Biology subjects

Holt, L. L.

Publications and source records attributed to Holt, L. L..

12 recordsLinked to original sources

bioRxiv2026

Revisiting the auditory hemodynamic response function in the era of fast fMRI

Recent advances in fast fMRI now enable whole-brain imaging with a TR of [≤]1 s, which has helped to rekindle interest in characterizing the blood oxygen level dependent hemodynamic response function (BOLD HRF). Recent studies in the visual system have found intra-areal differences in temporal response characteristics, as well as HRFs that were faster and narrower than predicted by standard models. The auditory system presents a unique challenge, in that neuronal populations must operate across timescales of microseconds to minutes, and the surface of auditory cortex in particular is intricately and heavily vascularized. Here, we used fast fMRI to characterise voxelwise auditory HRFs evoked by short naturalistic sounds, assessing HRF reproducibility and variability across sessions, participants, and independent datasets. Across two studies at 3 T, participants passively listened to short environmental sounds while fMRI and quantitative MRI data were acquired with a 1s TR. Voxelwise HRFs were estimated via novel cross-session alignment routine, and exclusion of large vascular contributions. We identified a diverse set of hemodynamically plausible response shapes, which were not consistently captured by standard HRF approaches. These responses were reproducible within participants across sessions and robust across two independent acquisitions. Using data-driven gamma models, we achieved stable estimates with relatively few runs, particularly in auditory temporal regions. Within auditory cortex, we observed reproducible spatial gradients in response timing and shape, with faster and higher magnitude responses in medial regions, and slower and lower magnitude responses laterally. Together, these findings demonstrate that auditory HRFs are diverse, reliable, and regionally specific, and highlight the value of fast fMRI and data-driven modelling for advancing interpretation of fMRI data.

neuroscience↗

bioRxiv2025

Independent Basal Ganglia Neural Populations Encode Speech Production and Ambient-Noise Levels

The function of the basal ganglia (BG), a set of nuclei deep in the brain, is still under debate despite their clinical relevance. Lines of evidence from non-human primate and human experiments suggest that one key causal contribution of the adult primate BG is invigoration of movement according to environmental and energetic constraints. Previous studies have come to this conclusion using primarily limb motor control tasks. We hypothesized BG are also important for invigorating the respiratory, vocal, and articulatory motor systems during speech production. To test this, we used a rare clinical opportunity to record local field potentials-broadband gamma activity (LFP-BGA) and single unit (SU) activity from human basal ganglia during deep brain stimulation implant surgeries. Participants repeated sentences aloud in the operating room. We modulated environmental and energetic constraints of speech production by inducing the Lombard Effect, wherein people reliably increase the intensity of their voice in the presence of background noise. Participants increased voice intensity, pitch, vowel space size, and respiratory depth in the presence of ambient noise. [~]40% of LFP and SU sites were modulated by speech production. Comparing globus pallidus (GP) LFP-BGA, herein reported for the first time during speech, to subthalamic nucleus (STN) LFP-BGA revealed GP activated after STN. STN was more coincident with the speech preparatory period and GP more coincident with speech onset, suggesting differential roles in speech production. We found only weak evidence that STN or GP activity encodes the level of produced speech intensity. Instead, we found that LFP-BGA and SU-FR robustly track the ambient background noise levels. Linear decoding from SU-firing rate revealed we could infer the background noise levels with >75% accuracy in any given time point in the trial, including baseline. Importantly, the ambient-noise-modulated sites were an independent population from speech-modulated sites. We conclude that human BG encode the energetic constraints of communication. We theorize that the code is leveraged in downstream BG-cortical loop nodes to invigorate speech oro-motor gestures and co-speech manual limb gestures, both of which respond to ambient noise levels to maintain high-fidelity communication.

