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

Transient reduction of tinnitus intensity is marked by concomitant reductions of delta band power

<p>Abstract</p> <p>Background</p> <p>Tinnitus is an auditory phantom phenomenon characterized by the sensation of sounds without objectively identifiable sound sources. To date, its causes are not well understood. Previous research found altered patterns of spontaneous brain activity in chronic tinnitus sufferers compared to healthy controls, yet it is unknown whether these abnormal oscillatory patterns are causally related to the tinnitus sensation. Partial support for this notion comes from a neurofeedback approach developed by our group, in which significant reductions in tinnitus loudness could be achieved in patients who successfully normalized their patterns of spontaneous brain activity. The current work attempts to complement these studies by scrutinizing how modulations of tinnitus intensity alter ongoing oscillatory activity.</p> <p>Results</p> <p>In the present study the relation between tinnitus sensation and spontaneous brain activity was investigated using residual inhibition (RI) to reduce tinnitus intensity and source-space projected magnetencephalographic (MEG) data to index brain activity. RI is the sustained reduction (criteria: 50% for at least 30 s) in tinnitus loudness after cessation of a tonal tinnitus masker. A pilot study (n = 38) identified 10 patients who showed RI. A significant reduction of power in the delta (1.3–4.0 Hz) frequency band was observed in temporal regions during RI (p ≤ 0.001).</p> <p>Conclusion</p> <p>The current results suggest that changes of tinnitus intensity induced by RI are mediated by alterations in the pathological patterns of spontaneous brain activity, specifically a reduction of delta activity. Delta activity is a characteristic oscillatory activity generated by deafferented/deprived neuronal networks. This implies that RI effects might reflect the transient reestablishment of balance between excitatory and inhibitory neuronal assemblies, via reafferentation, that have been perturbed (in most tinnitus individuals) by hearing damage. As enhancements have been reported in the delta frequency band for tinnitus at rest, this result conforms to our assumption that a normalization of oscillatory properties of cortical networks is a prerequisite for attenuating the tinnitus sensation. For RI to have therapeutic significance however, this normalization would have to be stabilized.</p

Unanesthetized Auditory Cortex Exhibits Multiple Codes for Gaps in Cochlear Implant Pulse Trains

Cochlear implant listeners receive auditory stimulation through amplitude-modulated electric pulse trains. Auditory nerve studies in animals demonstrate qualitatively different patterns of firing elicited by low versus high pulse rates, suggesting that stimulus pulse rate might influence the transmission of temporal information through the auditory pathway. We tested in awake guinea pigs the temporal acuity of auditory cortical neurons for gaps in cochlear implant pulse trains. Consistent with results using anesthetized conditions, temporal acuity improved with increasing pulse rates. Unlike the anesthetized condition, however, cortical neurons responded in the awake state to multiple distinct features of the gap-containing pulse trains, with the dominant features varying with stimulus pulse rate. Responses to the onset of the trailing pulse train (Trail-ON) provided the most sensitive gap detection at 1,017 and 4,069 pulse-per-second (pps) rates, particularly for short (25 ms) leading pulse trains. In contrast, under conditions of 254 pps rate and long (200 ms) leading pulse trains, a sizeable fraction of units demonstrated greater temporal acuity in the form of robust responses to the offsets of the leading pulse train (Lead-OFF). Finally, TONIC responses exhibited decrements in firing rate during gaps, but were rarely the most sensitive feature. Unlike results from anesthetized conditions, temporal acuity of the most sensitive units was nearly as sharp for brief as for long leading bursts. The differences in stimulus coding across pulse rates likely originate from pulse rate-dependent variations in adaptation in the auditory nerve. Two marked differences from responses to acoustic stimulation were: first, Trail-ON responses to 4,069 pps trains encoded substantially shorter gaps than have been observed with acoustic stimuli; and second, the Lead-OFF gap coding seen for <15 ms gaps in 254 pps stimuli is not seen in responses to sounds. The current results may help to explain why moderate pulse rates around 1,000 pps are favored by many cochlear implant listeners

Fitting model of ABR age dependency in a clinical population of normal hearing children

The purpose of this study was to present a simple and powerful fitting model that describes age-dependent changes of auditory brainstem responses (ABR) in a clinical population of normal hearing children. A total of 175 children (younger than 200 weeks postconceptional age) were referred for audiologic assessment with normal ABR results. ABR parameters of normal hearing children between 2003 and 2008 were included. The results of the right ears recorded at 90 dB nHL were analyzed. A simple and accurate fitting model was formulated based on these data. A very similar age-dependent effect was found for peaks III and V, and I–III and I–V intervals; latencies decrease as postconceptional age increases. It shows that the total age-dependent effect will be completed after 1.5–2 years. The age-dependent effect can be modeled by a relatively simple and accurate exponential function. This fitting model can be easily implemented to analyze ABR results of infants in daily clinical practice. We speculate about the underlying physiological processes

