Positron Emission Tomography Imaging Reveals Auditory and Frontal Cortical Regions Involved with Speech Perception and Loudness Adaptation

Considerable progress has been made in the treatment of hearing loss with auditory implants. However, there are still many implanted patients that experience hearing deficiencies, such as limited speech understanding or vanishing perception with continuous stimulation (i.e., abnormal loudness adaptation). The present study aims to identify specific patterns of cerebral cortex activity involved with such deficiencies. We performed O-15-water positron emission tomography (PET) in patients implanted with electrodes within the cochlea, brainstem, or midbrain to investigate the pattern of cortical activation in response to speech or continuous multi-tone stimuli directly inputted into the implant processor that then delivered electrical patterns through those electrodes. Statistical parametric mapping was performed on a single subject basis. Better speech understanding was correlated with a larger extent of bilateral auditory cortex activation. In contrast to speech, the continuous multi-tone stimulus elicited mainly unilateral auditory cortical activity in which greater loudness adaptation corresponded to weaker activation and even deactivation. Interestingly, greater loudness adaptation was correlated with stronger activity within the ventral prefrontal cortex, which could be up-regulated to suppress the irrelevant or aberrant signals into the auditory cortex. The ability to detect these specific cortical patterns and differences across patients and stimuli demonstrates the potential for using PET to diagnose auditory function or dysfunction in implant patients, which in turn could guide the development of appropriate stimulation strategies for improving hearing rehabilitation. Beyond hearing restoration, our study also reveals a potential role of the frontal cortex in suppressing irrelevant or aberrant activity within the auditory cortex, and thus may be relevant for understanding and treating tinnitus

Remixing music using source separation algorithms to improve the musical experience of cochlear implant users

Music perception remains rather poor for many Cochlear Implant (CI) users due to the users' deficient pitch perception. However, comprehensible vocals and simple music structures are well perceived by many CI users. In previous studies researchers re-mixed songs to make music more enjoyable for them, favoring the preferred music elements (vocals or beat) attenuating the others. However, mixing music requires the individually recorded tracks (multitracks) which are usually not accessible. To overcome this limitation, Source Separation (SS) techniques are proposed to estimate the multitracks. These estimated multitracks are further re-mixed to create more pleasant music for CI users. However, SS may introduce undesirable audible distortions and artifacts. Experiments conducted with CI users (N = 9) and normal hearing listeners (N = 9) show that CI users can have different mixing preferences than normal hearing listeners. Moreover, it is shown that CI users' mixing preferences are user dependent. It is also shown that SS methods can be successfully used to create preferred re-mixes although distortions and artifacts are present. Finally, CI users' preferences are used to propose a benchmark that defines the maximum acceptable levels of SS distortion and artifacts for two different mixes proposed by CI users.This work was supported by the DFG Cluster of Excellence EXC 1077/1 “Hearing4all.

Investigation of a new electrode array technology for a central auditory prosthesis.

Ongoing clinical studies on patients recently implanted with the auditory midbrain implant (AMI) into the inferior colliculus (IC) for hearing restoration have shown that these patients do not achieve performance levels comparable to cochlear implant patients. The AMI consists of a single-shank array (20 electrodes) for stimulation along the tonotopic axis of the IC. Recent findings suggest that one major limitation in AMI performance is the inability to sufficiently activate neurons across the three-dimensional (3-D) IC. Unfortunately, there are no currently available 3-D array technologies that can be used for clinical applications. More recently, there has been a new initiative by the European Commission to fund and develop 3-D chronic electrode arrays for science and clinical applications through the NeuroProbes project that can overcome the bulkiness and limited 3-D configurations of currently available array technologies. As part of the NeuroProbes initiative, we investigated whether their new array technology could be potentially used for future AMI patients. Since the NeuroProbes technology had not yet been tested for electrical stimulation in an in vivo animal preparation, we performed experiments in ketamine-anesthetized guinea pigs in which we inserted and stimulated a NeuroProbes array within the IC and recorded the corresponding neural activation within the auditory cortex. We used 2-D arrays for this initial feasibility study since they were already available and were sufficient to access the IC and also demonstrate effective activation of the central auditory system. Based on these encouraging results and the ability to develop customized 3-D arrays with the NeuroProbes technology, we can further investigate different stimulation patterns across the ICC to improve AMI performance

Rate growth curves recorded from A1 and pooled from all 12 stimulated NP sites.

<p>A) Growth rate of LFP peak magnitude versus stimulus level (in dB relative to 1 µA). B) Growth rate of LFP area versus stimulus level. C) Growth rate for multi-unit spikes versus stimulus level.</p

Raw data and PSTH plots.

<p>A) Averaged unfiltered raw data (20 sweeps) showing LFP in response to stimulation with an NP site from 20 to 52 dB relative to 1 µA (actual stimuli were 12–52 dB in 2-dB steps). The monotonic increase in LFP size with stimulation amplitude is evident. The LFP threshold is 28 dB in this example. B) PSTHs corresponding to the different stimulation levels indicated in each plot. PSTH bars represent 1 ms bins. The dotted line indicates stimulus onset at 0 ms. Bottom right trace is a single trial filtered for spikes with the artifact removed and showing multi-unit activity in response to a stimulation at 52 dB. Each detected spike is marked by an * with the red line indicating threshold for spike detection. The MUA threshold is 34 dB, which is higher than the LFP threshold.</p

Comb-like, silicon-based NeuroProbes array with four 10-mm-long probe shafts separated by 400 µm.

<p>Each shank is comprised of eight IrOx electrode sites. The array is interconnected to a highly flexible polyimide ribbon cable interfacing with a zero insertion force (ZIF) connector on a printed circuit board (PCB) that was connected to the stimulator. For probe insertion, the probe comb is fixed adhesively to the insertion plate and attached to a micromanipulator. The 100-µm-thick probe shanks proved to be stiff enough for insertion into deep brain structures.</p

Modeled safe stimulation parameters.

<p>Stimulation above the solid black line (k = 2) has been shown to induce tissue damage and co-varies with total charge and charge density per pulse phase. The curves with different symbols reflect how charge density changes with increasing charge per phase for either the NP or AMI sites, i.e., for different site areas, for three different pulse widths each. The local field potential (LFP, red dot, 200 µs/phase) and spike (Spk, blue dot, 200 µs/phase) thresholds obtained from animal studies are labeled on the plot for direct comparison.</p

Diploid hepatocytes drive physiological liver renewal in adult humans

Physiological liver cell replacement is central to maintaining the organ's high metabolic activity, although its characteristics are difficult to study in humans. Using retrospective radiocarbon (C-14) birth dating of cells, we report that human hepatocytes show continuous and lifelong turnover, allowing the liver to remain a young organ (average age &lt;3 years). Hepatocyte renewal is highly dependent on the ploidy level. Diploid hepatocytes show more than 7-fold higher annual birth rates than polyploid hepatocytes. These observations support the view that physiological liver cell renewal in humans is mainly dependent on diploid hepatocytes, whereas polyploid cells are compromised in their ability to divide. Moreover, cellular transitions between diploid and polyploid hepatocytes are limited under homeostatic conditions. With these findings, we present an integrated model of homeostatic liver cell generation in humans that provides fundamental insights into liver cell turnover dynamics