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bioRxiv2024

Systematic changes in neural selectivity reflect the acquired salience of category-diagnostic dimensions

Humans and other animals develop remarkable perceptual and cognitive specializations for identifying, differentiating, and acting on classes of ecologically important signals. This expertise is flexible enough to support diverse perceptual judgments: a voice, for example, simultaneously conveys what a talker says, as well as myriad cues about her identity and state. Expert perception across complex signals thus involves discovering and learning regularities that best inform diverse perceptual judgments, as well as weighting this information flexibly as task demands change. Here, we test whether this flexibility may involve endogenous attentional gain. We use two prospective auditory category learning tasks to relate a complex, entirely novel soundscape to four classes of "alien identity" and two classes of "alien size." Identity, but not size, categorization requires discovery and learning of patterned acoustic input situated in one of two simultaneous, non-overlapping frequency bands. This allows us to capitalize on the coarsely segregated frequency-band-specific channels tiling auditory cortex, using fMRI to ask whether category-relevant perceptual information present in one frequency band is prioritized relative to simultaneous, uninformative information in the other frequency band. Among participants expert at alien identity categorization, we observe prioritization of the identity-diagnostic frequency band that persists even when the diagnostic information becomes irrelevant in the size categorization task. Tellingly, the neural selectivity evoked implicitly in the identity categorization task aligns with that in an independent task, where activation is driven by explicit and sustained selective attention to pure tones in one or the other frequency band. Additionally, the learning trajectories taken to achieve expert-level categorization leave fingerprints on the patterns of neural activity associated with the diagnostic dimension. In all, this indicates that acquiring categories can drive the emergence of acquired attentional gain to category-diagnostic input dimensions.

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bioRxiv2024

Distributional learning drives statistical deafening

Humans and other animals use information about how likely it is for something to happen. The absolute and relative probability of an event influences a remarkable breadth of behaviors, from foraging for food to comprehending linguistic constructions -- even when these probabilities are learned implicitly. It is less clear how, and under what circumstances, statistical learning of simple probabilities might drive changes in perception and cognition. Here, across a series of 29 experiments, we probe listeners sensitivity to task-irrelevant changes in the probability distribution of tones acoustic frequency across tone-in-noise detection and tone duration decisions. We observe that the task-irrelevant frequency distribution influences the ability to detect a sound and the speed with which perceptual decisions about its duration are made. The shape of the probability distribution, its range, and a tones relative position within that range impact observed patterns of suppression and enhancement of tone detection and decision making. Perceptual decisions are also modulated by a newly discovered perceptual bias, with lower frequencies in the distribution more often and more rapidly perceived as longer, and higher frequencies as shorter. Perception is sensitive to rapid distribution changes, but distributional learning from previous probability distributions also carries over. In fact, massed exposure to a single point along the dimension results in seemingly maladaptive loss of sensitivity - occurring entirely in the absence of feedback or reward - along a range of subsequently encountered frequencies. This points to a gain mechanism that suppresses sensitivity to regions along a perceptual dimension that are less likely to be encountered. Significance StatementOrganisms as diverse as honeybees and humans pick up on probabilities in the world around them. People implicitly learn the likelihood of a color, price range, or even syntactic structure. How does statistical learning affect how we detect events and make decisions, especially when probabilities are completely irrelevant to the task at hand, and can change without warning? We find that people learn and track changes in perceptual probabilities irrelevant to a task and that this learning drives dynamic shifts in perception characterized by graded effects of enhancement - and primarily - suppression across acoustic frequency. This can result in a remarkably long- lived diminishment of perceptual sensitivity that seems maladaptive but may instead reflect use of likelihood to guide and sharpen perception.

neuroscience↗

bioRxiv2024

A hierarchy of processing complexity and timescales for natural sounds in human auditory cortex

