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Abstract: Cues that involve a number of sensory modalities are processed in the brain in an interactive multimodal manner rather than independently for each modality. We studied multimodal integration in a natural, yet fully controlled scene, implemented as an interactive game in an auditory–haptic–visual virtual environment. In this imitation of a natural scene, the targets of perception were ecologically valid uni-, bi- and tri-modal manifestations of a simple event—a ball hitting a wall. Subjects were engaged in the game while their behavioral and early cortical electrophysiological responses were measured. Behavioral results confirmed that tri-modal cues were detected faster and more accurately than bi-modal cues, which, likewise, showed advantages over unimodal responses. Event-Related Potentials (ERPs) were recorded, and the first 200ms following stimulus onset was analyzed to reveal the latencies of cortical multimodal interactions as estimated by sLORETA. These electrophysiological findings indicated bi-modal as well as tri-modal interactions beginning very early (~30ms), uniquely for each multimodal combination. The results suggest that early cortical multimodal integration accelerates cortical activity and, in turn, enhances performance measures. This acceleration registers on the scalp as sub-additive cortical activation. [Copyright &y& Elsevier]

Abstract: Objective: To define the brain activity involved in impaired response inhibition of Attention Deficit Hyperactivity Disorder (ADHD) in adults. Methods: Performance measures and brain activity of 14 adult ADHD subjects and 14 controls, matched for age, gender, and overall intelligence were compared in an auditory Go–NoGo paradigm to tones. The task required a button press (Go) to 80% and inhibition of response (NoGo) to 20% of the tones, according to the tone’s pitch. Results: In NoGo trials ADHD subjects made significantly more commission errors compared to controls. ERPs of ADHD subjects showed smaller amplitudes of P3 (but not N2), and longer latencies of both N2 and P3. Source current density estimation revealed reduced activity in the right frontal dorsolateral cortex and in the posterior cingulate of the ADHD group. In addition, ADHD subjects showed an unexpected significantly enhanced response inhibition in Go trials, with excessive omission errors associated with significantly larger N2 amplitudes. Conclusion: In ADHD the neural networks sub-serving response inhibition are impaired. Significance: ADHD is a general dis-regulation of behavioral inhibition, not limited to response inhibition. [Copyright &y& Elsevier]

Abstract: Objective: The combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been hampered by the large artifact that the TMS generates in the EEG. Using TMS with EEG necessitates a sophisticated artifact-resistant EEG system that can acquire reliable signals in the crucial several tens of milliseconds immediately following the TMS pulse. Here, we demonstrate the use of a novel artifact removal algorithm together with a 24-bit EEG system to achieve similar recordings as those obtained with the dedicated TMS-compatible EEG system. Methods: This setup was used to compare TMS-evoked responses between a group of healthy controls and a group of patients with schizophrenia, a condition in which effective neural connectivity is thought to be compromised. Results: We observe differences in TMS-evoked responses between the two groups, similar to those recently reported in a study that used a dedicated TMS-compatible EEG system. Conclusions: The standard 24-bit EEG system combined with an artifact removal algorithm produces results similar to the dedicated TMS-compatible system. Significance: This paves the way for more researchers and clinicians to use TMS-evoked responses for research and diagnosis of a wide spectrum of disorders. [Copyright &y& Elsevier]

The authors used a semantic priming paradigm to investigate the distractibility phenomenon of patients with frontal lobe lesions (FLPs). They tested two disractibility categories: an inhibition category requiring inhibition of an automatic response and a unexpected stimuli. Fifteen FLPs were compared with 2 mathed control groups: 14 posterior-lesion patients and 15 normal controls. Both behavioral and event-related brain potential (ERP) measures were used. The results suggest that, although there were differences in performance between the FLP group and the control groups, there was no evidence that the FLPs had difficulty specifically with the inhibition category. The most consistent ERP result was that the FLP group had longer N100 latencies than either control group. On the basis of these results, the authors hypothesize that FLPs have difficulty focusing on and starting to process a new stimulus. The authors also discuss the unique contribution ERP evidence has made to cognitive studies. [ABSTRACT FROM AUTHOR]

ABSTRACT. The selectivity of frontal lobe lesion effects in the domains of verbal-information processing has not been well established. The authors hypothesized that capacity-limited controlled processing would be more impaired than automatic processing in frontal lobe patients (FLPs). Fifteen FLPs were compared with 2 matched control groups: 14 posterior-lesion patients and 15 normal controls. Both behavioral and event-related brain potential (ERP) measures were collected. Results suggest that both automatic and controlled processing were affected by frontal lobe lesions. ERP results indicated that the main difficulty for the FLPs was in the perceptual stage of information processing. This rather unexpected result may be explained by a basic difficulty of FLPs in attending to a new stimulus in order to process it. [ABSTRACT FROM AUTHOR]

