Suha Yagcioglu

Differences between the N1 waves of the responses to interaural time and intensity disparities: scalp topography and dipole sources☆

OBJECTIVES Being the two complementary cues to directional hearing, interaural time and intensity disparities (ITD and IID, respectively), are known to be separately encoded in the brain stem. We address the question as to whether their codes are collapsed into a single lateralization code subcortically or they reach the cortex via separate channels and are processed there in different areas. METHODS Two continuous trains of 100/s clicks were dichotically presented. At 2 s intervals either an interaural time delay of 1ms or an interaural level difference of 20 dB (HL) was introduced for 50 ms, shifting the intracranial sound image laterally for this brief period of time. Long-latency responses to these directional stimuli, which had been tested to evoke no potentials under monotic or diotic conditions, as well as to sound pips of 50 ms duration were recorded from 124 scalp electrodes. Scalp potential and current density maps at N1 latency were obtained from thirteen normal subjects. A 4-sphere head model with bilaterally symmetrical dipoles was used for source analysis and a simplex algorithm preceded by a genetic algorithm was employed for solving the inverse problem. RESULTS Inter- and intra-subject comparisons showed that the N1 responses evoked by IID and ITD as well as by sound pip stimuli had significantly different scalp topographies and interhemispheric dominance patterns. Significant location and orientation differences between their estimated dipole sources were also noted. CONCLUSIONS We conclude that interaural time and intensity disparities (thus the lateral shifts of a sound image caused by these two cues) are processed in different ways and/or in different areas in auditory cortex.

Interaural delay-dependent changes in the binaural difference potential in cat auditory brainstem response: implications about the origin of the binaural interaction component

Auditory brainstem responses (ABRs) evoked by dichotic clicks with 12 different interaural delays (ITDs) between 0 and 1500 microsecond(s) were recorded from the vertices of 10 cats under ketamine anesthesia. The so-called binaural difference potential (BDP), considered to be an indicator of binaural interaction (BI), was computed by subtracting the sum of the two monaural responses from the binaural one. The earliest and most prominent component of BDP was a negative deflection (DN1) at a latency between 4 and 4.8 ms. Like all the other components of BDP, DNI was also due to binaural reduction rather than enhancement of the corresponding ABR wave, P4 in this case. Furthermore, the way its latency increased as a function of ITD was also not compatible with what would be predicted by the delay-line coincidence detector models based on the excitatory-excitatory units in the medial superior olive (MSO). We therefore proposed an alternative hypothesis for the origin of this BI component based on the inhibitory-excitatory (IE) units in the lateral superior olive (LSO). The computational model designed closely simulated the ITD-dependent attenuation and latency shifts observed in DN1. It was therefore concluded that the origin of this BI component in the cats vertex-ABR could be the lateral lemniscal output of the LSO, although the delay lines which have been shown to exist also in the mammalian brain may play an important role in encoding ITDs.

Neuropsychological performance and auditory event related potentials in schizophrenia patients and their siblings: A family study

BACKGROUND Various neuropsychological domains, and P300 auditory event-related potentials (ERP) and mismatch negativity (MMN) exhibit abnormalities in schizophrenia patients and their first-degree relatives. The aims of this study were to compare cognitive and P300/MMN measurements in schizophrenia patients, their siblings, and controls, and to identify the degree of familial influence on each measure. METHODS Thirty patients diagnosed with schizophrenia according to DSM-IV, 20 unaffected siblings and 25 healthy controls were able to complete all neuropsyhological and neurophysiological assessments. All participants were administered SCID-I and the patients were also evaluated regarding symptom severity and functioning. Neuropsychological battery testing results and P300/MMN measurements were obtained for all the participants. RESULTS Both schizophrenia patients and their siblings had lower working memory, as measured by the Auditory Consonant Trigram Test (ACT), and lower MMN amplitude scores than the controls. In addition, the patients had lower attention, verbal memory, executive function, visuomotor speed, and figural memory scores than both the siblings and controls, and lower verbal fluency scores than controls. MMN and P300 amplitudes were lower and P300 latency longer in the schizophrenia patients, as compared to controls. P300 latency was also longer in the schizophrenia patients as compared to siblings and, MMN amplitudes were significantly lower in the siblings compared to controls. Working memory performance measured by ACT significantly predicted inclusion in both the patient and sibling groups and showed significant familial influence. MMN amplitude significantly predicted inclusion only to the patient group and did not show significant familial influence. CONCLUSION The schizophrenia patients exhibited impairment in various cognitive domains and P300/MMN measurements, versus impairment only in working memory and MMN amplitude in their siblings. Working memory seems to have a relatively strong familial influence among all the neuropsychological and neurophysiological parameters evaluated.