Neural mechanisms of interstimulus interval-dependent responses in the primary auditory cortex of awake cats

<p>Abstract</p> <p>Background</p> <p>Primary auditory cortex (AI) neurons show qualitatively distinct response features to successive acoustic signals depending on the inter-stimulus intervals (ISI). Such ISI-dependent AI responses are believed to underlie, at least partially, categorical perception of click trains (elemental vs. fused quality) and stop consonant-vowel syllables (eg.,/da/-/ta/continuum).</p> <p>Methods</p> <p>Single unit recordings were conducted on 116 AI neurons in awake cats. Rectangular clicks were presented either alone (single click paradigm) or in a train fashion with variable ISI (2–480 ms) (click-train paradigm). Response features of AI neurons were quantified as a function of ISI: one measure was related to the degree of stimulus locking (temporal modulation transfer function [tMTF]) and another measure was based on firing rate (rate modulation transfer function [rMTF]). An additional modeling study was performed to gain insight into neurophysiological bases of the observed responses.</p> <p>Results</p> <p>In the click-train paradigm, the majority of the AI neurons ("synchronization type"; <it>n </it>= 72) showed stimulus-locking responses at long ISIs. The shorter cutoff ISI for stimulus-locking responses was on average ~30 ms and was level tolerant in accordance with the perceptual boundary of click trains and of consonant-vowel syllables. The shape of tMTF of those neurons was either band-pass or low-pass. The single click paradigm revealed, at maximum, four response periods in the following order: 1st excitation, 1st suppression, 2nd excitation then 2nd suppression. The 1st excitation and 1st suppression was found exclusively in the synchronization type, implying that the temporal interplay between excitation and suppression underlies stimulus-locking responses. Among these neurons, those showing the 2nd suppression had band-pass tMTF whereas those with low-pass tMTF never showed the 2nd suppression, implying that tMTF shape is mediated through the 2nd suppression. The recovery time course of excitability suggested the involvement of short-term plasticity. The observed phenomena were well captured by a single cell model which incorporated AMPA, GABA_A, NMDA and GABA_Breceptors as well as short-term plasticity of thalamocortical synaptic connections.</p> <p>Conclusion</p> <p>Overall, it was suggested that ISI-dependent responses of the majority of AI neurons are configured through the temporal interplay of excitation and suppression (inhibition) along with short-term plasticity.</p

Incidence and clinical value of prolonged I–V interval in NICU infants after failing neonatal hearing screening

Infants admitted to neonatal intensive care units (NICUs) have a higher incidence of perinatal complications and delayed maturational processes. Parameters of the auditory brainstem response (ABR) were analyzed to study the prevalence of delayed auditory maturation or neural pathology. The prevalence of prolonged I–V interval as a measure of delayed maturation and the correlation with ABR thresholds were investigated. All infants admitted to the NICU Sophia Children’s Hospital between 2004 and 2009 who had been referred for ABR measurement after failing neonatal hearing screening with automated auditory brainstem response (AABR) were included. The ABR parameters were retrospectively analyzed. Between 2004 and 2009, 103 infants were included: 46 girls and 57 boys. In 58.3% (60 infants) of our population, the I–V interval was recordable in at least one ear at first diagnostic ABR measurement. In 4.9%, the I–V interval was severely prolonged. The median ABR threshold of infants with a normal or mildly prolonged I–V interval was 50 dB. The median ABR threshold of infants with a severely prolonged I–V interval was 30 dB. In conclusion, in case both peak I and V were measurable, we found only a limited (4.9%) incidence of severely prolonged I–V interval (≥0.8 ms) in this high-risk NICU population. A mild delay in maturation is a more probable explanation than major audiologic or neural pathology, as ABR thresholds were near normal in these infants

Encoding of Temporal Information by Timing, Rate, and Place in Cat Auditory Cortex