Steady-state evoked potentials (SSEP) are the electrical activity recorded from the scalp in response to high-rate sensory stimulation. SSEP consist of a constituent frequency component matching the stimulation rate, whose amplitude and phase remain constant with time and are sensitive to functional changes in the stimulated sensory system. Monitoring SSEP during neurosurgical procedures allows identification of an emerging impairment early enough before the damage becomes permanent. In routine practice, SSEP are extracted by averaging of the EEG recordings, allowing detection of neurological changes within approximately a minute. As an alternative to the relatively slow-responding empirical averaging, we present an algorithm that detects changes in the SSEP within seconds. Our system alerts when changes in the SSEP are detected by applying a two-step Generalized Likelihood Ratio Test (GLRT) on the unaveraged EEG recordings. This approach outperforms conventional detection and provides the monitor with a statistical measure of the likelihood that a change occurred, thus enhancing its sensitivity and reliability. The system's performance is analyzed using Monte Carlo simulations and tested on real EEG data recorded under coma. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Auditory cortical N100s were examined in ten auditory neuropathy (AN) subjects as objective measures of impaired hearing. Methods: Latencies and amplitudes of N100 in AN to increases of frequency (4–50%) or intensity (4–8dB) of low (250Hz) or high (4000Hz) frequency tones were compared with results from normal-hearing controls. The sites of auditory nerve dysfunction were pre-synaptic (n =3) due to otoferlin mutations causing temperature sensitive deafness, post-synaptic (n =4) affecting other cranial and/or peripheral neuropathies, and undefined (n =3). Results: AN consistently had N100s only to the largest changes of frequency or intensity whereas controls consistently had N100s to all but the smallest frequency and intensity changes. N100 latency in AN was significantly delayed compared to controls, more so for 250 than for 4000Hz and more so for changes of intensity compared to frequency. N100 amplitudes to frequency change were significantly reduced in ANs compared to controls, except for pre-synaptic AN in whom amplitudes were greater than controls. N100 latency to frequency change of 250 but not of 4000Hz was significantly related to speech perception scores. Conclusions: As a group, AN subjects’ N100 potentials were abnormally delayed and smaller, particularly for low frequency. The extent of these abnormalities differed between pre- and post-synaptic forms of the disorder. Significance: Abnormalities of auditory cortical N100 in AN reflect disorders of both temporal processing (low frequency) and neural adaptation (high frequency). Auditory N100 latency to the low frequency provides an objective measure of the degree of impaired speech perception in AN. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To examine auditory cortical potentials in normal-hearing subjects to intensity increments in a continuous pure tone at low, mid, and high frequency. Methods: Electrical scalp potentials were recorded in response to randomly occurring 100ms intensity increments of continuous 250, 1000, and 4000Hz tones every 1.4s. The magnitude of intensity change varied between 0, 2, 4, 6, and 8dB above the 80dB SPL continuous tone. Results: Potentials included N100, P200, and a slow negative (SN) wave. N100 latencies were delayed whereas amplitudes were not affected for 250Hz compared to 1000 and 4000Hz. Functions relating the magnitude of the intensity change and N100 latency/amplitude did not differ in their slope among the three frequencies. No consistent relationship between intensity increment and SN was observed. Cortical dipole sources for N100 did not differ in location or orientation between the three frequencies. Conclusions: The relationship between intensity increments and N100 latency/amplitude did not differ between tonal frequencies. A cortical tonotopic arrangement was not observed for intensity increments. Our results are in contrast to prior studies of brain activities to brief frequency changes showing cortical tonotopic organization. Significance: These results suggest that intensity and frequency discrimination employ distinct central processes. [Copyright &y& Elsevier]

Abstract: Objective: We examined auditory cortical potentials in normal hearing subjects to spectral changes in continuous low and high frequency pure tones. Methods: Cortical potentials were recorded to increments of frequency from continuous 250 or 4000Hz tones. The magnitude of change was random and varied from 0% to 50% above the base frequency. Results: Potentials consisted of N100, P200 and a slow negative wave (SN). N100 amplitude, latency and dipole magnitude with frequency increments were significantly greater for low compared to high frequencies. Dipole amplitudes were greater in the right than left hemisphere for both base frequencies. The SN amplitude to frequency changes between 4% and 50% was not significantly related to the magnitude of spectral change. Conclusions: Modulation of N100 amplitude and latency elicited by spectral change is more pronounced with low compared to high frequencies. Significance: These data provide electrophysiological evidence that central processing of spectral changes in the cortex differs for low and high frequencies. Some of these differences may be related to both temporal- and spectral-based coding at the auditory periphery. Central representation of frequency change may be related to the different temporal windows of integration across frequencies. [Copyright &y& Elsevier]

Abstract: Analyzing the brain responses to transcranial magnetic stimulation (TMS) using electroencephalography (EEG) is a promising method for the assessment of functional cortical connectivity and excitability of areas accessible to this stimulation. However, until now it has been difficult to analyze the EEG responses during the several tens of milliseconds immediately following the stimulus due to TMS-induced artifacts. In the present study we show that by combining a specially adapted recording system with software artifact correction it is possible to remove a major part of the artifact and analyze the cortical responses as early as 10 ms after TMS. We used this methodology to examine responses of left and right primary motor cortex (M1) to TMS at different intensities. Based on the artifact-corrected data we propose a model for the cortical activation following M1 stimulation. The model revealed the same basic response sequence for both hemispheres. A large part of the response could be accounted for by two sources: a source close to the stimulation site (peaking ∼15 ms after the stimulus) and a midline frontal source ipsilateral to the stimulus (peaking ∼25 ms). In addition the model suggests responses in ipsilateral temporo-parietal junction areas (∼35 ms) and ipsilateral (∼30 ms) and middle (∼50 ms) cerebellum. Statistical analysis revealed significant dependence on stimulation intensity for the ipsilateral midline frontal source. The methodology developed in the present study paves the way for the detailed study of early responses to TMS in a wide variety of brain areas. [Copyright &y& Elsevier]

Paired associative stimulation (PAS), which combines repetitive peripheral nerve stimulation with transcranial magnetic stimulation (TMS), may induce neuroplastic changes in somatosensory cortex (S1), possibly by long-term potentiation-like mechanisms. We used multichannel median nerve somatosensory evoked potential (MN-SSEP) recordings and two-point tactile discrimination testing to examine the location and behavioural significance of these changes. When TMS was applied to S1 near-synchronously to an afferent signal containing mechanoreceptive information, MN-SSEP changes (significant at 21–31 ms) could be explained by a change in a tangential source located in Brodmann area 3b, with their timing and polarity suggesting modification of upper cortical layers. PAS-induced MN-SSEP changes between 28 and 32 ms were linearly correlated with changes in tactile discrimination. Conversely, when the near-synchronous afferent signal contained predominantly proprioceptive information, PAS-induced MN-SSEP changes (20–29 ms) were shifted medially, and tactile performance remained stable. With near-synchronous mechanoreceptive stimulation subtle differences in the timing of the two interacting signals tended to influence the direction of tactile performance changes. PAS performed with TMS delivered asynchronously to the afferent pulse did not change MN-SSEPs. Hebbian interaction of mechanoreceptive afferent signals with TMS-evoked activity may modify synaptic efficacy in superficial cortical layers of Brodmann area 3b and is associated with timing-dependent and qualitatively congruent behavioural changes. [ABSTRACT FROM AUTHOR]

