Browsing by Author "Groh, Jennifer M"

The inferior colliculus (IC) is an auditory midbrain nucleus essential to the perception of sound frequency and the localization of sound source; yet it remains unclear how the firing rate of primate IC neurons contribute to the localization of concurrent sounds of variable sound frequencies. In this work, I extracellularly recorded the activity of 105 IC neurons while two adult macaque monkeys reported the location(s) of either a single bandpass filtered sound or two concurrent bandpass filtered sounds spatially separated by 24° and separated in sound frequency by 0.25 - 2 octaves. Monkeys performed this task well, with an accuracy of about 80% on single sound trials and about 90% on dual sound trials. The improvement in performance on dual sound trials was not explained by dual sound modulations of IC neural response functions. On dual sound trials, IC neuron receptive fields broadened, and sound frequency accounted for less variance in the dual sound response; and these changes decreased the performance of a maximum-likelihood decoder in correctly labeling the condition of a held out dual sound trial by about 20%. Overall, these results suggest that changes to the IC neural response functions elicited by the presence of a second, concurrent, sound should impair rather than facilitate the IC encoding of concurrent sounds and that an alternative explanation is required to account for monkey performance. I next investigated if recently discovered response alternations, suggested to underlie the encoding of concurrent sounds, were present in the recorded populations. These response alternations occur when an IC neuron alternates its firing rate between the rate corresponding to each component sound of a dual sound pair. These response alternations were observed in about 60% of IC neurons and their contribution to the population response remained stable across the full, 2 octave, range of frequency separations tested. Thus, response alternations are a general mechanism used by the IC to potentially facilitate the encoding of multiple sounds and these results add to a growing body of work observing response alternations across brain areas. The measurements I performed clearly indicate that neurons in the primate IC are sensitive to not only sound frequency and location but also the number of sounds in the environment. Future empirical and theoretical work is needed to elucidate how exactly these response alternations arise and are read out by downstream neurons to allow for the perception of concurrent sounds.

The study of neural phenomena often depends critically on functional maps. Physiologists use topographic organization to identify the location of neural recordings, and in turn to relate activity patterns to underlying anatomy. In this work I investigated the functional architecture of the inferior colliculus (IC) in rhesus monkeys. The IC is an important site of convergence along the mammalian auditory pathway, composed of a number of anatomically and functionally defined regions. I mapped responses to tonal stimuli and acoustic noise in the IC and surrounding tissue using a systematic method, collecting extracellular electrophysiolgical data at evenly placed locations. I found three well organized regions: a central core that showed a topographic organization of sound tuning properties, a surrounding shell that contained neurons tuned to low frequency sounds, and a peripheral area that showed little tuning to frequency. The parcellation of the IC based on tuning properties was confirmed using measures of temporal properties of responses. I then put the map to use, to ask how two non-auditory signals are distributed within the structure. I found that neurons sensitive to eye position are spread throughout the IC, including in the central core region associated with the primary ascending auditory stream. This result has an important implication for models of sensory integration, namely that information from multiple senses meets early, in an area previously thought to be unisensory. Neurons that showed changes in activity directly linked to the presentation of a visual stimulus were less evenly distributed, and only weak responses were found in the core region. Nonetheless, visual sensitivity was not confined to a small subregion of the IC. The results challenge the notion that the senses are combined in nuclei specialized for this purpose.

The environment is sampled by multiple senses, which are woven together to produce a unified perceptual state. However, unifying these senses requires assigning particular signals to the same or different underlying objects or events. Sensory signals originating from the same source should be integrated together, while signals originating from separate sources should be segregated from one another. Each of these computations is associated with different neural encoding strategies, and it is unknown how these strategies interact. Here, we begin to characterize how this problem is solved in the primate brain. First, we developed a behavioral paradigm and applied a computational modeling approach to demonstrate that monkeys, like humans, implement a form of Bayesian causal inference to decide whether two stimuli (one auditory and one visual) originated from the same source. We then recorded single unit neural activity from a representative multisensory brain region, the superior colliculus (SC), while monkeys performed this task. We found that SC neurons encoded either segregated unisensory or integrated multisensory target representations in separate sub-populations of neurons. These responses were well described by a weighted linear combination of unisensory responses which did not account for spatial separation between targets, suggesting that SC sensory responses did not immediately discriminate between common cause and separate cause conditions as predicted by Bayesian causal inference. These responses became less linear as the trial progressed, hinting that such a causal inference may evolve over time. Finally, we implemented a single trial analysis method to determine whether the observed linearity was indicative of true weighted combinations on each trial, or whether this observation was an artifact of pooling data across trials. We found that initial sensory responses (0-150 ms) were well described by linear models even at the single trial level, but that later sustained (150-600 ms) and saccade period responses were instead better described as fluctuating between encoding either the auditory or visual stimulus alone. We also found that these fluctuations were correlated with behavior, suggesting that they may reflect a convergence from the SC encoding all potential targets to preferentially encoding only a specific target on a given trial. Together, these results demonstrate that non-human primates (like humans) perform an idealized version of Bayesian causal inference, that this inference may depend on separate sub-populations of neurons maintaining either integrated or segregated stimulus representations, and that these responses then evolve over time to reflect more complex encoding rules.