A central goal in auditory neuroscience is to understand the neural coding of species-specific communication and human speech sounds. Low-rate repetitive sounds are elemental features of communication sounds, and core auditory cortical regions have been implicated in processing these information-bearing elements. Repetitive sounds could be encoded by at least three neural response properties: 1) the event-locked spike-timing precision, 2) the mean firing rate, and 3) the interspike interval (ISI). To determine how well these response aspects capture information about the repetition rate stimulus, we measured local group responses of cortical neurons in cat anterior auditory field (AAF) to click trains and calculated their mutual information based on these different codes. ISIs of the multiunit responses carried substantially higher information about low repetition rates than either spike-timing precision or firing rate. Combining firing rate and ISI codes was synergistic and captured modestly more repetition information. Spatial distribution analyses showed distinct local clustering properties for each encoding scheme for repetition information indicative of a place code. Diversity in local processing emphasis and distribution of different repetition rate codes across AAF may give rise to concurrent feed-forward processing streams that contribute differently to higher-order sound analysis

Short and Intense Tailor-Made Notched Music Training against Tinnitus: The Tinnitus Frequency Matters

Tinnitus is one of the most common diseases in industrialized countries. Here, we developed and evaluated a short-term (5 subsequent days) and intensive (6 hours/day) tailor-made notched music training (TMNMT) for patients suffering from chronic, tonal tinnitus. We evaluated (i) the TMNMT efficacy in terms of behavioral and magnetoencephalographic outcome measures for two matched patient groups with either low (≤8 kHz, N = 10) or high (>8 kHz, N = 10) tinnitus frequencies, and the (ii) persistency of the TMNMT effects over the course of a four weeks post-training phase. The results indicated that the short-term intensive TMNMT took effect in patients with tinnitus frequencies ≤8 kHz: subjective tinnitus loudness, tinnitus-related distress, and tinnitus-related auditory cortex evoked activity were significantly reduced after TMNMT completion. However, in the patients with tinnitus frequencies >8 kHz, significant changes were not observed. Interpreted in their entirety, the results also indicated that the induced changes in auditory cortex evoked neuronal activity and tinnitus loudness were not persistent, encouraging the application of the TMNMT as a longer-term training. The findings are essential in guiding the intended transfer of this neuro-scientific treatment approach into routine clinical practice

Radiotherapy for Soft Tissue Sarcomas after Isolated Limb Perfusion and Surgical Resection: Essential for Local Control in All Patients?

Background: Standard treatment for localized soft tissue sarcoma (STS) is resection plus adjuvant radiotherapy (RTx). In approximately 10% of cases, resection would cause severe loss of function or even require amputation because of the extent of disease. Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF-α) and melphalan can achieve regression of the tumor, facilitating limb-saving resection. RTx improves local control but may lead to increased morbidity. Methods: In our database of over 500 ILPs, 122 patients with unifocal STS were treated by ILP followed by limb-sparing surgery. All included patients were candidates for amputation. Results: Surgery resulted in 69 R0 resections (57%), and in 53 specimens (43%) resection margins contained microscopic evidence of tumor (R1). Histopathological examination revealed >50% ILP-induced tumor necrosis in 59 cases (48%). RTx was administered in 73 patients (60%). Local recurrence rate was 21% after median follow-up of 31 months (2-182 months). Recurrence was significantly less in patients with >50% ILP-induced necrosis versus ≤50% necrosis (7% vs. 33%, P = 0.001). A similar significant correlation was observed for R0 versus R1 resections (15% vs. 28%, P = 0.04). In 36 patients with R0 resection and >50% necrosis, of whom 21 were spared RTx, no recurrences were observed during follow-up. Conclusions: In patients with locally advanced primary STS, treated with ILP followed by R0 resection, and with >50% ILP-induced necrosis in the resected specimen, RTx is of no further benefit

Similarity of Traveling-Wave Delays in the Hearing Organs of Humans and Other Tetrapods

Transduction of sound in mammalian ears is mediated by basilar-membrane waves exhibiting delays that increase systematically with distance from the cochlear base. Most contemporary accounts of such “traveling-wave” delays in humans have ignored postmortem basilar-membrane measurements in favor of indirect in vivo estimates derived from brainstem-evoked responses, compound action potentials, and otoacoustic emissions. Here, we show that those indirect delay estimates are either flawed or inadequately calibrated. In particular, we argue against assertions based on indirect estimates that basilar-membrane delays are much longer in humans than in experimental animals. We also estimate in vivo basilar-membrane delays in humans by correcting postmortem measurements in humans according to the effects of death on basilar-membrane vibrations in other mammalian species. The estimated in vivo basilar-membrane delays in humans are similar to delays in the hearing organs of other tetrapods, including those in which basilar membranes do not sustain traveling waves or that lack basilar membranes altogether