Biology subjects

Bizley, J. K.

Publications and source records attributed to Bizley, J. K..

18 recordsLinked to original sources

bioRxiv2026

Cortical cooling reveals a role for visual cortex in generating visual responses in auditory cortex

Multisensory integration is a fundamental feature of cortical processing, yet the functional pathways that deliver visual signals to the auditory cortex remain poorly understood. While anatomical studies reveal multiple candidate projection routes, demonstrating their causal contribution requires targeted manipulation of neural activity. Here, we used cortical cooling to reversibly inactivate the posteromedial lateral suprasylvian cortex (PMLS) and the adjacent area 21 to determine the functional role of higher-order visual areas in generating visual responses within the auditory cortex of the ferret. Units responsive to sound, light, or combined audiovisual stimuli were found across all sampled auditory fields and cortical depths, with visual responses most prominent within the infragranular layers and the non-tonotopic secondary auditory cortex of the Anterior Ectosylvian Gyrus (AEG). Cortical cooling induced robust, bi-directional, and stimulus-specific modulations of firing rates in AC. Approximately 50% of visually responsive units exhibited a significant decrease or complete elimination of visual activity during cooling, confirming a functional role for visual input from PLMS/area 21 to AC. Surprisingly, cooling also revealed circuit-level complexities: a subset ([~]5%) of units showed enhanced or newly emergent visual responses during inactivation, suggesting that PMLS/area 21 normally exerts a gating influence over alternative visual pathways. Furthermore, contrary to feedforward anatomical predictions, neurons in the AEG--the region most heavily innervated by the cooled visual areas --were less frequently impacted by cooling than those in PEG. Together, these findings demonstrate that higher visual areas causally shape cross-modal processing in the auditory cortex through a complex mixture of direct excitation and network-level modulation.

neuroscience↗

bioRxiv2025

Head-Centred Sound Localisation Behaviour Reveals Head and World Centered Reference Frames in Auditory Cortex

The auditory system relies on head-centered localisation cues to estimate sound source position. Yet listeners and single neurons can encode sound in world-centred spatial reference frames. However, most studies of sound localisation constrain the subjects orientation within a fixed speaker ring, making it difficult to distinguish which reference frame underlies spatial coding. We utilised a sound localisation task that required ferrets localise sound location, relative to the head, across rotations in the starting platform within the testing arena. Two ferrets were trained to discriminate front from back sounds. Once trained, the orientation of both the central platform and the target speakers were rotated between testing sessions, retaining the task contingency in head-centered coordinates, but breaking the alignment of head and world centered reference frames. Probe trials were presented from the other speakers so that spatial receptive fields could be constructed and compared across central platform rotations. Neural activity was recorded from auditory cortex using chronically implanted 32-channel arrays. Across 1,777 recorded units, 596 were stimulus driven. Spatially tuned neurons were predominantly head-centred, with 208 and 232 units classified as head-centred in the two animals, compared with 48 and 49 world-centred units and 33 and 26 un-tuned units, respectively. Temporal analysis showed that most units retained the same reference-frame classification from onset to offset, but the magnitude of their head-versus-world preference diminished over time, with offset responses shifting towards more ambiguous and, in some cases, world-centred coding. Together, these results demonstrate that auditory cortex maintains parallel head centered and allocentric representations that are head dominated at onset but incorporate increased world-centred information at offset, supporting perceptual constancy during dynamic listening.

neuroscience↗

bioRxiv2025

Visual contributions to the perception of speech in noise

Investigations of the role of audiovisual integration in speech-in-noise perception have largely focused on the benefits provided by lipreading cues. Nonetheless, audiovisual temporal coherence can offer a complementary advantage in auditory selective attention tasks. We developed an audiovisual speech-in-noise test to assess the benefit of visually conveyed phonetic information and visual contributions to auditory streaming. The test was a video version of the Childrens Coordinate Response Measure with a noun as the second keyword (vCCRMn). The vCCRMn allowed us to measure speech reception thresholds in the presence of two competing talkers under three visual conditions: a full naturalistic video (AV), a video which was interrupted during the target word presentation (Inter), thus, providing no lipreading cues, and a static image of a talker with audio only (A). In each case, the video/image could display either the target talker, or one of the two competing maskers. We assessed speech reception thresholds in each visual condition in 37 young ([≤] 35 years old) normal-hearing participants. Lipreading ability was independently assessed with the Test of Adult Speechreading (TAS). Results showed that both target-coherent AV and Inter visual conditions offer participants a listening benefit over the static image audio-only condition, with the full AV target-coherent condition providing the most benefit. Lipreading ability correlated with the audiovisual benefit shown in the full AV target-coherent condition, but not the benefit in the Inter target-coherent condition. Together our results are consistent with visual information providing independent benefits to listening, through lip reading and enhanced auditory streaming.