Lamotrigine augmentation in patients with schizophrenia who show partial response to clozapine treatment.

BACKGROUND Several placebo controlled studies investigating lamotrigine augmentation of clozapine in schizophrenia patients with partial response have shown varying results. The aim of this study was to further investigate the efficacy and safety of this augmentation strategy, and its effect on the glutamatergic system through utilizing mismatch negativity (MMN) component of auditory event related potentials. METHODS The study was designed to evaluate the efficacy and safety of lamotrigine augmentation of clozapine in a 12-week, double-blind, placebo-controlled, prospective, randomized design. Thirty-four patients diagnosed according to DSM-IV schizophrenia criteria and with partial response to clozapine were included. Patients were randomized to 25mg/day of lamotrigine or placebo, gradually increasing up to 200mg/day on the 6th week. The change in psychopathology was assessed with Positive and Negative Syndrome (PANSS), Calgary Depression (CDS) and Clinical Global Impression-Severity (CGI-S) scales. A neuropsychological test battery was administered and MMN measurements were also obtained at baseline and endpoint. Safety evaluation included physical examination, UKU Side Effect Rating Scale (UKU) assessment and serum drug level measurements. RESULTS No significant differences were found between the two treatment groups in PANSS Positive and General Psychopathology, CDS, neurocognitive test and UKU scores, as well as MMN measurements. PANSS Total, Negative and CGI-S scores showed significant improvement compared to lamotrigine in the placebo group. CONCLUSION This study did not show any benefit of augmentation of clozapine with lamotrigine in schizophrenia patients with partial response. The need for further investigation of other augmentation strategies of clozapine in partially responsive schizophrenia patients is evident.

Origin of the binaural interaction component in wave P4 of the short-latency auditory evoked potentials in the cat: evaluation of serial depth recordings from the brainstem

There is no general agreement on the origin of the binaural interaction (BI) component in auditory brainstem responses (ABRs). To study this issue the ABRs to monaural and binaural clicks with various interaural time differences (ITDs) were simultaneously recorded from the vertex and from a recording electrode aiming at the superior olive (SO) in cats. Electrode path was along the fibers of the lateral lemniscus (LL). Binaural difference potentials (BDPs), which were computed by subtracting the sum of the two monaural responses from the binaural response, were obtained at systematic depths and across a range of ITD values. It was observed that only a specific BDP deflection recorded at the level at which lemniscal fibers terminate in the nuclei of LL coincided in time with the most prominent BDP in the cats vertex-recorded ABRs, the BDP in their wave P4. As ITD was increased, the latency shifts and amplitude decrements of the scalp-recorded far-field BDP wave exactly followed those recorded at this lemniscal near-field BDP locus. The data support our hypothesis that the BI component in wave P4 results from a binaural reduction in dischargings of axons ascending in the LL, with this reduction due to contralateral inhibition of the discharge activity of the inhibitory-excitatory units in the lateral nucleus of the SO. Furthermore, at the level of the SO, the BDP in the responses to contra-leading binaural clicks always had larger magnitudes than those evoked by ipsi-leading ones. This bilateral asymmetry is consistent with the view that the BDP in scalp-recorded ABRs is related to the function of sound lateralization.

Interaural delay-dependent changes in the binaural interaction component of the guinea pig brainstem responses ☆