Once thought to be predominantly the domain of cortex, multisensory integration has now been found at numerous sub-cortical locations in the auditory pathway. Prominent ascending and descending connection within the pathway suggest that the system may utilize non-auditory activity to help filter incoming sounds as they first enter the ear. Active mechanisms in the periphery, particularly the outer hair cells (OHCs) of the cochlea and middle ear muscles (MEMs), are capable of modulating the sensitivity of other peripheral mechanisms involved in the transduction of sound into the system. Through indirect mechanical coupling of the OHCs and MEMs to the eardrum, motion of these mechanisms can be recorded as acoustic signals in the ear canal. Here, we utilize this recording technique to describe three different experiments that demonstrate novel multisensory interactions occurring at the level of the eardrum. 1) In the first experiment, measurements in humans and monkeys performing a saccadic eye movement task to visual targets indicate that the eardrum oscillates in conjunction with eye movements. The amplitude and phase of the eardrum movement, which we dub the Oscillatory Saccadic Eardrum Associated Response or OSEAR, depended on the direction and horizontal amplitude of the saccade and occurred in the absence of any externally delivered sounds. 2) For the second experiment, we use an audiovisual cueing task to demonstrate a dynamic change to pressure levels in the ear when a sound is expected versus when one is not. Specifically, we observe a drop in frequency power and variability from 0.1 to 4kHz around the time when the sound is expected to occur in contract to a slight increase in power at both lower and higher frequencies. 3) For the third experiment, we show that seeing a speaker say a syllable that is incongruent with the accompanying audio can alter the response patterns of the auditory periphery, particularly during the most relevant moments in the speech stream. These visually influenced changes may contribute to the altered percept of the speech sound. Collectively, we presume that these findings represent the combined effect of OHCs and MEMs acting in tandem in response to various non-auditory signals in order to manipulate the receptive properties of the auditory system. These influences may have a profound, and previously unrecognized, impact on how the auditory system processes sounds from initial sensory transduction all the way to perception and behavior. Moreover, we demonstrate that the entire auditory system is, fundamentally, a multisensory system.

After every eye movement, the brain must realign the visual and auditory reference frames in order to co-locate sights and sounds. Exactly where, when, and how such visual-auditory spatial integrations occur is not fully understood. We recently discovered that the eardrum oscillates beginning a few milliseconds before saccades and continuing until well into ensuing periods of fixation (Gruters et al., 2018)(Gruters, Murphy et al PNAS 2018). Information about at least the horizontal direction and length of saccades appear to be reflected in the phase and magnitude of these eye movement-related eardrum oscillations (EMREO).

Here, we sought to assess the full spatial characteristics of this signal for saccade parameters in both vertical and horizontal dimensions. Concurrently we sought to validate that independent estimations of vertical and horizontal saccade parameter contributions can be linearly combined to predict EMREO waveforms for saccades in all directions – a fundamental assumption of current analyses.

We found that EMREOs depend on both horizontal and vertical saccade components, varying predominantly with eye displacement, but modulated by absolute (initial or final) position as well. In toto, EMREO appear to represent combinations of these saccade parameters such that any saccade corresponds to a specific eardrum oscillation that contains a linear combination of the vertical and horizontal saccade parameters. Regressions in both the time and frequency domain create a fuller picture of the spatial information contained in EMREO. These results demonstrate that detailed information about the relationship between visual and auditory reference frames is present in the earliest stage of the auditory pathway. They also demonstrate that this information is mapped linearly and can therefore be recovered with a small set of basis components.

Future work delving into the relationship between EMREO and the transduction of incoming sounds will be needed to ascertain their effects on the processing of auditory spatial locations in relation to the visual scene. While the frequency and magnitude of EMREO suggest that they may be related to middle ear muscle contractions, the underlying mechanisms that generate them are unknown.

Integrating information from multiple sources is a crucial function of the brain. Examples of such integration include multiple stimuli of different modalties, such as visual and auditory, multiple stimuli of the same modality, such as auditory and auditory, and integrating stimuli from the sensory organs (i.e. ears) with stimuli delivered from brain-machine interfaces.