neuroscience↗

bioRxiv2025

Auditory regularity detection in the ferret

Acoustic sequences that transition from random to regularly repeating tones are increasingly used to study how the auditory system detects structure. Humans can identify such regularities rapidly, often within a single cycle. To test whether this ability is unique to humans, we trained ferrets (n = 6) to detect transitions from random tone sequences to repeating patterns. All animals learned the task and showed high accuracy for short (3 tone) patterns. Performance remained above chance for longer patterns (5 or 7 tones), though accuracy declined with increased pattern length. In a control condition where both random and regular segments contained the same five frequencies, ferrets continued to detect regularity, indicating they relied on temporal patterning rather than spectral content. To further rule out spectral cues, we included transitions from random 20 tone sequences to random 3, 5 or 7 tone sequences without repetition. Although these stimuli elicited performance above the false alarm rate seen in fully random trials, detection accuracy remained substantially lower than that observed for regular sequences. This suggests ferrets were not solely detecting changes in spectral statistics, but true regularity. Together, our results indicate that sensitivity to regular patterns within sound is not unique to humans and may reflect a broader auditory computation shared across species.

animal behavior and cognition↗

bioRxiv2023

Auditory training alters the cortical representation of both learned and task irrelevant sound features

Auditory learning is supported by long-term changes in the neural processing of sound. We examined these task-depend changes in auditory cortex by mapping neural sensitivity to timbre, pitch and location cues in trained ferrets (n = 5), and untrained control ferrets (n = 5). Trained animals either identified vowels in a two-alternative forced choice task (n = 3) or discriminated when a repeating vowel changed in identity or pitch (n = 2). Neural responses were recorded under anesthesia in two primary auditory cortical fields and two tonotopically organized non-primary fields. In trained animals, the overall sensitivity to sound timbre was reduced across three cortical fields compared to control animals, but maintained in a non-primary field (the posterior pseudosylvian field). While training did not increase sensitivity to timbre across auditory cortex, it did change the way in which neurons integrated spectral information with neural responses in trained animals increasing their sensitivity to first and second formant frequencies,, whereas in control animals cortical sensitivity to spectral timbre depends mostly on the second formant. Animals trained on timbre identification were required to generalize across pitch when discriminating timbre and their neurons became less modulated by fundamental frequency relative to control animals. Finally, both trained groups showed increased spatial sensitivity and an enhanced response to sound source locations close to the midline, where the loudspeaker was located in the training chamber. These results demonstrate that training elicited widespread alterations in the cortical representation of complex sounds.

neuroscience↗

bioRxiv2023

Gradient boosted decision trees reveal nuances of auditory discrimination behaviour