This article describes a positive experience in building Arab and Israeli cooperation through health initiatives. Over the past 10 years Israeli, Jordanian, and Palestinian health professionals have worked together through the Canada International Scientific Exchange Program (CISEPO). In the initial project, nearly 17 000 Arab and Israeli newborn babies were tested for early detection of hearing loss, an important health issue for the region. The network has grown to address additional needs, including mother-child health, nutrition, infectious diseases, and youth health. Our guiding model emphasises two goals: project-specific outcomes in health improvement, and broader effects on cross-border cooperation. Lessons learned from this experience and the model provide direction for ways that health professionals can contribute to peacebuilding. [ABSTRACT FROM AUTHOR]

Objective: Mu and beta EEG oscillations show typical desynchronization patterns during movement. The aim of the current study was to assess whether in sub-acute stroke patients the magnitude of movement-related desynchronization reflects the extent of residual motor ability in the paretic upper limb., Methods: EEG and EMG data were recorded from 14 first-event stroke patients during repeated wrist extension movements of the paretic upper limb. Residual motor ability was assessed by the Fugl Meyer and Box and Blocks standardized clinical tests. Normalized lesion data was analyzed using the MEDx software., Results: The magnitude of event-related de-synchronization (ERD) of the high-mu and low-beta bands of the EEG, measured over the affected hemisphere, correlated significantly with (a) residual motor function in the paretic upper limb as measured by standard clinical tests; (b) the magnitude of EMG recorded from the paretic upper limb during wrist extension; and (c) the total hemispheric volume loss (negative correlation)., Conclusion: The magnitude of high-mu and low-beta ERD recorded from the lesioned hemisphere of subacute stroke patients correlates with residual motor ability in the paretic upper limb., Significance: Measures derived from quantitative EEG analysis may play an important role in neurorehabilitation clinical practice., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Physicians caring for children with serious acute neurologic disease must process overwhelming amounts of physiological and medical information. Strategies to optimize real time display of this information are understudied., Objectives: Our goal was to engage clinical and engineering experts to develop guiding principles for creating a pediatric neurology intensive care unit (neuroPICU) monitor that integrates and displays data from multiple sources in an intuitive and informative manner., Methods: To accomplish this goal, an international group of physicians and engineers communicated regularly for one year. We integrated findings from clinical observations, interviews, a survey, signal processing, and visualization exercises to develop a concept for a neuroPICU display., Results: Key conclusions from our efforts include: (1) A neuroPICU display should support (a) rapid review of retrospective time series (i.e. cardiac, pulmonary, and neurologic physiology data), (b) rapidly modifiable formats for viewing that data according to the specialty of the reviewer, and (c) communication of the degree of risk of clinical decline. (2) Specialized visualizations of physiologic parameters can highlight abnormalities in multivariable temporal data. Examples include 3-D stacked spider plots and color coded time series plots. (3) Visual summaries of EEG with spectral tools (i.e. hemispheric asymmetry and median power) can highlight seizures via patient-specific "fingerprints." (4) Intuitive displays should emphasize subsets of physiology and processed EEG data to provide a rapid gestalt of the current status and medical stability of a patient., Conclusions: A well-designed neuroPICU display must present multiple datasets in dynamic, flexible, and informative views to accommodate clinicians from multiple disciplines in a variety of clinical scenarios.

This study determined the effects of phonology and semantics on the distribution of cortical activity to the second of a pair of words in first and second language (mixed pairs). The effects of relative proficiency in the two languages and linguistic setting (monolinguistic or mixed) are reported in a companion paper. Ten early bilinguals and 14 late bilinguals listened to mixed pairs of words in Arabic (L1) and Hebrew (L2) and indicated whether both words in the pair had the same or different meanings. The spatio-temporal distribution of current densities of event-related potentials were estimated for each language and according to semantic and phonologic relationship (same or different) compared with the first word in the pair. During early processing (<300 ms), brain activity in temporal and temporoparietal auditory areas was enhanced by phonologic incongruence between words in the pair and in Wernicke's area by both phonologic and semantic priming. In contrast, brain activities during late processing (>300 ms) were enhanced by semantic incongruence between the two words, particularly in temporal areas and in left hemisphere Broca's and Wernicke's areas. The latter differences were greater when words were in L2. Surprisingly, no significant effects of relative proficiency on processing the second word in the pair were found. These results indicate that the distribution of brain activity to the second of two words presented bilingually is affected differently during early and late processing by both semantic and phonologic priming by- and incongruence with the immediately preceding word., (Copyright © 2012 Wiley Periodicals, Inc.)

