Douglas E. H. Hartley

Stimulus-timing-dependent plasticity of cortical frequency representation

Adult cortical circuits possess considerable plasticity, which can be induced by modifying their inputs. One mechanism proposed to underlie changes in neuronal responses is spike-timing-dependent plasticity (STDP), an up- or downregulation of synaptic efficacy contingent upon the order and timing of presynaptic and postsynaptic activity. The repetitive and asynchronous pairing of a sensory stimulus with either another sensory stimulus or current injection can alter the response properties of visual and somatosensory neurons in a manner consistent with STDP. To examine whether such plasticity also exists in the auditory system, we recorded from neurons in the primary auditory cortex of anesthetized and awake adult ferrets. The repetitive pairing of pure tones of different frequencies induced shifts in neuronal frequency selectivity, which exhibited a temporal specificity akin to STDP. Only pairs with stimulus onset asynchronies of 8 or 12 ms were effective and the direction of the shifts depended upon the order in which the tones within a pair were presented. Six hundred stimulus pairs (lasting ∼70 s) were enough to produce a significant shift in frequency tuning and the changes persisted for several minutes. The magnitude of the observed shifts was largest when the frequency separation of the conditioning stimuli was < ∼1 octave. Moreover, significant shifts were found only in the upper cortical layers. Our findings highlight the importance of millisecond-scale timing of sensory input in shaping neural function and strongly suggest STDP as a relevant mechanism for plasticity in the mature auditory system.

Combined electro-acoustic stimulation: a beneficial union?

Background:  The most pressing problem facing cochlear implant research is no longer making artificial hearing a reality. Instead, it is to develop devices that can more clearly reflect the capabilities of the human auditory system. Current cochlear implants rarely provide adequate pitch perception. As hearing loss commonly affects higher, more than lower frequencies, a possible solution is to preserve acoustic hearing at low frequencies by inserting a short electrode array and thus deliver combined electro‐acoustic stimulation (EAS).

Effects of conductive hearing loss on temporal aspects of sound transmission through the ear

Effects of conductive hearing loss on level and spectrum are well known. However, little is known about possible additional effects on temporal aspects of sound transmission. This study investigated effects of earplugs and middle ear effusions on amplitude and timing of cochlear microphonic (CM) responses in gerbils. Bilateral CM responses to pure tones (1-16 kHz) were monitored before and after (i). unilateral earplug insertion or (ii). injection of silicone oil, of various viscosities, into one middle ear. Earplugs produced flat hearing losses (mean 13 dB) and delayed CMs more at lower (mean 80 micros, 1-6 kHz) than at higher (20 micros, 8-16 kHz) frequencies. Effusions also produced flat hearing loss. On average, high viscosity effusions produced larger hearing losses (36 dB) than medium (25 dB) or low (20 dB) viscosity effusions. Low and medium viscosity effusions delayed responses to lower (mean 82 and 65 micros respectively, 1-6 kHz) more than to higher (mean 20 and 10 micros respectively, 8-16 kHz) frequencies. High viscosity effusions produced smaller delays across all frequencies (mean 31 micros, 1-16 kHz). In normal animals, CM responses were not delayed over a wide range of stimulus levels. Therefore, in addition to attenuation, conductive loss distorts acoustic temporal cues important for hearing.

Multisensory Training Improves Auditory Spatial Processing following Bilateral Cochlear Implantation

Cochlear implants (CIs) partially restore hearing to the deaf by directly stimulating the inner ear. In individuals fitted with CIs, lack of auditory experience due to loss of hearing before language acquisition can adversely impact outcomes. For example, adults with early-onset hearing loss generally do not integrate inputs from both ears effectively when fitted with bilateral CIs (BiCIs). Here, we used an animal model to investigate the effects of long-term deafness on auditory localization with BiCIs and approaches for promoting the use of binaural spatial cues. Ferrets were deafened either at the age of hearing onset or as adults. All animals were implanted in adulthood, either unilaterally or bilaterally, and were subsequently assessed for their ability to localize sound in the horizontal plane. The unilaterally implanted animals were unable to perform this task, regardless of the duration of deafness. Among animals with BiCIs, early-onset hearing loss was associated with poor auditory localization performance, compared with late-onset hearing loss. However, performance in the early-deafened group with BiCIs improved significantly after multisensory training with interleaved auditory and visual stimuli. We demonstrate a possible neural substrate for this by showing a training-induced improvement in the responsiveness of auditory cortical neurons and in their sensitivity to interaural level differences, the principal localization cue available to BiCI users. Importantly, our behavioral and physiological evidence demonstrates a facilitative role for vision in restoring auditory spatial processing following potential cross-modal reorganization. These findings support investigation of a similar training paradigm in human CI users.