Animal psychophysics can generate rich behavioral datasets, often comprised of many 1000s of trials for an individual subject. Gradient-boosted models are a promising machine learning approach for analyzing such data, partly due to the tools that allow users to gain insight into how the model makes predictions. We trained ferrets to report a target words presence, timing, and lateralization within a stream of consecutively presented non-target words. To assess the animals ability to generalize across pitch, we manipulated the fundamental frequency (F0) of the speech stimuli across trials, and to assess the contribution of pitch to streaming, we roved the F0 from word token-to-token. We then implemented gradient-boosted regression and decision trees on the trial outcome and reaction time data to understand the behavioral factors behind the ferrets decision-making. We visualized model contributions by implementing SHAPs feature importance and partial dependency plots. While ferrets could accurately perform the task across all pitch-shifted conditions, our models reveal subtle effects of shifting F0 on performance, with within-trial pitch shifting elevating false alarms and extending reaction times. Our models identified a subset of non-target words that animals commonly false alarmed to. Follow-up analysis demonstrated that the spectrotemporal similarity of target and non-target words rather than similarity in duration or amplitude waveform was the strongest predictor of the likelihood of false alarming. Finally, we compared the results with those obtained with traditional mixed effects models, revealing equivalent or better performance for the gradient-boosted models over these approaches. AUTHOR SUMMARYThe sorts of listening challenges faced by real-world listeners are rarely captured by most laboratory-based auditory paradigms, particularly those testing animal models. However, many labs are attempting to utilize more realistic experiments, and more complicated behavioral paradigms require more sophisticated approaches to analyzing the resulting data. Here, we used a new behavioral paradigm to test the ability of ferret listeners to identify target speech sounds and assess their ability to generalize across changes in pitch. To make sense of the resulting dataset, we used machine learning algorithms to understand how trained ferrets perform this task. Gradient-boosted regression and decision trees are well-established machine learning methods that do not require users to predetermine interaction effects and are accompanied by visualization methods that allow insights to be gained into how multiple factors ultimately shape behavior. We compare the use of gradient-boosted models to more standard regression approaches and, by applying these methods, we demonstrate key features of ferrets performance on this task. Our results suggest that this machine learning approach is ideal for analyzing behavioral data in animal models.

neuroscience↗

bioRxiv2022

Dissociable neural correlates of multisensory coherence and selective attention

Previous work has demonstrated that performance in an auditory selective attention task can be enhanced or impaired, depending on whether a task-irrelevant visual stimulus is temporally coherent with a target auditory stream or with a competing distractor. However, it remains unclear how audiovisual (AV) temporal coherence and auditory selective attention interact at the neurophysiological level. Here, we measured neural activity using electroencephalography (EEG) while participants performed an auditory selective attention task, detecting deviants in a target audio stream. The amplitude envelope of the two competing auditory streams changed independently, while the radius of a visual disc was manipulated to control the audiovisual coherence. Analysis of the neural responses to the sound envelope demonstrated that auditory responses were enhanced independently of the attentional condition: both target and masker stream responses were enhanced when temporally coherent with the visual stimulus. In contrast, attention enhanced the event-related response (ERP) evoked by the transient deviants, independently of AV coherence. Finally, we identified a spatiotemporal component of the ERP, likely originating from the superior temporal gyrus and the frontoparietal network, in which both attention and coherence synergistically modulated ERP amplitude. These results provide evidence for dissociable neural signatures of bottom-up (coherence) and top-down (attention) effects in the AV object formation.

neuroscience↗

bioRxiv2021

Reversible inactivation of ferret auditory cortex impairs spatial and non-spatial hearing

A key question in auditory neuroscience is to what extent are brain regions functionally specialized for processing specific sound features such as sound location and identity. In auditory cortex, correlations between neural activity and sounds support both the specialization of distinct cortical subfields, and encoding of multiple sound features within individual cortical areas. However, few studies have tested the contribution of auditory cortex to hearing in multiple contexts. Here we determined the role of ferret primary auditory cortex in both spatial and non-spatial hearing by reversibly inactivating the middle ectosylvian gyrus during behavior using cooling (n=2) or optogenetics (n=1). In optogenetic experiments, we utilized the mDLx promoter to express Channelrhodopsin 2 in GABAergic interneurons and confirmed both viral expression (n=2) and light-driven suppression of spiking activity in auditory cortex, recorded using Neuropixels under anesthesia (n=465 units from 2 additional untrained ferrets). Cortical inactivation impaired vowel discrimination in co-located noise, but not in clean conditions, or when the temporally coincident vowel and noise were spatially separated by 180{degrees}. Testing the ferrets implanted with cooling loops in a sound localization task confirmed that deficits in spatial hearing arose from inactivation of the same region of auditory cortex that was implicated in vowel discrimination in noise. Our results are consistent with single unit recordings in primary auditory cortex showing mixed selectivity for spatial and non-spatial features of sound and suggest a contribution of this region to multiple forms of hearing necessary for auditory scene analysis. Significance StatementNeurons in primary auditory cortex are often sensitive to the location and identity of sounds. Here we inactivated auditory cortex during spatial and non- spatial listening tasks using cooling, or optogenetics. Auditory cortical inactivation impaired multiple behaviors, demonstrating a role in both the analysis of sound location and identity and confirming a functional contribution of mixed selectivity observed in neural activity. Parallel optogenetic experiments in two additional untrained ferrets linked behavior to physiology by demonstrating that expression of Channelrhodopsin 2 permitted rapid light-driven suppression of auditory cortical activity recorded under anesthesia.