The study determined how spatiotemporal distribution of cortical activity to words in first and second language is affected by language, proficiency, and linguistic setting. Ten early bilinguals and 14 late adult bilinguals listened to pairs of words presented in Arabic (L1), Hebrew (L2), or in mixed pairs and indicated whether both words had the same meaning or not. Source current densities of event-related potentials were estimated. Activity to first words in the pair lateralized to right hemisphere, higher to L1 than L2 during early processing (<300 ms) among both groups but only among late bilinguals during late processing (>300 ms). During early and late processing, activities were larger in mixed than monolinguistic settings among early bilinguals but lower in mixed than in monolinguistic settings among late bilinguals. Late processing in auditory regions was of larger magnitude in left than right hemispheres among both groups. Activity to second words in the pair was larger in mixed than in monolinguistic settings during both early and late processing among both groups. Early processing of second words in auditory regions lateralized to the right among early bilinguals and to the left among late bilinguals, whereas late processing did not differ between groups. Wernicke's area activity during late processing of L2 was larger on the right, while on the left no significant differences between languages were found. The results show that cortical language processing in bilinguals differs between early and late processing and these differences are modulated by linguistic proficiency and setting., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: Compare brain potentials to consonant vowels (CVs) as a function of both voice onset times (VOTs) and consonant position; initial (CV) versus second (VCV)., Methods: Auditory cortical potentials (N100, P200, N200, and a late slow negativity, (SN) were recorded from scalp electrodes in twelve normal hearing subjects to consonant vowels in initial position (CVs: /du/ and /tu/), in second position (VCVs: /udu/ and /utu/), and to vowels alone (V: /u/) and paired (VVs: /uu/) separated in time to simulate consonant voice onset times (VOTs)., Results: CVs evoked "acoustic onset" N100s of similar latency but larger amplitudes to /du/ than /tu/. CVs preceded by a vowel (VCVs) evoked "acoustic change" N100s with longer latencies to /utu/ than /udu/. Their absolute latency difference was less than the corresponding VOT difference. The SN following N100 to VCVs was larger to /utu/ than /udu/. Paired vowels (/uu/) separated by intervals corresponding to consonant VOTs evoked N100s with latency differences equal to the simulated VOT differences and SNs of similar amplitudes. Noise masking resulted in VCV N100 latency differences that were now equal to consonant VOT differences. Brain activations by CVs, VCVs, and VVs were maximal in right temporal lobe., Conclusion: Auditory cortical activities to CVs are sensitive to: (1) position of the CV in the utterance; (2) VOTs of consonants; and (3) noise masking., Significance: VOTs of stop consonants affect auditory cortical activities differently as a function of the position of the consonant in the utterance., (Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Pseudobulbar affect (PBA) consists of uncontrollable outbursts of laughter or crying inappropriate to the patient's external circumstances and incongruent with the patient's internal emotional state. Recent data suggest disruption of cortico-pontine-cerebellar circuits, reducing the threshold for motor expression of emotion. Disruption of the microcircuitry of the cerebellum itself may likewise impair its ability to act as a gate-control for emotional expression. Current evidence also suggests that serotonergic and glutamatergic neurotransmission play key roles. Although antidepressants have shown benefit, the supportive clinical data have often derived from small numbers of patients and unvalidated measures of PBA severity. Dextromethorphan/quinidine, the first FDA-approved PBA medication, is a novel therapy with antiglutamatergic actions. As life expectancy lengthens and the neurologic settings of PBA become more common, the need for treatment can be expected to increase.

The purpose of this study was to compare cortical brain responses evoked by amplitude modulated acoustic beats of 3 and 6 Hz in tones of 250 and 1000 Hz with those evoked by their binaural beats counterparts in unmodulated tones to indicate whether the cortical processes involved differ. Event-related potentials (ERPs) were recorded to 3- and 6-Hz acoustic and binaural beats in 2000 ms duration 250 and 1000 Hz tones presented with approximately 1 s intervals. Latency, amplitude and source current density estimates of ERP components to beats-evoked oscillations were determined and compared across beat types, beat frequencies and base (carrier) frequencies. All stimuli evoked tone-onset components followed by oscillations corresponding to the beat frequency, and a subsequent tone-offset complex. Beats-evoked oscillations were higher in amplitude in response to acoustic than to binaural beats, to 250 than to 1000 Hz base frequency and to 3 Hz than to 6 Hz beat frequency. Sources of the beats-evoked oscillations across all stimulus conditions located mostly to left temporal lobe areas. Differences between estimated sources of potentials to acoustic and binaural beats were not significant. The perceptions of binaural beats involve cortical activity that is not different than acoustic beats in distribution and in the effects of beat- and base frequency, indicating similar cortical processing., (Copyright 2010 Elsevier B.V. All rights reserved.)

Objective: To define brain activity corresponding to an auditory illusion of 3 and 6Hz binaural beats in 250Hz or 1000Hz base frequencies, and compare it to the sound onset response., Methods: Event-Related Potentials (ERPs) were recorded in response to unmodulated tones of 250 or 1000Hz to one ear and 3 or 6Hz higher to the other, creating an illusion of amplitude modulations (beats) of 3Hz and 6Hz, in base frequencies of 250Hz and 1000Hz. Tones were 2000ms in duration and presented with approximately 1s intervals. Latency, amplitude and source current density estimates of ERP components to tone onset and subsequent beats-evoked oscillations were determined and compared across beat frequencies with both base frequencies., Results: All stimuli evoked tone-onset P(50), N(100) and P(200) components followed by oscillations corresponding to the beat frequency, and a subsequent tone-offset complex. Beats-evoked oscillations were higher in amplitude with the low base frequency and to the low beat frequency. Sources of the beats-evoked oscillations across all stimulus conditions located mostly to left lateral and inferior temporal lobe areas in all stimulus conditions. Onset-evoked components were not different across stimulus conditions; P(50) had significantly different sources than the beats-evoked oscillations; and N(100) and P(200) sources located to the same temporal lobe regions as beats-evoked oscillations, but were bilateral and also included frontal and parietal contributions., Conclusions: Neural activity with slightly different volley frequencies from left and right ear converges and interacts in the central auditory brainstem pathways to generate beats of neural activity to modulate activities in the left temporal lobe, giving rise to the illusion of binaural beats. Cortical potentials recorded to binaural beats are distinct from onset responses., Significance: Brain activity corresponding to an auditory illusion of low frequency beats can be recorded from the scalp.