Efficient behavior is supported by humans ability to rapidly recognize acoustically distinct sounds as members of a common category. Within auditory cortex, there are critical unanswered questions regarding the organization and dynamics of sound categorization. Here, we performed intracerebral recordings in the context of epilepsy surgery as 20 patient-participants listened to natural sounds. We built encoding models to predict neural responses using features of these sounds extracted from different layers within a sound-categorization deep neural network (DNN). This approach yielded highly accurate models of neural responses throughout auditory cortex. The complexity of a cortical sites representation (measured by the depth of the DNN layer that produced the best model) was closely related to its anatomical location, with shallow, middle, and deep layers of the DNN associated with core (primary auditory cortex), lateral belt, and parabelt regions, respectively. Smoothly varying gradients of representational complexity also existed within these regions, with complexity increasing along a posteromedial-to-anterolateral direction in core and lateral belt, and along posterior-to-anterior and dorsal-to-ventral dimensions in parabelt. When we estimated the time window over which each recording site integrates information, we found shorter integration windows in core relative to lateral belt and parabelt. Lastly, we found a relationship between the length of the integration window and the complexity of information processing within core (but not lateral belt or parabelt). These findings suggest hierarchies of timescales and processing complexity, and their interrelationship, represent a functional organizational principle of the auditory stream that underlies our perception of complex, abstract auditory information.

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bioRxiv2024

Functional Heterogeneity of Voice-Encoding Cortex Revealed by Clinical Language Mapping

Regions in the superior temporal sulcus and gyrus have been heavily implicated in voice-selective responses in human auditory cortex. Despite an apparent specialization for the encoding of human voice, research outside the auditory domain suggests that these areas likely participate in additional neural processes including speech processing and production. The aim of the current study was to combine results of electrophysiological recording and clinical stimulation mapping procedures in patients undergoing stereoelectroencephalography (sEEG) to explore potential functional heterogeneity in voice-encoding cortex. Both channels that demonstrated voice-encoding properties and channels critically implicated in language functioning were heavily concentrated in the left STG/S. Analysis of functional overlap revealed channels in the posterior STG/S that appear to be involved in both voice encoding and language. Strength of voice encoding in these functionally diverse sites was not significantly different from sites that were implicated in voice encoding alone. Our findings add to prior observations of functional heterogeneity in the STG/S and contribute to proposed models of speech perception. We discuss these results in the context of the utility of electrophysiological methods in mapping cortical networks and identifying regions essential for functioning.

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bioRxiv2024

Intracranial Mapping of Response Latencies and Task Effects for Spoken Syllable Processing in the Human Brain

Prior lesion, noninvasive-imaging, and intracranial-electroencephalography (iEEG) studies have documented hierarchical, parallel, and distributed characteristics of human speech processing. Yet, there have not been direct, intracranial observations of the latency with which regions outside the temporal lobe respond to speech, or how these responses are impacted by task demands. We leveraged human intracranial recordings via stereo-EEG to measure responses from diverse forebrain sites during (i) passive listening to /bi/ and /pi/ syllables, and (ii) active listening requiring /bi/-versus-/pi/ categorization. We find that neural response latency increases from a few tens of ms in Heschls gyrus (HG) to several tens of ms in superior temporal gyrus (STG), superior temporal sulcus (STS), and early parietal areas, and hundreds of ms in later parietal areas, insula, frontal cortex, hippocampus, and amygdala. These data also suggest parallel flow of speech information dorsally and ventrally, from HG to parietal areas and from HG to STG and STS, respectively. Latency data also reveal areas in parietal cortex, frontal cortex, hippocampus, and amygdala that are not responsive to the stimuli during passive listening but are responsive during categorization. Furthermore, multiple regions--spanning auditory, parietal, frontal, and insular cortices, and hippocampus and amygdala--show greater neural response amplitudes during active versus passive listening (a task-related effect). Overall, these results are consistent with hierarchical processing of speech at a macro level and parallel streams of information flow in temporal and parietal regions. These data also reveal regions where the speech code is stimulus-faithful and those that encode task-relevant representations. New & NoteworthyWe leverage direct, intracranial electroencephalography recordings to document speech information flow through diverse sites in the human forebrain, including areas where reported electrode coverage has historically been limited. Our data are consistent with hierarchical processing of speech at a macro level and parallel streams of information flow in temporal and parietal regions. They also reveal regions in the auditory pathway where stimulus-faithful speech codes are transformed to behaviorally relevant representations of speech content.