neuroscience↗

bioRxiv2021

Sound localization in world and head-centeredspace in ferrets

The location of sounds can be described in multiple coordinate systems that are defined relative to ourselves, or the world around us. Evidence from neural recordings in animals point towards the existence of both head-centered and world-centered representations of sound location in the brain; however, it is unclear whether such neural representations have perceptual correlates in the sound localization abilities of non-human listeners. Here, we establish novel behavioral tests to determine the coordinate systems in which ferrets can localize sounds. We found that ferrets could learn to discriminate between sound locations that were fixed in either world-centered or head-centered space, across wide variations in sound location in the alternative coordinate system. Using probe sounds to assess broader generalization of spatial hearing, we demonstrated that in both head and world-centered tasks, animals used continuous maps of auditory space to guide behavior. Single trial responses of individual animals were sufficiently informative that we could then model sound localization using speaker position in specific coordinate systems and accurately predict ferrets actions in held-out data. Our results indicate that an animal model in which neurons are known to be tuned to sound location in egocentric and allocentric reference frames can also localize sounds in multiple head and world-centered spaces. Significance StatementHumans can describe the location of sounds either relative to themselves, or in the world, independent of their momentary position. These different spaces are also represented in the activity of neurons in animals, but its not clear whether non-human listeners also perceive both head and world-centered sound location. Here, we designed two behavioral tasks in which ferrets had to discriminate between two sounds using their position in the world, or relative to the head. Subjects learnt to solve both problems and showed the ability to generalize sound location in each space when presented with infrequent probe sounds. These findings reveal a perceptual correlate of neural sensitivity previously observed in the ferret brain and establish that, like humans, ferrets can access an auditory map of their local environment.

animal behavior and cognition↗

bioRxiv2021

Hippocampal theta oscillations are modulated by behaviour in the ferret but persist during both locomotion and immobility

Theta oscillations are a hallmark of hippocampal activity across mammals and play a critical role in many hippocampal models of memory and spatial navigation. To reconcile the cross-species differences observed in the presence and properties of theta, we recorded hippocampal local field potentials in rats and ferrets during auditory and visual localisation tasks designed to vary locomotion and sensory attention. Here, we show that theta oscillations occur during locomotion in both ferrets and rats, however during periods of immobility, theta oscillations persisted in the ferret, contrasting starkly with the switch to large irregular activity (LIA) in the rat. Theta during immobility in the ferret was identified as analogous to Type 2 theta that has been observed in rodents due to its sensitivity to atropine, and was modulated by behavioural state, with the strongest theta observed during reward epochs. These results demonstrate that even under similar behavioural conditions, differences exist between species in the relationship between theta and behavioural state.

neuroscience↗

bioRxiv2021

The role of temporal coherence and temporal stability in the build-up of auditory grouping

The cochlea decomposes sounds into separate frequency channels, from which the auditory brain must reconstruct the auditory scene. To do this the auditory system must make decisions about which frequency information should be grouped together, and which should remain distinct. Two key cues for grouping are temporal coherence, resulting from coherent changes in power across frequency, and temporal predictability, resulting from regular or predictable changes over time. To test how these cues contribute to the construction of a sound scene we present listeners with a range of precursor sounds, which act to prime the auditory system by providing information about each sounds structure, followed by a fixed masker in which participants were required to detect the presence of an embedded tone. By manipulating temporal coherence and/or temporal predictability in the precursor we assess how prior sound exposure influences subsequent auditory grouping. In Experiment 1, we measure the contribution of temporal predictability by presenting temporally regular or jittered precursors, and temporal coherence by using either narrow or broadband sounds, demonstrating that both independently contribute to masking/unmasking. In Experiment 2, we measure the relative impact of temporal coherence and temporal predictability and ask whether the influence of each in the precursor signifies an enhancement or disruption of unmasking. We observed that interfering precursors produced the largest changes to thresholds.

