Comparison of LFP-Based and Spike-Based Spectro-Temporal Receptive Fields and Cross-Correlation in Cat Primary Auditory Cortex

Multi-electrode array recordings of spike and local field potential (LFP) activity were made from primary auditory cortex of 12 normal hearing, ketamine-anesthetized cats. We evaluated 259 spectro-temporal receptive fields (STRFs) and 492 frequency-tuning curves (FTCs) based on LFPs and spikes simultaneously recorded on the same electrode. We compared their characteristic frequency (CF) gradients and their cross-correlation distances. The CF gradient for spike-based FTCs was about twice that for 2–40 Hz-filtered LFP-based FTCs, indicating greatly reduced frequency selectivity for LFPs. We also present comparisons for LFPs band-pass filtered between 4–8 Hz, 8–16 Hz and 16–40 Hz, with spike-based STRFs, on the basis of their marginal frequency distributions. We find on average a significantly larger correlation between the spike based marginal frequency distributions and those based on the 16–40 Hz filtered LFP, compared to those based on the 4–8 Hz, 8–16 Hz and 2–40 Hz filtered LFP. This suggests greater frequency specificity for the 16–40 Hz LFPs compared to those of lower frequency content. For spontaneous LFP and spike activity we evaluated 1373 pair correlations for pairs with >200 spikes in 900 s per electrode. Peak correlation-coefficient space constants were similar for the 2–40 Hz filtered LFP (5.5 mm) and the 16–40 Hz LFP (7.4 mm), whereas for spike-pair correlations it was about half that, at 3.2 mm. Comparing spike-pairs with 2–40 Hz (and 16–40 Hz) LFP-pair correlations showed that about 16% (9%) of the variance in the spike-pair correlations could be explained from LFP-pair correlations recorded on the same electrodes within the same electrode array. This larger correlation distance combined with the reduced CF gradient and much broader frequency selectivity suggests that LFPs are not a substitute for spike activity in primary auditory cortex

CiprofloxacinDexamethasone ototoxicity in an animal and human model

Introduction. Ototoxicity refers to medication-caused auditory and/or vestibular system dysfunction resulting in hearing loss or dysequilibrium. The potential damage that antibiotics eardrops can produce when placed directly into the middle ear in some cases is still unknown.Objectives. To determine the safety of use of the new ciprofloxacin/dexamethasone otic drops in patients without an intact tympanic membrane.Materials and methods. Ciprodex/dexamethasone eardrops were tested in an animal and human model. The animal part was performed in 13 adult chinchillas; Auditory Brainstem Response (ABR) was used. For the human part, twenty subjects were enrolled in the study; Distortion Products Otoacoustic Emissions (DPOAE) testing was used.Results. Animal Part: after the tube insertion ABR threshold mean value was 19.6+/-13.3 dB for all the animals. On the last evaluation (day 60), the mean threshold was 19+/-13 dB for the experimental ears, and 13.7+/-12.2 dB for the control ears, this overall analysis showed no significant effect (p-value = 0.661). Human Part: the mean thresholds for the pre-treatment test were 4.87+/-6,34 dB for the DP value and -0.87+/-7.93 dB for the Ns value. In the post-treatment evaluation the mean thresholds were 3.48+/-4.40 dB for the DP value and -8.02+/-7.57 dB for the Ns value.Conclusions. The use of CiprodexTM eardrops seems to be safe when instilled in ears without an intact tympanic membrane

