500-ms Interstimulus Intervals Research Articles

Large-Scale Networks for Auditory Sensory Gating in the Awake Mouse.

The amplitude of the brain response to a repeated auditory stimulus is diminished as compared to the response to the first tone (T1) for interstimulus intervals (ISI) lasting up to hundreds of milliseconds. This adaptation process, called auditory sensory gating (ASG), is altered in various psychiatric diseases including schizophrenia and is classically studied by focusing on early evoked cortical responses to the second tone (T2) using 500-ms ISI. However, mechanisms underlying ASG are still not well-understood. We investigated ASG in awake mice from the brainstem to cortex at variable ISIs (125–2000 ms) using high-density EEG and intracerebral recordings. While ASG decreases at longer ISIs, it is still present at durations (500–2000 ms) far beyond the time during which brain responses to T1 could still be detected. T1 induces a sequence of specific stable scalp EEG topographies that correspond to the successive activation of distinct neural networks lasting about 350 ms. These brain states remain unaltered if T2 is presented during this period, although T2 is processed by the brain, suggesting that ongoing networks of brain activity are active for longer than early evoked-potentials and are not overwritten by an upcoming new stimulus. Intracerebral recordings demonstrate that ASG is already present at the level of ventral cochlear nucleus (vCN) and inferior colliculus and is amplified across the hierarchy in bottom-up direction. This study uncovers the extended stability of sensory-evoked brain states and long duration of ASG, and sheds light on generators of ASG and possible interactions between bottom-up and top-down mechanisms.

Auditory sensory gating to the human voice: A preliminary MEG study

The ability of the brain to suppress incoming irrelevant sensory input is termed ‘sensory gating,' and auditory sensory gating is often indexed by the auditory evoked response. We recorded the auditory evoked magnetic fields to the human voice, using the conditioning–testing paradigm, to investigate whether or not healthy subjects show less activation to the second voice stimulus. Seventeen healthy adults (mean age 27.9 ± 4.8 years, 9 males and 8 females) participated in the experiment. The auditory stimuli were presented monaurally as a series of 120 paired voices, with 500-ms interstimulus intervals and 6-s interpaired stimulus intervals. The P50m and the N100m responses were investigated, and dipole source localization was performed. Root mean squares of both P50m and N100m were significantly suppressed to the second stimulus bilaterally, and the suppression was more significant in N100m. The N100m was located significantly more laterally than the P50m for both hemispheres. These results therefore demonstrate the presence of sensory gating for auditory inputs of the human voice in the primary auditory cortex and the auditory association area.

Word Cognate Status and Concreteness: ERPs in L1 and L2 processing

Event Abstract Back to Event Word Cognate Status and Concreteness: ERPs in L1 and L2 processing Ivo Popivanov1*, A. Janyan1 and E. Andonova1, 2 1 New Bulgarian University, Bulgaria 2 Bremen University, Germany To address the issue of bilingual language representation and processing we crossed a semantic variable (concreteness) and the cognate status of words in a translation verification task. Cognates are words that have a similar form and meaning in both languages (L1 & L2) while non-cognates in a translation task have similarity in meaning but not in word form. The general finding is that cognates are recognized and produced faster than non-cognates (e.g., Kroll & Stewart, 1994) which are usually attributed to a common set of form-based representations across the two languages. Models of bilingual language processing disagree on the issue whether cognate processing is affected by overlapping representations at the lexical level only or the semantics beyond (Kroll & De Groot, 1997). We test the models’ predictions and examine the extent to which semantics (more specifically, concreteness, i.e., concrete vs. abstract words) is involved in cognate vs. non-cognate processing. 11 young Bulgarian-English bilinguals performed a single word translation verification task from L2 (English) into L1 (Bulgarian). The words were presented for 300 ms with a 500-ms interstimulus interval and with an intertrial interval that varied between 1700 and 2200 ms. We used a go/no go task (to press a button if a non-equivalent translation is detected and do not press a button if the second word is a translation equivalent). Grand average ERPs were analysed during both L2 and L1 processing in two time windows on mean amplitude. A repeated-measure ANOVA showed that during L2 word processing the semantics of non-cognates was activated starting from 140 ms after stimulus onset while for cognates it was only activated later, starting at word offset. In addition, the magnitude of the cognate effect was larger during the second time interval, i.e., at later stages of processing. Furthermore, the analyses suggested that during the phase of translation recognition (L1 word processing) cognate processing did not involve semantics in either time window while non-cognate processing did activate it starting from 200 ms after word onset till the end of the second window (600 ms). This study shows for the first time that cognate processing in L2 activates semantics very early which is consistent with studies on monolinguals (see Pulvermüller, 2007). Overall, the results offer support to word processing in the bilingual’s two languages being semantically mediated and affected by the cognate status of words, and it thus contributes to our understanding of language representation in bilinguals. Findings are discussed in terms of the models of bilingual language representaion (Kroll & De Groot, 1997).