The overall aim of this body of work is to empirically examine stimulus integration in these three domains to inform our broader understanding of how and when the brain combines information from multiple sources.

First, I examine visually-guided auditory, a problem with implications for the general problem in learning of how the brain determines what lesson to learn (and what lessons not to learn). For example, sound localization is a behavior that is partially learned with the aid of vision. This process requires correctly matching a visual location to that of a sound. This is an intrinsically circular problem when sound location is itself uncertain and the visual scene is rife with possible visual matches. Here, we develop a simple paradigm using visual guidance of sound localization to gain insight into how the brain confronts this type of circularity. We tested two competing hypotheses. 1: The brain guides sound location learning based on the synchrony or simultaneity of auditory-visual stimuli, potentially involving a Hebbian associative mechanism. 2: The brain uses a ‘guess and check’ heuristic in which visual feedback that is obtained after an eye movement to a sound alters future performance, perhaps by recruiting the brain’s reward-related circuitry. We assessed the effects of exposure to visual stimuli spatially mismatched from sounds on performance of an interleaved auditory-only saccade task. We found that when humans and monkeys were provided the visual stimulus asynchronously with the sound but as feedback to an auditory-guided saccade, they shifted their subsequent auditory-only performance toward the direction of the visual cue by 1.3-1.7 degrees, or 22-28% of the original 6 degree visual-auditory mismatch. In contrast when the visual stimulus was presented synchronously with the sound but extinguished too quickly to provide this feedback, there was little change in subsequent auditory-only performance. Our results suggest that the outcome of our own actions is vital to localizing sounds correctly. Contrary to previous expectations, visual calibration of auditory space does not appear to require visual-auditory associations based on synchrony/simultaneity.

My next line of research examines how electrical stimulation of the inferior colliculus influences perception of sounds in a nonhuman primate. The central nucleus of the inferior colliculus is the major ascending relay of auditory information before it reaches the forebrain, and thus an ideal target for understanding low-level information processing prior to the forebrain, as almost all auditory signals pass through the central nucleus of the inferior colliculus before reaching the forebrain. Thus, the inferior colliculus is the ideal structure to examine to understand the format of the inputs into the forebrain and, by extension, the processing of auditory scenes that occurs in the brainstem. Therefore, the inferior colliculus was an attractive target for understanding stimulus integration in the ascending auditory pathway.

Moreover, understanding the relationship between the auditory selectivity of neurons and their contribution to perception is critical to the design of effective auditory brain prosthetics. These prosthetics seek to mimic natural activity patterns to achieve desired perceptual outcomes. We measured the contribution of inferior colliculus (IC) sites to perception using combined recording and electrical stimulation. Monkeys performed a frequency-based discrimination task, reporting whether a probe sound was higher or lower in frequency than a reference sound. Stimulation pulses were paired with the probe sound on 50% of trials (0.5-80 µA, 100-300 Hz, n=172 IC locations in 3 rhesus monkeys). Electrical stimulation tended to bias the animals’ judgments in a fashion that was coarsely but significantly correlated with the best frequency of the stimulation site in comparison to the reference frequency employed in the task. Although there was considerable variability in the effects of stimulation (including impairments in performance and shifts in performance away from the direction predicted based on the site’s response properties), the results indicate that stimulation of the IC can evoke percepts correlated with the frequency tuning properties of the IC. Consistent with the implications of recent human studies, the main avenue for improvement for the auditory midbrain implant suggested by our findings is to increase the number and spatial extent of electrodes, to increase the size of the region that can be electrically activated and provide a greater range of evoked percepts.

My next line of research employs a frequency-tagging approach to examine the extent to which multiple sound sources are combined (or segregated) in the nonhuman primate inferior colliculus. In the single-sound case, most inferior colliculus neurons respond and entrain to sounds in a very broad region of space, and many are entirely spatially insensitive, so it is unknown how the neurons will respond to a situation with more than one sound. I use multiple AM stimuli of different frequencies, which the inferior colliculus represents using a spike timing code. This allows me to measure spike timing in the inferior colliculus to determine which sound source is responsible for neural activity in an auditory scene containing multiple sounds. Using this approach, I find that the same neurons that are tuned to broad regions of space in the single sound condition become dramatically more selective in the dual sound condition, preferentially entraining spikes to stimuli from a smaller region of space. I will examine the possibility that there may be a conceptual linkage between this finding and the finding of receptive field shifts in the visual system.

In chapter 5, I will comment on these findings more generally, compare them to existing theoretical models, and discuss what these results tell us about processing in the central nervous system in a multi-stimulus situation. My results suggest that the brain is flexible in its processing and can adapt its integration schema to fit the available cues and the demands of the task.