Mechanisms and prevention of cisplatinum-induced ototoxicity: a novel approach

OBJECTIVE To test the protective benefits of transtympanic Ringer's lactate in the prevention of cisplatinum-induced ototoxicitySETTING Ototoxicity is currently the most frequent dose-limiting side effect of cisplatinum chemotherapy. To date there is no protocol to prevent dose-related ototoxicity despite its prevalence and predictability. Previous animal studies have found lactate to be effective in the prevention of cisplatinum-induced ototoxicity.STUDY DESIGN Randomized, Prospective animal controlled trialSUBJECTS AND METHODS 70 chinchillas were exposed to systemic cisplatinum injected intraperitoneally. Injections were given in a single dose or divided in cycles in order to reach the targeted cumulative dosage of 16 mg/kg. Ototopical application of Ringer's lactate solution 0.2 ml twice per day during the chemotherapy application was performed. 10 guinea pigs were exposed to systemic cisplatinum injected intraperitoneally. Injections were given in two consecutive days at 10 mg/kg per day; to reach a cumulative dosage of 20 mg/kg. Transtympanic application of Ringer's lactate solution 0.2 ml per day during chemotherapy application was performed. Each animal had one experimental (Ringer's) and one control ear. Distortion Product Otoacoustic Emissions (DPOAE) between 1 and 16 kHz, Auditory Brainstem Responses (ABR) at 8, 15, 20 and 25 kHz, real time Polymerase Chain Reaction (rt-PCR), and scanning electron microscopy were performed to evaluate the protective effects of Ringer's lactate.RESULTS Ototopical application of Ringer's lactate solution in our established chinchilla animal model did not provide an otoprotective effect as measured by the DPOAE response and electron microscopy.CONCLUSION In our study the intratympanic application of Ringer's lactate solution through a tympanostomy ventilation tube did not provide an otoprotective effect. Further studies are needed to better assess the otoprotective or ototoxic effects of Ringer's lactate and other antioxidants on animal and human hearing.OBJECTIF Tester les effets protecteurs de la solution de lactate de Ringer trans tympanique dans la prévention de l'ototoxicité causée par le cisplatinum.CONTEXTE L'ototoxicité est présentement l'effet secondaire le plus fréquent qui limite la dose de chimiothérapie par le cisplatinum. À ce jour il n'existe pas de protocole pour prévenir l'ototoxicité reliée à la dose de cisplatinum, malgré sa prévalence et sa prédictibilité. Des études réalisées chez les animaux ont démontré que le lactate est efficace dans la prévention de l'ototoxicité causée par le cisplatinum.CONCEPTION DE L'ÉTUDE Essai animal prospectif, randomisé et à allocation aléatoire.SUJETS ET MÉTHODES 70 chinchillas ont été exposés au cisplatinum systémique injecté de façon intra péritonéale. Les injections ont été réalisées en une seule dose ou divisées en cycles afin d'atteindre la dose-cible cumulée de 16 mg/kg. Des applications ototopiques de 0.2 ml de soluté de lactate de Ringer ont été complétées deux fois par jour durant la chimiothérapie. Dix cochons d'inde ont été exposés au cisplatinum systémique injecté de façon intra péritonéale. Les injections ont été réalisées lors de deux journées consécutives à 10 mg/kg par jour afin d'atteindre la dose-cible cumulée de 20 mg/kg. L'application trans-tympanique du soluté 0.2 ml de lactate de Ringer a été complétée durant la chimiothérapie. Une oreille était expérimentale (lactate de Ringer) et une oreille était le contrôle chez chaque animal. Les produits de distorsion des émissions otoacoustiques entre 1 et 16 kHz, potentiels évoqués à 8, 15 20 et 25 kHz, l'amplification en chaîne par réaction en temps réel, et la microscopie électronique par balayage ont été complétés pour évaluer les effets protecteurs du lactate de Ringer.RÉSULTATS Les applications ototopiques du soluté de lactate de Ringer n'ont pas fourni un effet otoprotecteur dans notre modèle animal chinchilla tel que mesuré par les réponses aux produits de distorsion des émissions otoacoustiques et la microscopie électronique.CONCLUSION Dans cette étude l'application intra tympanique de soluté de lactate de Ringer au moyen de tubes de ventilation tympanotomique n'a pas fourni d'effet protecteur ototopique. D'autres études sont nécessaires pour mieux évaluer les effets otoprotecteurs ou ototoxiques du lactate de Ringer et d'autres antioxydants au niveau de l'audition chez les animaux et les humains

STRFs for LFP (left) and for MSU activity (right) averaged over electrodes in the two arrays that showed clear tuned spike activity.

<p>For the top two panels only 4 electrodes, indicated above the panel, produced clear STRFs for spikes. These were averaged. For the top panels array, the LFP-based STRF starts with a positive part followed by a negative part, whereas for the bottom panels (7 electrodes) the common negative-positive sequence is found. The initial positive LFP delays the spike firings for the top array, which occur on the negative going LFP phase. For the bottom array, spike activity occurs for LFP amplitudes that are at least 50% of negative maximum. Although both electrode arrays were in AI and at approximately the same depth, the differences in latencies are pronounced. Contour lines again indicate 25, 50 and 75% of LFP negative maximum (white) and positive maximum (red).</p

Correlation coefficient distance dependence.

<p>Scatterplot of the distance dependence of the natural log of the coherence-corrected peak cross-correlation coefficients for 2–16 Hz LFP-pairs (green symbols), 16–40 Hz LFP-pairs (Blue symbols), and spike-pairs (red symbols) recorded on the same electrodes. The slopes of the regression lines are steeper for the spike data compared to the LFP data.</p

Distance dependence of 2–40 Hz LFP-pair correlograms.

<p>In the left column, cross-correlation coefficient functions are show for all pairs from array 1 (top), array 2 (middle) and between electrodes located in different arrays (bottom). The second column shows the coherence-corrected correlograms. Note the extensive overlap of these correlograms. Note that the peak values in the correlogram are similar between arrays than within arrays. The fourth column upper two rows show the dependence of the corrected peak values as a function of distance for the within-array correlations; one notices only a moderate effect. The mean values are indicated with a thin line. The third column upper two rows show the change in peak cross-correlation coefficient as a function of electrode distance within an array. In the fourth column the corrected peak cross-correlation coefficients for spike-spike pairs are shown.</p

STRFs for LFP (left) and for MSU activity (right) averaged over the 16-electrode array.

<p>The two panels represent an average of the data shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0020046#pone-0020046-g005" target="_blank">Figure 5</a>. For the left panel blue indicates negative LFP amplitudes, red colors indicate positive amplitude values and yellow corresponds to zero crossings. Contour lines indicate 25, 50 and 75% of LFP negative maximum (white) and positive maximum (red). Note peak spike activity in the 50–75% negative LFP-amplitude contour lines.</p

Pearson product-moment correlation coefficients for marginal frequency distributions.

<p>Pearson product-moment correlation coefficients for marginal frequency distributions.</p

Example of STRFs determined on the basis of spikes and LFPs.

<p>STRFs determined on the basis of spikes are shown color coded and LFPs-based ones are indicated by white contour lines for negative levels at 75%, 50% and 25% of maximum, and red ones indicating positive levels. Same plotting conventions as for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0020046#pone-0020046-g004" target="_blank">Figure 4</a>. The frequency range in this example is from 1.2 kHz-40 kHz (5 octaves). As can be seen there are again only minor changes in the LFP profiles across the 8×2 electrode array, whereas the spike-based STRFs are more variable. Note that for a limited frequency range the LFP may start positive, thereby preventing or delaying the spike generation (channels 25 and 26, second row; channels 29 and 32, bottom row).</p