Cortical cross-modal plasticity following deafness measured using functional near-infrared spectroscopy

Evidence from functional neuroimaging studies suggests that the auditory cortex can become more responsive to visual and somatosensory stimulation following deafness, and that this occurs predominately in the right hemisphere. Extensive cross-modal plasticity in prospective cochlear implant recipients is correlated with poor speech outcomes following implantation, highlighting the potential impact of central auditory plasticity on subsequent aural rehabilitation. Conversely, the effects of hearing restoration with a cochlear implant on cortical plasticity are less well understood, since the use of most neuroimaging techniques in CI recipients is either unsafe or problematic due to the electromagnetic artefacts generated by CI stimulation. Additionally, techniques such as functional magnetic resonance imaging (fMRI) are confounded by acoustic noise produced by the scanner that will be perceived more by hearing than by deaf individuals. Subsequently it is conceivable that auditory responses to acoustic noise produced by the MR scanner may mask auditory cortical responses to non-auditory stimulation, and render inter-group comparisons less significant. Uniquely, functional near-infrared spectroscopy (fNIRS) is a silent neuroimaging technique that is non-invasive and completely unaffected by the presence of a CI. Here, we used fNIRS to study temporal-lobe responses to auditory, visual and somatosensory stimuli in thirty profoundly-deaf participants and thirty normally-hearing controls. Compared with silence, acoustic noise stimuli elicited a significant group fNIRS response in the temporal region of normally-hearing individuals, which was not seen in profoundly-deaf participants. Visual motion elicited a larger group response within the right temporal lobe of profoundly-deaf participants, compared with normally-hearing controls. However, bilateral temporal lobe fNIRS activation to somatosensory stimulation was comparable in both groups. Using fNIRS these results confirm that auditory deprivation is associated with cross-modal plasticity of visual inputs to auditory cortex. Although we found no evidence for plasticity of somatosensory inputs, it is possible that our recordings may have included activation of somatosensory cortex that masked any group differences in auditory cortical responses due to the limited spatial resolution associated with fNIRS.

Bilateral cochlear implantation in the ferret: A novel animal model for behavioral studies

Bilateral cochlear implantation has recently been introduced with the aim of improving both speech perception in background noise and sound localization. Although evidence suggests that binaural perception is possible with two cochlear implants, results in humans are variable. To explore potential contributing factors to these variable outcomes, we have developed a behavioral animal model of bilateral cochlear implantation in a novel species, the ferret. Although ferrets are ideally suited to psychophysical and physiological assessments of binaural hearing, cochlear implantation has not been previously described in this species. This paper describes the techniques of deafening with aminoglycoside administration, surgical implantation of an intracochlear array and chronic intracochlear electrical stimulation with monitoring for electrode integrity and efficacy of stimulation. Experiments have been presented elsewhere to show that the model can be used to study behavioral and electrophysiological measures of binaural hearing in chronically implanted animals. This paper demonstrates that cochlear implantation and chronic intracochlear electrical stimulation are both safe and effective in ferrets, opening up the possibility of using this model to study potential protective effects of bilateral cochlear implantation on the developing central auditory pathway. Since ferrets can be used to assess psychophysical and physiological aspects of hearing along with the structure of the auditory pathway in the same animals, we anticipate that this model will help develop novel neuroprosthetic therapies for use in humans.

Speech-evoked activation in adult temporal cortex measured using functional near-infrared spectroscopy (fNIRS): Are the measurements reliable?

Functional near-infrared spectroscopy (fNIRS) is a silent, non-invasive neuroimaging technique that is potentially well suited to auditory research. However, the reliability of auditory-evoked activation measured using fNIRS is largely unknown. The present study investigated the test-retest reliability of speech-evoked fNIRS responses in normally-hearing adults. Seventeen participants underwent fNIRS imaging in two sessions separated by three months. In a block design, participants were presented with auditory speech, visual speech (silent speechreading), and audiovisual speech conditions. Optode arrays were placed bilaterally over the temporal lobes, targeting auditory brain regions. A range of established metrics was used to quantify the reproducibility of cortical activation patterns, as well as the amplitude and time course of the haemodynamic response within predefined regions of interest. The use of a signal processing algorithm designed to reduce the influence of systemic physiological signals was found to be crucial to achieving reliable detection of significant activation at the group level. For auditory speech (with or without visual cues), reliability was good to excellent at the group level, but highly variable among individuals. Temporal-lobe activation in response to visual speech was less reliable, especially in the right hemisphere. Consistent with previous reports, fNIRS reliability was improved by averaging across a small number of channels overlying a cortical region of interest. Overall, the present results confirm that fNIRS can measure speech-evoked auditory responses in adults that are highly reliable at the group level, and indicate that signal processing to reduce physiological noise may substantially improve the reliability of fNIRS measurements.