Objective: To define cortical brain responses to large and small frequency changes (increase and decrease) of high- and low-frequency tones., Methods: Event-Related Potentials (ERPs) were recorded in response to a 10% or a 50% frequency increase from 250 or 4000 Hz tones that were approximately 3 s in duration and presented at 500-ms intervals. Frequency increase was followed after 1 s by a decrease back to base frequency. Frequency changes occurred at least 1 s before or after tone onset or offset, respectively. Subjects were not attending to the stimuli. Latency, amplitude and source current density estimates of ERPs were compared across frequency changes., Results: All frequency changes evoked components P(50), N(100), and P(200). N(100) and P(200) had double peaks at bilateral and right temporal sites, respectively. These components were followed by a slow negativity (SN). The constituents of N(100) were predominantly localized to temporo-parietal auditory areas. The potentials and their intracranial distributions were affected by both base frequency (larger potentials to low frequency) and direction of change (larger potentials to increase than decrease), as well as by change magnitude (larger potentials to larger change). The differences between frequency increase and decrease depended on base frequency (smaller difference to high frequency) and were localized to frontal areas., Conclusions: Brain activity varies according to frequency change direction and magnitude as well as base frequency., Significance: The effects of base frequency and direction of change may reflect brain networks involved in more complex processing such as speech that are differentially sensitive to frequency modulations of high (consonant discrimination) and low (vowels and prosody) frequencies.

Purpose: To characterize the brain activity and associated cortical structures involved in pseudobulbar affect (PBA), a condition characterized by uncontrollable episodes of emotional lability in patients with multiple sclerosis (MS)., Methods: Behavioral responses and event related potentials (ERP) in response to subjectively significant and neutral verbal stimuli were recorded from 33 subjects in 3 groups: 1) MS patients with PBA (MS+PBA); 2) MS patients without PBA (MS); 3) Healthy control subjects (HC). Statistical non-parametric mapping comparisons of ERP source current density distributions between groups were conducted separately for subjectively significant and for neutral stimuli., Results: Behavioral responses showed more impulsive performance in patients with PBA. As expected, almost all ERP waveform comparisons between the MS groups and controls were significant. Source analysis indicated significantly distinct activation in MS+PBA in the vicinity of the somatosensory and motor areas in response to neutral stimuli, and at pre-motor and supplementary motor areas in response to subjectively significant stimuli. Both subjectively significant and neutral stimuli evoked higher current density in MS+PBA compared to both other groups., Conclusions: PBA of MS patients involves cortical structures related to sensory-motor and emotional processing, in addition to overactive involvement of motor cortical areas in response to neutral stimuli., Significance: These results may suggest that a 'disinhibition' of a "gate control"-type mechanism for emotional expression may lead to the lower emotional expression threshold of pseudobulbar affect.

Two types of perceptual visual grouping, differing in complexity of shape formation, were examined under inattention. Fourteen participants performed a similarity judgment task concerning two successive briefly presented central targets surrounded by task-irrelevant simple and complex grouping patterns. Event-related potentials (ERPs) were recorded from 22 scalp electrodes and source current density estimations were conducted for the net response to the task-irrelevant background patterns, using low-resolution electromagnetic tomography (LORETA). Although participants' subjective reports indicated that neither type of organization induced awareness, electrophysiological results showed they both evoked significant activation in occipital, parieto-temporal and frontal brain areas. Behavioral results demonstrated that only grouping of the simple pattern arose under inattention. In contrast to the complex pattern, the processing of the simple pattern was associated with an initially longer latency and higher activation beginning at 130 ms. These results support the distinction of grouping patterns differing in complexity of shape formation.

Objective: The auditory Event-Related Potentials (ERP) of component P50 to sound onset and offset have been reported to be similar, but their magnetic homologue has been reported absent to sound offset. We compared the spatio-temporal distribution of cortical activity during P50 to sound onset and offset, without confounds of spectral change., Methods: ERPs were recorded in response to onsets and offsets of silent intervals of 0.5 s (gaps) appearing randomly in otherwise continuous white noise and compared to ERPs to randomly distributed click pairs with half second separation presented in silence. Subjects were awake and distracted from the stimuli by reading a complicated text. Measures of P50 included peak latency and amplitude, as well as source current density estimates to the clicks and sound onsets and offsets., Results: P50 occurred in response to noise onsets and to clicks, while to noise offset it was absent. Latency of P50 was similar to noise onset (56 ms) and to clicks (53 ms). Sources of P50 to noise onsets and clicks included bilateral superior parietal areas. In contrast, noise offsets activated left inferior temporal and occipital areas at the time of P50. Source current density was significantly higher to noise onset than offset in the vicinity of the temporo-parietal junction., Conclusions: P50 to sound offset is absent compared to the distinct P50 to sound onset and to clicks, at different intracranial sources. P50 to stimulus onset and to clicks appears to reflect preattentive arousal by a new sound in the scene. Sound offset does not involve a new sound and hence the absent P50., Significance: Stimulus onset activates distinct early cortical processes that are absent to offset.