neuroscience↗

bioRxiv2020

Seasonal weight changes in laboratory ferrets

Ferrets (Mustela putorius furo) are a valuable animal model used in biomedical research. Ferrets undergo significant variation in body weight seasonally, affected by photoperiod, and these variations make it difficult to use weight as an indicator of health status. To overcome this requires a better understanding of these seasonal weight changes. We provide a normative weight data set for the female ferret accounting for seasonal changes, and also investigate the effect of fluid regulation on weight change. Female ferrets (n=39) underwent behavioural testing from May 2017 to August 2019 and were weighed daily while housed in an animal care facility with controlled light exposure. In the winter (October to March), animals experienced 10 hours of light and 14 hours of dark, while in summer (March to October), this contingency was reversed. Individual animals varied in their body weight from approximately 700 to 1200 g. However, weights fluctuated with light cycle, with animals losing weight in summer, and gaining weight in winter such that they fluctuated between approximately 80% and 120% of their long term average weight. Ferrets were weighed as part of their health assessment while experiencing water regulation for behavioural training. Water regulation superimposed additional weight changes on these seasonal fluctuations, with weight loss during the 5 day water regulation period being greater in summer than winter. These data establish a normative benchmark for seasonal weight variation in female ferrets that can be incorporated into the health assessment of an animals condition.

neuroscience↗

bioRxiv2019

Signal processing in auditory cortex underlies degraded speech sound discrimination in noise

The ability to recognize sounds in noise is a key part of hearing, and the mechanisms by which the brain identifies sounds in noise are of considerable interest to scientists, clinicians and engineers. Yet we know little about the necessity of regions such as auditory cortex for hearing in noise, or how cortical processing of sounds is adversely affected by noise. Here we used reversible cortical inactivation and extracellular electrophysiology in ferrets performing a vowel discrimination task to identify and understand the causal contribution of auditory cortex to hearing in noise. Cortical inactivation by cooling impaired task performance in noisy but not clean conditions, while responses of auditory cortical neurons were less informative about vowel identity in noise. Simulations mimicking cortical inactivation indicated that effects of inactivation were related to the loss of information about sounds represented across neural populations. The addition of noise to target sounds drove spiking activity in auditory cortex and recruitment of additional neural populations that were linked to degraded behavioral performance. To suppress noise-related activity, we used continuous exposure to background noise to adapt the auditory system and recover behavioral performance in both ferrets and humans. Inactivation by cooling revealed that the benefits of continuous exposure were not cortically dependent. Together our results highlight the importance of auditory cortex in sound discrimination in noise and the underlying mechanisms through which noise-related activity and adaptation shape hearing.

neuroscience↗

bioRxiv2018

Training listeners to detect auditory-visual temporal coherence enhances their ability to exploit visual information for auditory scene analysis

The ability to use temporal relationships between cross-modal cues facilitates perception and behavior. Previously we observed that temporally correlated changes in the size of a visual stimulus and the intensity in an auditory stimulus influenced the ability of listeners to perform an auditory selective attention task (Maddox et al., 2015). In this task participants detected timbral changes in a target sound while ignoring those in a simultaneously presented masker. When the visual stimulus was temporally coherent with the target sound, performance was significantly better than when it was temporally coherent with the masker sound, despite the visual stimulus conveying no task-relevant information. Here, we trained observers to detect audiovisual temporal coherence and asked whether this improved their ability to benefit from visual cues during the auditory selective attention task. We observed these listeners improved performance in the auditory selective attention task and changed the way in which they benefited from a visual stimulus: after training performance was better when the visual stimulus was temporally coherent with either the target or the masker stream, relative to the condition in which the visual stimulus was coherent with neither auditory stream. A second group which trained to discriminate modulation rate differences between temporally coherent audiovisual streams improved task performance, but did not change the way in which they used visual information. A control group did not change their performance between pretest and post-test. These results provide insights into how crossmodal experience may optimize multisensory integration.

neuroscience↗

bioRxiv2017

Pitch discrimination performance of ferrets and humans on a go/no-go task.

