CLT, as well as peak 'II' of the 'A' record, when present. In one case, the latency of peak 'II' and trajectory amplitude peak 'b' was manipulated by changing the conductive properties of the medium surrounding the auditory nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Contralateral effects of cerebello-pontine angle exposure on human auditory brain-stem evoked potentials.

Auditory brain-stem evoked potentials (ABEPs) were recorded during surgical procedures which exposed the cerebello-pontine angle (CPA) in humans. Recordings made with the CPA contralateral to stimulus exposed were compared with those obtained with the skin sutured at the end of surgery. Single-channel as well as 3-channel Lissajous' trajectory (3-CLT) analyses were used to evaluate the effect of the surgical exposure on ABEP. The results suggest that exposure of the CPA contralateral to the stimulated ear did not affect dipole equivalent orientation nor magnitude, but did affect timing of the recorded activity being more pronounced for segments 'd'-'e' (corresponding to waves IV-V) than for 'a'-'b' (waves I-II). The results imply that the effects of disrupting the volume conductor may have been overwhelmed by other effects, such as local temperature changes. These changes, although not associated with clinical sequella, should be accounted for when analyzing subtle quantitative changes involving surgical exposures.

Auditory event-related potentials among dyslexic and normal-reading children: 3CLT and midline comparisons.

Event-related potentials (ERP's) to verbal and non-verbal auditory stimuli were recorded from normal-reading and from dyslexic children while performing a target-detection task ("oddball" paradigm). Two methods of analysis were used: (1) Peak latency and amplitude measures of P3 recorded from 3 midline electrodes; (2) P3 apex latency, amplitude and orientation in the three-channel Lissajous' trajectory (3CLT) derived from 3 orthogonal pairs of electrodes. P3 peak amplitude was significantly attenuated in dyslexic children compared to normal-reading children and in response to verbal stimuli compared to non-verbal stimuli. P3 apex latencies were longer and apex amplitudes larger in response to non-verbal compared to verbal stimuli. The most striking finding involved P3 apex orientation, which pointed in an upward-posterior direction with a slight tilt to the left among normal readers, but with a tilt to the right in dyslexics.

Applications of three-dimensional analysis to the auditory P300.

Auditory Event Related Potentials (ERPs) to target stimuli were recorded by three orthogonal derivations from 18 normal subjects and were represented in three dimensional voltage-space (3-D), to produce Three Channel Lissajous' Trajectories (3CLTs). Target stimuli differed by pitch, phonemic or phonetic attributes. Assuming a central location, the orientation of the equivalent dipole moment was calculated for specific points (apices) along the trajectories. The apices roughly corresponded to the P300 peak in a voltage/time representation. The 3-D analysis resulted ina dipole pointing in a posterior-upward direction close to the mid-sagittal plane. Based on anatomical measures coupled with the behavioral role of the limbic system, we propose that a major contribution to the P300 to the stimuli tested derives from the outflows of the hippocampus and amygdala, i.e. fornix and stria terminalis. Orientation and laterality of the P300 dipole demonstrated clinical sensitivity beyond that of latency and amplitude measures in voltage/time representations.

Brain potentials in a memory-scanning task. III. Potentials to the items being memorized.

Cerebral potentials evoked by items presented for memorization in a memory-scanning task were recorded from subjects ranging in age from 18 to 86 years old. Subjects were divided into younger (average age = 29 years) and older groups (average age = 66 years). Both verbal (digits) and non-verbal (musical notes) stimuli were used. Digits were presented in the auditory as well as the visual modality, and notes were presented acoustically. Potentials are described in terms of their scalp distribution, latency, and amplitude and are compared between the young and old subjects. Potentials evoked by the memorized items consisted of a positive (P50-90), negative (N100-150), positive (P185-225) sequence in the first 250 msec following stimulus onset. A sustained potential shift then followed whose amplitude differed with the items being memorized. The shift was positive in the parietal region being largest (5 microV) with verbal items presented visually and slightly smaller (3 microV) with non-verbal auditory stimuli (the notes); in contrast, verbal auditory digits were not associated with a detectable sustained parietal potential shift. In the frontal recordings there was a sustained potential shift accompanying all stimulus types, which was more negative in the young subjects. The amplitude of these sustained potential shifts differed as a function of the position of the item in the memorized set. These results provide electrophysiological evidence of brain activity during memorization that varies with the items being processed as well as differing between young and old subjects.

Brainstem auditory evoked potentials with increased stimulus rate in patients suffering from systemic lupus erythematosus.

Central nervous system involvement in systemic lupus erythematosus is frequently occult, may be the presenting sign, and is a bad prognostic indicator. At present, there is no reliable, sensitive laboratory test for the evaluation and diagnosis of subclinical central nervous system involvement of the disease. Brainstem auditory evoked potentials with and without increased stimulus rate have been used to diagnose ischemic lesions in the central nervous system. Brainstem auditory evoked potentials, with and without increased stimulus rate, was used to investigate 15 systemic lupus erythematosus patients, 20 normal participants, and 5 patients receiving corticosteroids for bronchial asthma. A significant statistical difference was found in the net effect of increased stimulus rate in comparisons of the systemic lupus erythematosus patients with the normal group. Brainstem auditory evoked potentials, with increased stimulus rate, demonstrated subclinical involvement of the central nervous system in systemic lupus erythematosus, reinforcing the notion that increased stimulus rate measures are sensitive to ischemic changes, in this case, even in neurologically asymptomatic patients.