Objective: To study the effects of duration and intensity of noise that precedes gaps in noise on the N-Complex (N(1a) and N(1b)) of Event-Related Potentials (ERPs) to the gaps., Methods: ERPs were recorded from 13 normal subjects in response to 20 ms gaps in 2-4.5 s segments of binaural white noise. Within each segment, the gaps appeared after 500, 1500, 2500 or 4000 ms of noise. Noise intensity was either 75, 60 or 45 dBnHL. Analysis included waveform peak measurements and intracranial source current density estimations, as well as statistical assessment of the effects of pre-gap noise duration and intensity on N(1a) and N(1b) and their estimated intracranial source activity., Results: The N-Complex was detected at about 100 ms under all stimulus conditions. Latencies of N(1a) (at approximately 90 ms) and N(1b) (at approximately 150 ms) were significantly affected by duration of the preceding noise. Both their amplitudes and the latency of N(1b) were affected by the preceding noise intensity. Source current density was most prominent, under all stimulus conditions, in the vicinity of the temporo-parietal junction, with the first peak (N(1a)) lateralized to the left hemisphere and the second peak (N(1b)) - to the right. Additional sources with lower current density were more anterior, with a single peak spanning the duration of the N-Complex., Conclusions: The N(1a) and N(1b) of the N-Complex of the ERPs to gaps in noise are affected by both duration and intensity of the pre-gap noise. The minimum noise duration required for the appearance of a double-peaked N-Complex is just under 500 ms, depending on noise intensity. N(1a) and N(1b) of the N-Complex are generated predominantly in opposite temporo-parietal brain areas: N(1a) on the left and N(1b) on the right., Significance: Duration and intensity interact to define the dual peaked N-Complex, signaling the cessation of an ongoing sound.

Objective: To indicate whether the double peaked N(1) to gaps in continuous white noise is a composite of onset and offset responses to transients or whether it reflects higher processing such as change or mismatch detection and to assess the role of attention in this process., Methods: Evoked potentials were recorded to two binaural stimulus types: (1) gaps of different durations randomly distributed in continuous white noise; and (2) click pairs at intervals identical to those between gap onsets and offsets in the continuous noise stimulus. Potentials to these stimuli were recorded while subjects read a text and while detecting gaps in noise or click pairs., Results: Potentials were detected to all click pairs and to gaps of 5 ms or longer, corresponding to the subjects' psychoacoustic gap detection threshold. With long gap durations of 200-800 ms, distinct potentials to gap onset and gap offset were observed. The waveforms to all click pairs and to offsets of long gaps were similar and single-peaked, while potentials to gaps of 10 ms and longer, and potentials to onsets of long gaps were double-peaked, consisting of two N(1) negativities, 60 ms apart, irrespective of gap duration. The first (N(1a)), was more frontal in its distribution and similar to that of clicks. The second (N(1b)) peak's distribution was more central/temporal and its source locations and time course of activity were distinct. No effects of attention on any of the varieties and constituents of N(1) were observed., Conclusions: Comparing potentials to gap onsets, to click pairs and to gap offsets, suggests that potentials to gap onsets involve not only sound onset/offset responses (N(1), N(1a)) but also the subsequent pre-attentive perception of the cessation of an ongoing sound (N(1b)). We propose that N(1b) is distinct from change or mismatch detection and is associated with termination of an ongoing continuous stimulus. We propose to call it the N(egation)-process., Significance: A constituent of the N(1) complex is shown to be associated with the pre-attentive perception of termination of an ongoing stimulus and to have distinct scalp distribution and intracranial sources.

Objective: To determine the generality of auditory processing impairment in phonologic dyslexics by studying their auditory Event-Related Potentials (ERPs) and the spatio-temporal distribution of their brain activity to auditory linguistic and non-linguistic stimuli with temporal and spectral discriminating cues., Methods: Fourteen adult phonologic dyslexics and 14 normal reading students, all with high academic achievements, were compared. ERP waveform analysis and current density source estimation (Low resolution Electromagnetic Tomographic Analysis-LORETA) were conducted on 21-channel records from subjects who passively listened or actively discriminated 4 types of auditory stimuli: linguistic and non-linguistic stimuli that differed in spectral or temporal characteristics., Results: Significant differences were found for all ERP latencies (N1, P2, N2, P3) in response to all stimuli, with dyslexics presenting longer latencies compared to normal readers. Current density distributions and their time courses also differed significantly, regardless of stimulus type or attention allocation. Among normal readers, early activity (around N1) was characterized by a rapid change of maximum activity from right to left temporal lobe. Later activity (around P3) was characterized by a stable temporal activity with bilaterally synchronous peak activity. Among the dyslexics, the early N1 activity was stable with left hemisphere prominence, with no alternation between the hemispheres, while the later P3 activity peaked earlier in the right hemisphere than in the left., Conclusions: Dyslexics were different from controls in processing all auditory stimuli: verbal and non-verbal stimuli with temporal as well as with spectral discriminating cues. The differences mainly consisted of latency and time courses of current density distributions, beginning as early as N1 and extending to the late P3., Significance: Differences in processing auditory stimuli by phonologic dyslexics are not restricted to linguistic (phonological) stimuli, supporting a general auditory processing impairment in phonologic dyslexia.

Objective: To compare the 'F(fusion)-complex' with the Mismatch negativity (MMN), both components associated with automatic detection of changes in the acoustic stimulus flow., Methods: Ten right-handed adult native Hebrew speakers discriminated vowel-consonant-vowel (V-C-V) sequences /ada/ (deviant) and /aga/ (standard) in an active auditory 'Oddball' task, and the brain potentials associated with performance of the task were recorded from 21 electrodes. Stimuli were generated by fusing the acoustic elements of the V-C-V sequences as follows: base was always presented in front of the subject, and formant transitions were presented to the front, left or right in a virtual reality room. An illusion of a lateralized echo (duplex sensation) accompanied base fusion with the lateralized formant locations. Source current density estimates were derived for the net response to the fusion of the speech elements (F-complex) and for the MMN, using low-resolution electromagnetic tomography (LORETA). Statistical non-parametric mapping was used to estimate the current density differences between the brain sources of the F-complex and the MMN., Results: Occipito-parietal regions and prefrontal regions were associated with the F-complex in all formant locations, whereas the vicinity of the supratemporal plane was bilaterally associated with the MMN, but only in case of front-fusion (no duplex effect)., Conclusions: MMN is sensitive to the novelty of the auditory object in relation to other stimuli in a sequence, whereas the F-complex is sensitive to the acoustic features of the auditory object and reflects a process of matching them with target categories., Significance: The F-complex and MMN reflect different aspects of auditory processing in a stimulus-rich and changing environment: content analysis of the stimulus and novelty detection, respectively.