Animal models are widely used to examine the neurophysiological basis of human pitch perception, and it is therefore important to understand the similarities and differences in pitch processing across species. Pitch discrimination performance is usually measured using two-alternative forced choice (2AFC) procedures in humans and go/no-go tasks in animals, potentially confounding human-to-animal comparisons. We have previously shown that pitch discrimination thresholds of ferrets on a 2AFC task are markedly poorer than those reported for go/no-go tasks in other non-human species (Walker et al., 2009). To better compare the pitch discrimination performance of ferret with other species, here we measure pitch change detection thresholds of ferrets and humans on a common, appetitive go/no-go task design. We found that ferrets pitch thresholds were ~10 times larger than that of humans on the go/no-go task, and were within the range of thresholds reported in other non-human species. Interestingly, ferrets thresholds were 100 times larger than human thresholds on a 2AFC pitch discrimination task using the same stimuli. These results emphasize that sensory discrimination thresholds can differ across tasks, particularly for non-human animals. Performance on our go/no-go task is likely to reflect different neurobiological processes than that on our 2AFC task, as the former required the subjects only to detect a pitch change while the latter required them to label the direction of the pitch change.\n\nABBREVIATIONS\n\nHIGHLIGHTSO_LIPitch discrimination thresholds of ferrets were 10 times larger than those of humans on a go/no-go task\nC_LIO_LIFerrets pitch thresholds are similar to those reported for a range of other mammals\nC_LIO_LIPitch thresholds of ferrets, but not humans, were drastically better on the go/no-go task than a 2AFC task using the same stimuli\nC_LI

animal behavior and cognition↗

bioRxiv2017

Neural correlates of perceptual constancy in Auditory Cortex

Perceptual constancy requires neural representations that are selective for object identity, but also tolerant for identity-preserving transformations. How such representations arise in the brain and contribute to perception remains unclear. Here we studied tolerant representations of sound identity in the auditory system by recording multi-unit activity in tonotopic auditory cortex of ferrets discriminating the identity of vowels which co-varied across orthogonal stimulus dimensions (fundamental frequency, sound level, location and voicing). We found that neural decoding of vowel identity was most successful across the same orthogonal dimensions over which animals generalized their behavior. We also decoded orthogonal sound features and behavioral variables including choice and accuracy to show a behaviorally-relevant, multivariate and multiplexed representation of sound, with each variable represented over a distinct time-course. Finally, information content and timing of sound feature encoding was modulated by task-engagement and training, suggesting that tolerant representations during perceptual constancy are attentionally and experience-dependent.

neuroscience↗

bioRxiv2017

Integration of visual information in auditory cortex promotes auditory scene analysis through multisensory binding

How and where in the brain audio-visual signals are bound to create multimodal objects remains unknown. One hypothesis is that temporal coherence between dynamic multisensory signals provides a mechanism for binding stimulus features across sensory modalities. Here we report that when the luminance of a visual stimulus is temporally coherent with the amplitude fluctuations of one sound in a mixture, the representation of that sound is enhanced in auditory cortex. Critically, this enhancement extends to include both binding and non-binding features of the sound. We demonstrate that visual information conveyed from visual cortex, via the phase of the local field potential, and is combined with auditory information within auditory cortex. These data provide evidence that early cross-sensory binding provides a bottom-up mechanism for the formation of cross-sensory objects and that one role for multisensory binding in auditory cortex is to support auditory scene analysis.

neuroscience↗

bioRxiv2017

Egocentric and Allocentric Representations in Auditory Cortex

A key function of the brain is to provide a stable representation of an objects location in the world. In hearing, sound azimuth and elevation are encoded by neurons throughout the auditory system and auditory cortex is necessary for sound localization. However the coordinate frame in which neurons represent sound space remains undefined: classical spatial receptive fields in head-fixed subjects can be explained either by sensitivity to sound source location relative to the head (egocentric) or relative to the world (allocentric encoding). This coordinate frame ambiguity can be resolved by studying freely moving subjects and here we recorded spatial receptive fields in auditory cortex freely moving ferrets. We found two distinct populations of neurons: While the majority ([~]80%) of spatially tuned neurons represented sound source location relative to the head, we provide novel evidence for a group of neurons in which space was represented in an allocentric world-centered coordinate frame. We also use our ability to measure spatial tuning in moving subjects to explore the influence of sound source distance and speed of head movements on auditory cortical activity and spatial tuning. Modulation depth of spatial tuning increased with distance for egocentric but not allocentric units, whereas for both populations modulation was stronger at faster movement speeds. Our findings argue that auditory cortex is involved in the representation of both sound source location relative to ourselves and sound location in the world independent of our own position.

neuroscience↗