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bioRxiv2023

Speech induces spatiotemporal and frequency specific subthalamic-cortical spike-phase coupling events

Speech provides a rich context for understanding how cortical interactions with the basal ganglia contribute to unique human behaviors, but opportunities for direct intracranial recordings across cortical-basal ganglia networks are rare. We recorded electrocorticographic signals in the cortex synchronously with single units in the basal ganglia during awake neurosurgeries where subjects spoke syllable repetitions. We discovered that individual STN neurons have transient (200ms) spike-phase coupling (SPC) events with multiple cortical regions. The spike timing of STN neurons was coordinated with the phase of theta-alpha oscillations in the posterior supramarginal and superior temporal gyrus during speech planning and production. Speech sound errors occurred when this STN-cortical interaction was delayed. Our results suggest that the STN supports mechanisms of speech planning and auditory-sensorimotor integration during speech production that are required to achieve high fidelity of the phonological and articulatory representation of the target phoneme. These findings establish a framework for understanding cortical-basal ganglia interaction in other human behaviors, and additionally indicate that firing-rate based models are insufficient for explaining basal ganglia circuit behavior.

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bioRxiv2022

Auditory cortical responses to speech are shaped by statistical learning of short-term speech input regularities

Speech perception presents an exemplary model of how neurobiological systems flexibly adjust when input departs from the norm. Dialects, accents, and even head colds can negatively impact comprehension by shifting speech from listeners expectations. Comprehension improves with exposure to shifted speech regularities, but there is no neurobiological model of this rapid learning. We used electroencephalography to examine human auditory cortical responses to utterances that varied only in fundamental frequency (F0, perceived as voice pitch) as we manipulated the statistical distributions of speech acoustics across listening contexts. Participants overtly categorized speech sampled across two acoustic dimensions that signal /b/ from /p/ (voice onset time [VOT] and F0) to model typical English speech regularities or an expectation-violating accent. These blocks were interleaved with passive exposure to two F0-distinguished test stimuli presented in an oddball ratio to elicit a cortical mismatch negativity (MMN) response. F0 robustly influenced speech categorization when short-term regularities aligned with English but F0 exerted no influence in the context of the accent. The short-term regularities modulated event-related potentials evoked by F0-distinguished test stimuli across both N1 and P3 temporal windows and, for P3 amplitude, there was a strong correlation with perceptual down-weighting of F0. The influence of the short-term regularities persisted to impact MMN in interleaved passive listening blocks when regularities mirrored English but were absent when regularities conveyed the accent. Thus, cortical response is modulated as a function of statistical regularities of the listening context, likely reflecting both early dimension encoding and later categorization. Significance StatementSpeech perception is a quintessential example of how neurobiological systems flexibly adjust when input departs from the norm. Perception is well-tuned to native-language speech patterns. Yet it adjusts when speech diverges from expectations, as with a foreign accent. We observe that the effectiveness of specific cues in speech, like the pitch of a voice, in signaling phonemes like /b/ versus /p/ is dynamically re-weighted when speech violates native-language expectations. We find that this re-weighting is mirrored in cortical responses that reflect both early acoustic dimension encoding and also in later responses linked to phoneme categorization. The results implicate dynamic adjustments in the mapping of speech to cortical representations, as modulated by statistical regularities experienced across local speech input.