Auditory brainstem responses to monaural and binaural clicks with 23 different interaural time differences (ITDs) were recorded from ten guinea pigs without anesthesia. Binaural interaction component was obtained by subtracting the sum of the appropriately time-shifted left and right monaural responses from the binaural one. With increasing ITD, the most prominent peak of the binaural difference potential so obtained shifted to longer latencies and its amplitude gradually decreased. The way these changes depended on binaural delay was basically similar to that previously observed in a cat study [P. Ungan, S. Yagcioglu, B. Ozmen. Interaural delay-dependent changes in the binaural difference potential in cat auditory brainstem response: implications about the origin of the binaural interaction component. Hear. Res. 106 (1997) 66-82]. The data were successfully simulated by the model suggested in that report. We therefore concluded that the same model, which was based on the difference between the mean onset latencies of the ipsilateral excitation and contralateral inhibition in a typical neuron in the lateral superior olive, their standard deviations, and the duration of the contralateral inhibition, should also be valid for the binaural interaction in the guinea pig brainstem. The results, which were discussed in connection with sound lateralization models, supported a model based on population coding, where the lateral position of a sound source is coded by the ratio of the discharge intensity in the left and right lateral superior olives, rather than the models based on coincidence detection.

Refractoriness, habituation, and mismatch effects in the auditory event-related potential to alternating stimuli.

Amplitude enhancement in the N1 component of auditory event-related potentials (ERPs) to alternately presented sounds has been referred as a typical example for the effect of release from neural refractoriness. We tested this hypothesis to see whether some other effects also contribute to this phenomenon. Two tones of different frequencies were presented singly or in pairs, and ERPs were recorded using monotonous (mnt) and alternating (alt) sequences of these stimuli. Comparison of the ‘alt–mnt’ difference waveforms recorded with single and paired stimuli supported the refractoriness hypothesis. A mismatch negativity-like wave, however, was also observed, questioning the constraint of ‘at least two consecutive standards before deviant’ presumed in most mismatch negativity studies. This paradigm made it possible to delineate the ERP components related to refractoriness and mismatch detection processes.

Electrophysiological assessment of the effects of obstructive sleep apnea on cognition.

We used electrophysiological measures to investigate the effects of obstructive sleep apnea on attention, learning, and memory. Thirty subjects (OSA group, n = 15, control group n = 15) participated in n-back tests, accompanied by P300 recordings, to investigate working memory and attention. The mirror-drawing test was used to study procedural memory, and the trail-making test (TMT) was used to evaluate divided attention and executive function. No significant group difference in reaction time was found in the 0-back and 1-back tests. In the 2-back test, reaction times of patients were longer than those of the control group. No P300 wave was obtained in the OSA group in any (0-, 1-, or 2-back) n-back test. In contrast, in the control group, significant P300 waves were recorded except for the 2-back test. The mirror-drawing scores were unaffected by sleep apnea. There was no difference between groups in the TMT-A test on any of the trials. Although no group difference was found in the first or second trials of the TMT-B test, OSA patients were less successful in learning on the third trial. According to our study results, OSA affects attention and executive function adversely however, we could not detect a significant effect on working or procedural memory.

Event-related potentials to changes of rhythmic unit: differences between musicians and nonmusicians.

We investigated whether the expected differences between musicians and nonmusicians in their ability to detect a rhythm change were reflected in their event-related potentials (ERPs) and, if reflected, how these ERP differences associated with behavioral indices. Stimuli were three consecutive and equally spaced drum beats followed by a rest period to form a rhythmic unit (RU). By using three different inter-beat periods, three RUs were produced. Combinations of these RUs served as the “target/standard” pairs of an oddball sequence. In four different experiments, we tried two RU-change types each with two levels of detection difficulty. ERPs were recorded from the F3, Fz, F4, Cz and Pz scalp sites of 12 musicians and 12 nonmusicians. RT, hit and false-alarm rates were also measured. The data have shown with high statistical confidence that, associated with the musicians’ better detection performance and shorter RTs, their ERP P3 to rhythm changes peaked significantly earlier and was significantly larger compared to nonmusicians. Intergroup ERP differences allowed above 90% correct classification. This study has also showed that not only violations of relatively complex musical regularities, but very simple rhythmic unit alterations could lead to significant P3 differences between musicians and nonmusicians. The high accuracy of the musician/nonmusician classification based only on their P3 data strongly supported the hypothesis that sensory and/or cognitive advantage of musicians in detecting rhythm changes does reflect in their P3.

Lidocaine diminishes arrhythmia by Leiurus quinquestriatus quinquestriatus venom in rats

The venom from the scorpion Leiurus quinquestriatus quinquestriatus has previously been shown to alter the excitability of the neural and skeletal muscle preparations. The present study was undertaken to explore the effects of the venom in cardiac potential signals at the animal, tissue and the cell level in rats hearts.