Noradrenergic antagonism of the P13 and N40 components of the rat auditory evoked potential

Two rat auditory evoked potential (AEP) components P13 and N40 are suggested as analogues to the human P50, which has abnormal suppression properties in schizophrenia. However, P50 likely reflects neural activity from several different brain areas. Studies examining each of these components in the rat model have proposed circuitry that involves alpha2 norepinephrine (NE) receptors, and different disruption effects are predicted depending on whether effects are presynaptic or postsynaptic. The aim of this paper is to test differential effects of NE antagonism on disruption of normal P13 and N40 expression. AEPs were recorded simultaneously in alert, freely moving rats using the alpha2 antagonist yohimbine. Amplitudes of P13 and N40 elicited by 500-ms interstimulus interval click pairs were measured after administration of a placebo and three doses of the yohimbine. A high dose of yohimbine yielded smaller P13 amplitudes to both clicks, consistent with presynaptic action. However, a moderate yohimbine dose yielded increased P13 amplitudes to both clicks. For N40, a moderate dose of yohimbine yielded increased amplitudes to the second stimulus, and a high dose restored normal suppression, which is consistent with previously reported findings. This study demonstrated that noradrenergic activity differentially affects P13 and N40 components. As P13 and N40 are each models of human P50, these findings highlight the complex circuitry that likely underlies P50. An appreciation for these complexities is critical for understanding the mechanisms of the P50 suppression deficit in schizophrenia, which may be influenced by both trait and state factors.

Prepulse inhibition and P50 suppression: Commonalities and dissociations

Patients with schizophrenia exhibit reduced levels of both prepulse inhibition of the startle reflex (PPI) and condition-test suppression of the P50 event-related potential. This study investigated the extent to which PPI and P50 suppression, which exhibit similar parametric sensitivities, are intrinsically auditory phenomena or can be induced cross-modally, and reflect common or distinct neural mechanisms of inhibition. PPI, N100, and P50 were assessed in 20 healthy male volunteers, using auditory test probes and both visual and auditory lead stimuli, separated by 100- or 500-ms interstimulus intervals (ISIs). PPI was found in the auditory-lead condition across the complete group, and with visual-lead stimuli in approximately half of the subjects. Intra-modal auditory PPI was significantly higher with the 100-ms ISI than with the 500-ms ISI. P50 suppression was found only with the 500-ms ISI, with no difference between the auditory and visual conditions. Source analyses revealed that suppression was associated with frontal cortical activity. N100 suppression was found only in the auditory condition, with no difference between 100- and 500-ms ISIs. Although both phenomena are considered to provide operational measures of gating, PPI and P50 suppression are differentially sensitive to ISI and therefore reflect partly different neural mechanisms. They are not intrinsically auditory phenomena, and both appear to involve frontal cortical activity. In contrast, N100 suppression is most likely based on refractory mechanisms intrinsic to the auditory system.