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bioRxiv2021

Online tests yield robust thresholds with the right auditory hygiene

Most human auditory psychophysics research has historically been conducted in carefully controlled environments with calibrated audio equipment, and over potentially hours of repetitive testing with expert listeners. Here, we operationally define such conditions as having high auditory hygiene. From this perspective, conducting auditory psychophysical paradigms online presents a serious challenge, in that results may hinge on absolute sound presentation level, reliably estimated perceptual thresholds, low and controlled background noise levels, and sustained motivation and attention. We introduce a set of procedures that address these challenges and facilitate auditory hygiene for online auditory psychophysics. First, we establish a simple means of setting sound presentation levels. Across a set of four level-setting conditions conducted in person, we demonstrate the stability and robustness of this level setting procedure in open air and controlled settings. Second, we test participants tone-in-noise thresholds using widely adopted online experiment platforms and demonstrate that reliable threshold estimates can be derived online in approximately one minute of testing. Third, using these level and threshold setting procedures to establish participant-specific stimulus conditions, we show that an online implementation of the classic probe-signal paradigm can be used to demonstrate frequency-selective attention on an individual-participant basis, using a third of the trials used in recent in-lab experiments. Finally, we show how threshold and attentional measures relate to well-validated assays of online participants in-task motivation, fatigue, and confidence. This demonstrates the promise of online auditory psychophysics for addressing new auditory perception and neuroscience questions quickly, efficiently, and with more diverse samples. Code for the tests is publicly available through Pavlovia and Gorilla.

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bioRxiv2018

Subthalamic nucleus and sensorimotor cortex activity during speech production

The sensorimotor cortex is somatotopically organized to represent the vocal tract articulators, such as lips, tongue, larynx, and jaw. How speech and articulatory features are encoded at the subcortical level, however, remains largely unknown. We analyzed local field potential (LFP) recordings from the subthalamic nucleus (STN) and simultaneous electrocorticography recordings from the sensorimotor cortex of 11 patients (1 female) with Parkinsons disease during implantation of deep brain stimulation (DBS) electrodes, while patients read aloud three-phoneme words. The initial phonemes involved either articulation primarily with the tongue (coronal consonants) or the lips (labial consonants). We observed significant increases in high gamma (60-150 Hz) power in both the STN and the sensorimotor cortex that began before speech onset and persisted for the duration of speech articulation. As expected from previous reports, in the sensorimotor cortex, the primary articulator involved in the production of the initial consonant was topographically represented by high gamma activity. We found that STN high gamma activity also demonstrated specificity for the primary articulator, although no clear topography was observed. In general, subthalamic high gamma activity varied along the ventral-dorsal trajectory of the electrodes, with greater high gamma power recorded in the more dorsal locations of the STN. These results demonstrate that articulator-specific speech information is contained within high gamma activity of the STN, with similar temporal but less specific topographical organization, compared to similar information encoded in the sensorimotor cortex.\n\nSIGNIFICANCE STATEMENTClinical and electrophysiological evidence suggests that the subthalamic nucleus is involved in speech, however, this important basal ganglia node is ignored in current models of speech production. We previously showed that subthalamic nucleus neurons differentially encode early and late aspects of speech production, but no previous studies have examined subthalamic functional organization for speech articulators. Using simultaneous local field potential recordings from the sensorimotor cortex and the subthalamic nucleus in patients with Parkinsons disease undergoing deep brain stimulation surgery, we discovered that subthalamic nucleus high gamma activity tracks speech production at the level of vocal tract articulators, with high gamma power beginning to increase prior to the onset of vocalization, similar to cortical articulatory encoding.

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bioRxiv2017

Subthalamic nucleus neurons differentially encode early and late aspects of speech production

Basal ganglia-thalamocortical loops mediate all motor behavior, yet little detail is known about the role of basal ganglia nuclei in speech production. Using intracranial recording during deep brain stimulation surgery, we tested the hypothesis that the firing rate of subthalamic nucleus neurons is modulated in response to both planning and motor execution aspects of speech. Nearly half of 79 recorded units exhibited firing rate modulation, during a syllable reading task administered in 12 subjects. Trial-to-trial timing of changes in subthalamic neuronal activity, relative to cue onset versus production onset, revealed that locking to cue presentation was associated more with units that decreased firing rate, while locking to speech onset was associated more with units that increased firing rate. These uniquely acquired data indicate that subthalamic activity is dynamic during the production of speech, reflecting temporally-dependent inhibition and excitation of separate populations of subthalamic neurons.

neuroscience↗