Effects of otitis media with effusion on central auditory function

Abstract Conductive hearing loss attenuates and delays sound passing through the middle ear. This impairs binaural hearing and other central auditory functions dependent on high fidelity sound transmission. Persistent conductive loss leads to central impairments that persist after the peripheral loss has resolved. For example, children who have had multiple episodes of otitis media with effusion (OME) in the first few years of life may have poor detection of sounds in noisy environments, evidenced by reduced binaural unmasking (BU). Recent research shows that a ‘threshold’ level of OME is required to produce impaired BU. Children who had OME in one or both ears for more than about 50% of the first 5 years had reduced BU. Animal research, using long-term ear plugging, suggests that total OME duration, rather than age at the time of having the disease, determines its effect on BU. Animals reared with bilateral (but not unilateral) ear plugs also have poor auditory temporal resolution, and reduced sensitivity to short tones in the presence of background noise, after plug removal. However, given time (6–24 months) and training, all animals regained normal temporal resolution.

Plasticity in bilateral superior temporal cortex: effects of deafness and cochlear implantation on auditory and visual speech processing

ABSTRACT While many individuals can benefit substantially from cochlear implantation, the ability to perceive and understand auditory speech with a cochlear implant (CI) remains highly variable amongst adult recipients. Importantly, auditory performance with a CI cannot be reliably predicted based solely on routinely obtained information regarding clinical characteristics of the CI candidate. This review argues that central factors, notably cortical function and plasticity, should also be considered as important contributors to the observed individual variability in CI outcome. Superior temporal cortex (STC), including auditory association areas, plays a crucial role in the processing of auditory and visual speech information. The current review considers evidence of cortical plasticity within bilateral STC, and how these effects may explain variability in CI outcome. Furthermore, evidence of audio‐visual interactions in temporal and occipital cortices is examined, and relation to CI outcome is discussed. To date, longitudinal examination of changes in cortical function and plasticity over the period of rehabilitation with a CI has been restricted by methodological challenges. The application of functional near‐infrared spectroscopy (fNIRS) in studying cortical function in CI users is becoming increasingly recognised as a potential solution to these problems. Here we suggest that fNIRS offers a powerful neuroimaging tool to elucidate the relationship between audio‐visual interactions, cortical plasticity during deafness and following cochlear implantation, and individual variability in auditory performance with a CI. HighlightsPlasticity in left and right temporal regions may impact differently on CI outcome.Speechreading may guard against maladaptive plasticity in left phonological areas.Left hemisphere audio‐visual interactions may facilitate auditory recovery with a CI.Right hemisphere cross‐modal plasticity is associated with poor CI outcome.fNIRS can assess cortical activation with a CI that may help to predict CI success.

The use of functional near-infrared spectroscopy for measuring cortical reorganisation in cochlear implant users: A possible predictor of variable speech outcomes?

Continued developments in cochlear implantation have enabled a majority of patients to benefit substantially from their cochlear implant (CI) and to achieve a good level of speech understanding. However, some people receive less benefit from their implant than others, and large variability still exists in how well individuals can understand speech through their CI (Lazard et al., 2012). While some influential factors have been identified, including age at onset of hearing loss, the duration of deafness, and duration of CI experience, currently there is no accurate predictor of how well an individual will perform with a CI (Lazard et al., 2012). However, a better understanding of the mechanisms underlying the variability in CI outcome is of clinical importance. This information may inform clinicians in counselling patients prior to implantation about their likely experiences with a CI and to help shape the rehabilitation that they receive post-implantation. It could also help to identify those individuals who are most likely to benefit from a CI, helping to ensure that limited healthcare resources are directed effectively. Emerging evidence suggests that ‘cross-modal’ reorganization of auditory brain regions could be an important factor in understanding and predicting how much benefit an individual will receive from their CI. Following deafness, cortical areas that would usually process auditory information can reorganize and become more sensitive to the intact senses, such as vision (see Fig. 1). The extent of this visual takeover of auditory brain regions may affect the ability of a CI recipient to process auditory information from their implant effectively. For example, Sandmann et al. (2012) demonstrated an inverse relationship between the response of right auditory cortex to a visual chequerboard stimulus and auditory speech perception scores. That is, a high level of visual takeover of auditory brain regions may be predictive of a poor CI outcome. As well as these changing responses to non-linguistic, ‘low-level’ visual stimuli, it is important to understand how auditory deprivation and subsequent implantation impact on the processing of ‘high-level’ stimuli like speech. It is widely accepted that everyday speech perception is multimodal in nature: auditory and visual speech cues are integrated to form a unified percept. Cross-modal interactions in speech processing are observed in healthy individuals both behaviourally and at the cortical level. For instance, research has revealed responses to visual speech information (in silence) in the auditory cortex of normal hearing individuals (Calvert et al., 1997). In a similar population, responses to auditory speech information have been found in the visual cortex (Giraud and Truy, 2002). While cross-modal interactions in speech perception are therefore the norm, it is thought that this inherent synergy between auditory and visual speech might be altered in deaf individuals and in CI recipients, in a way that may benefit perception. It has been proposed that individuals with a CI rely on a heightened synergy between audition and vision. For example, Giraud et al. (2001) found that CI users Correspondence to: Carly A Lawler, NIHR Nottingham Hearing Biomedical Research Unit, Ropewalk House, 113 The Ropewalk, Nottingham NG1 5DU. Email: msxca1@nottingham.ac.uk