Cross‐modal generality of the gating deficit

Auditory P50/M50 paired-click studies have established an association between schizophrenia and impaired sensory gating in the auditory modality. However, the presumed cross-modal generality of the gating deficit has received little study. The present study examined gating in area 3b of primary somatosensory cortex to evaluate patients' somatosensory gating at this first stage of cortical processing. One hundred twenty-two channels of magnetoencephalography (MEG) data were collected from 27 subjects with chronic schizophrenia and 21 controls during a somatosensory paired-pulse paradigm with a 75- or 500-ms interstimulus interval. M20 somatosensory responses were localized using magnetic source imaging, and a gating ratio was calculated. In a subset of these subjects, MEG was also done for the standard auditory paradigm to assess M50 gating. Patients showed abnormal auditory M50 gating but normal somatosensory M20 gating. Results argue against a cross-modal gating deficit in primary somatosensory cortex.

Levetiracetam has no significant γ-aminobutyric acid-related effect on paired-pulse interaction in the dentate gyrus of rats

γ-Aminobutyric acid (GABA)ergic mechanisms of the novel antiepileptic drug, levetiracetam ( Keppra®), have been both favored and rejected. Since paired-pulse interaction is accepted in functionally assessing GABAergic mechanisms, we investigated whether levetiracetam affects the paired-pulse inhibition/facilitation of the field potentials, evoked in the dentate gyrus of urethane-anesthesized rats. This model revealed a strong paired-pulse inhibition at 20-ms interstimulus interval, a noteworthy paired-pulse facilitation at 80-ms interstimulus interval, and a moderate paired-pulse inhibition at 500-ms interstimulus interval. Bicuculline (3 mg/kg/h, i.v.) and baclofen (10 mg/kg, i.v.) markedly depressed paired-pulse inhibition at 20-ms interstimulus interval, while clonazepam (1 mg/kg, i.p.), diazepam (10 mg/kg, i.v.), and phenobarbital (40 mg/kg, i.v.) enhanced it. Bicuculline also depressed paired-pulse inhibition at 500-ms interstimulus interval. Bicuculline, baclofen, and diazepam reduced paired-pulse facilitation at 80-ms interstimulus interval. Distinct from these GABA A receptor- and GABA B receptor-related drugs, levetiracetam (17 and 540 mg/kg, i.v.) had no significant effect on either paired-pulse interaction in this model, a result not favoring any major role of GABAergic mechanisms in its antiseizure action.

Decreased habituation of midlatency auditory evoked responses in Parkinson's disease.

The P1 midlatency auditory evoked potential was studied in patients with Parkinson's disease and compared to that in age-matched controls. Habituation of the potential was determined by using a two-click stimulus paradigm in which the stimuli were presented at 250-, 500-, and 1,000-ms interstimulus intervals. Results showed that habituation of the P1 potential had a statistically significant decrease at the 250-ms and 500-ms interstimulus intervals in patients with Parkinson's disease compared to normal controls. The degree of decreased habituation was found to increase with severity of the disease such that stage 5 patients showed greater decreases in habituation compared to stage 4, as did stage 4 compared to stage 3. These findings may be explained by the presence of a dysregulation of sensory processing, possibly by elements of the reticular activating system, including the pedunculopontine nucleus, in Parkinson's disease.

Identification and change/no-change discrimination of [i] stimuli: Further tests of the ‘‘magnet’’ effect

In original work Kuhl [Percept. Psychophys. 50, 93–107 (1991)] used a stimulus that was 120 mels away from the prototype (P) stimulus for demonstration of the ‘‘magnet’’ effect. Listeners in the current study who phonetically transcribed P and nonprototype (NP) [i] stimuli showed that 92% of responses for the 120-mel P token were not [i]. Further, another group of listeners rated the 64 stimuli as either the [i] in ‘‘peep’’ or ‘‘not [i].’’ Results showed that only 20% of responses rated the 120-mel token as [i] suggesting that this token along the −1 diagonal was not considreed an [i] member. Thus three other groups of listeners participated in ‘‘change/no-change’’ discrimination testing with 500-ms interstimulus intervals for stimuli along the −1 diagonal common to the P and NP distributions. Each group had a different fixed standard in each four-item trial: the Kuhl P token, the 120-mel token, and an 85-mel token. Results will be discussed according to the effects of different standards on discrimination sensitivity and prototype theories in phonetic perception.