Children with dyslexia have difficulties with phonological processing. It is assumed that deficits in auditory temporal processing underlie the phonological difficulties of dyslectic subjects (i.e. the processing of rapid acoustic changes that occur in speech). In this study we assessed behavioral and electrophysiological evoked brain responses of dyslectic and skilled reading children while performing a set of hierarchically structured auditory tasks. Stimuli consisted of auditory natural unmodified speech that was controlled for the parameter of changing rate of main acoustic cues: vowels (slowly changing speech cues: /i/ versus /u/) and consonant-vowel (CV) syllables (rapidly changing speech cues: /da/ versus /ga/). Brain auditory processing differed significantly between groups: reaction time of dyslectic readers was prolonged in identifying speech stimuli and increased with increased phonological demand. Latencies of auditory evoked responses (auditory event related potentials [AERPs]) recorded during syllable identification of the dyslectic group were prolonged relative to those of skilled readers. Moreover, N1 amplitudes during vowel processing were larger for the dyslectic children and P3 amplitudes during CV processing were smaller for the dyslectic children. From the results of this study it is evident that the latency and amplitude of AERPs are sensitive measures of the complexity of phonological processing in skilled and dyslectic readers. These results may be signs of deficient auditory processing of natural speech under normal listening conditions as a contributing factor to reading difficulties in dyslexia. Detecting a dysfunction in the central auditory processing pathway might lead to early detection of children who may benefit from phonetic-acoustic training methods.

Objective: To study effects of forward masking and rapid stimulation on human monaurally- and binaurally-evoked brainstem potentials and suggest their relation to synaptic fatigue and recovery and to neuronal action potential refractoriness., Methods: Auditory brainstem evoked potentials (ABEPs) were recorded from 12 normally- and symmetrically hearing adults, in response to each click (50 dB nHL, condensation and rarefaction) in a train of nine, with an inter-click interval of 11 ms, that followed a white noise burst of 100 ms duration (50 dB nHL). Sequences of white noise and click train were repeated at a rate of 2.89 s(-1). The interval between noise and first click in the train was 2, 11, 22, 44, 66 or 88 ms in different runs. ABEPs were averaged (8000 repetitions) using a dwell time of 25 micros/address/channel. The binaural interaction components (BICs) of ABEPs were derived and the single, centrally located equivalent dipoles of ABEP waves I and V and of the BIC major wave were estimated., Results: The latencies of dipoles I and V of ABEP, their inter-dipole interval and the dipole magnitude of component V were significantly affected by the interval between noise and clicks and by the serial position of the click in the train. The latency and dipole magnitude of the major BIC component were significantly affected by the interval between noise and clicks. Interval from noise and the click's serial position in the train interacted to affect dipole V latency, dipole V magnitude, BIC latencies and the V-I inter-dipole latency difference. Most of the effects were fully apparent by the first few clicks in the train, and the trend (increase or decrease) was affected by the interval between noise and clicks., Conclusions: The changes in latency and magnitude of ABEP and BIC components with advancing position in the click train and the interactions of click position in the train with the intervals from noise indicate an interaction of fatigue and recovery, compatible with synaptic depletion and replenishing, respectively. With the 2 ms interval between noise and the first click in the train, neuronal action potential refractoriness may also be involved.

Objective: The purpose of this study was to define early brain activity associated with fusion of speech elements to form an auditory object in the middle-latency range preceding the F-Complex., Methods: Stimuli were binaural formant transition and base, that were presented separately or fused to form the vowel-consonant-vowel sequence /ada/. Eleven right-handed, adult, native Hebrew speakers listened to 2/s presentations, and the brain potentials from C(z) during the 250 msec following transition onset (in the responses to transition and to the fused word) or following the time it would have been presented (in the response to base alone) were recorded. The net-fusion response was extracted by subtracting the sum of potentials to the base and the formant transition from the potentials to the fused sound., Results: Auditory middle-latency components, comprising of 9 peaks and troughs were recorded in response to the base, to the formant transition and to the fused /ada/. In general, the responses to the fused object were significantly smaller in peak amplitude and in total activity (area under the curve) resulting in the difference waveform of the net-fusion response that also included 9 peaks, but with opposite polarities., Conclusions: The early middle-latency components to fusion indicate that the fusion of speech elements to a word involves inhibition, occlusion or both. The results are in line with the uniqueness of speech perception and the early role of the auditory cortex in speech analysis.

Category induction involves abstraction of features common to two or more stimuli. We predicted that category induction affects processing of each stimulus, before completion of perceptual analysis. Event-related potentials (ERPs) were recorded from ten 11-13-year olds while they were performing visual category-induction tasks. Subjects viewed a series of two geometric shapes belonging to the same perceptual category (size, color, or shape), defined by one or two shared features, and decided if a probe stimulus shared membership in that category. Large frontal N120, frontal-central N300 and smallest P450 were elicited by the first stimulus; number of shared features affected P150, N170, and P450 amplitudes to the second stimulus. Principal Component Analysis (PCA) indicated networks of frontal, parietal and occipital activity, different to each stimulus. Results suggest that in young adolescents category induction affects early stages of stimulus processing. Processing is based on selective analysis of stimuli for shared features, not exhaustive examination of all features of all stimuli.

Purpose: Auditory processing of increasing acoustic and linguistic complexity was assessed in children with idiopathic generalized epilepsy (IGE) by using auditory event-related potentials (AERPs) as well as reaction time and performance accuracy., Methods: Twenty-four children with IGE [12 with generalized tonic-clonic seizures (GTCSs), and 12 with absence seizures (ASs)] with average intelligence and age-appropriate scholastic skills, uniformly medicated with valproic acid (VPA), and 20 healthy controls, performed oddball discrimination tasks that consisted of the following stimuli: (a) pure tones; (b) nonmeaningful monosyllables that differed by their phonetic features (i.e., phonetic stimuli); and (c) meaningful monosyllabic words from two semantic categories (i.e., semantic stimuli)., Results: AERPs elicited by nonlinguistic stimuli were similar in healthy and epilepsy children, whereas those elicited by linguistic stimuli (i.e., phonetic and semantic) differed significantly in latency, amplitude, and scalp distribution. In children with GTCSs, phonetic and semantic processing were characterized by slower processing time, manifested by prolonged N2 and P3 latencies during phonetic processing, and prolongation of all AERPs latencies during semantic processing. In children with ASs, phonetic and semantic processing were characterized by increased allocation of attentional resources, manifested by enhanced N2 amplitudes. Semantic processing also was characterized by prolonged P3 latency. In both patient groups, processing of linguistic stimuli resulted in different patterns of brain-activity lateralization compared with that in healthy controls. Reaction time and performance accuracy did not differ among the study groups., Conclusions: AERPs exposed linguistic-processing deficits related to seizure type in children with IGE. Neurologic follow-up should therefore include evaluation of linguistic functions, and remedial intervention should be provided, accordingly.

Objective: Auditory event-related brain potentials (ERPs) were recorded during a lexical decision task in response to linguistic and non-linguistic stimuli, to assess the detailed time course of language processing in general, and hemispheric dominance in particular., Methods: Young adults (n=17) were presented with pairs of auditory stimuli consisting of words, pseudowords and words played backwards in a lexical decision task. ERPs were recorded from 21 scalp electrodes. Current densities were calculated using low-resolution electromagnetic tomography (LORETA). Statistic non-parametric maps of activity were derived from the calculated current densities and the number of active brain voxels in the left and right hemispheres was compared throughout the processing of each stimulus., Results: Our results show that hemispheric dominance is highly time dependent, alternating between the right and left hemispheres at different times, and that the right hemisphere's role in language processing follows a different time course for first and second language. The time course of hemispheric dominance for non-linguistic stimuli was highly variable., Conclusions: The time course of hemispheric dominance is dynamic, alternating between left and right homologous regions, with different time courses for different stimulus classes.

We recorded event related brain potentials to assess stages of linguistic processing of first (L1) and second (L2) language and of pseudowords when subjects were engaged in a different task and did not attend to the words. Young adults (n = 15) were presented with pairs of auditory stimuli consisting of words and pseudowords in L1 and L2 with different voice onset times (VOT), which served as distracters in a short-term memory task. ERPs were recorded from 11 scalp electrodes. The ERP peak amplitudes and latencies were subjected to analysis of variance for the effects of language, meaning and scalp location as well as priming of the second word in the pair by the preceding word. Behavioral results showed that attention was drawn to the primary task and away from the words; yet significant, including semantic, processing was evident in the ERPs to the words, with significant effects of language, meaning and priming. Even with barely any awareness of the stimuli, the brain processes words including distinguishing between L1 and L2 and relating to the stimuli's context.

This study was designed to follow the time course of different levels of linguistic processing using auditory event-related potentials (AERPs). A hierarchical set of acoustically controlled stimuli was used to elicit AERPs in 20 normal children who performed discrimination tasks involving pure tones, phonetic 'easy' and 'difficult' stimuli and semantic stimuli. Results show that (1) AERP latencies were similar for phonetic 'easy' and 'difficult' stimuli, (2) prolonged P(2), N(2) and P(3) latencies characterized semantic processing compared to phonetic processing, (3) a late negativity was elicited during semantic processing only, (4) P(3) amplitudes were larger over the left compared to right scalp during linguistic processing (phonetic and semantic) but were similar during nonlinguistic processing (pure tones) and (5) reaction time was found to be longest for semantic processing whereas performance accuracy was found to be an insensitive measure. These results provide insight into brain processes underlying the perception of speech. Furthermore, they support a dual model of speech perception that includes parallel and serial processing., (Copyright 2002 S. Karger AG, Basel)

The purpose of the studies summarized in this report was to determine the time course of auditory cortex involvement in speech and language processing in the context of auditory object formation. Forty-one subjects took part in the three studies summarized in this report. In all three studies, subjects performed a choice-reaction task that required their pressing an appropriate button in response to auditory stimuli (speech/non-speech, good/worse fused phonemes, first/second language words) presented through earphones. Event-related potentials (ERPs) were recorded during performance of the task from 21 scalp electrodes, in addition to peri-ocular electrodes for monitoring eye movements. Current densities within the gray matter of the brain were estimated using the LORETA (low resolution electromagnetic tomography) method. In general, except for some periods, processing phonetic and linguistic information was associated with elevated activity in the left auditory cortex. Peaks in auditory cortex activation corresponded in time to scalp recorded peaks in the latencies of P1 and up to as late as P3. The adjacent posterior temporal areas showed a similar temporal pattern of activation, but tended to be less lateralized to the left, or even biased toward right hemisphere predominance, depending on the stimulus, particularly in the later time frames. The results indicate that the auditory cortex is engaged in auditory processing from its early stages and as long as a few hundreds of msec, even after cessation of the stimulus, defining sounds as distinct auditory objects and differentiating speech from non-speech material, relying on acoustic cues. Hemispheric dominance fluctuates to include activity in the 'non-dominant' hemisphere depending on stimulus type and stage of processing.