Biology subjects

Schroeder, C. E.

Publications and source records attributed to Schroeder, C. E..

At least 19 recordsLinked to original sources

bioRxiv2026

Biophysical modeling reveals how recording geometry shapes representations of cortical activity

Extracellular electrophysiological recordings reflect both the organization of neural activity and the geometry through which that activity is sampled. Here, we used biophysical modeling and experimental recordings from the macaque auditory cortex to determine how cortical activity is transformed across neural sources, extracellular signals, and recording geometries. In a biophysically detailed thalamocortical model, four separately instantiated cortical-column conditions spanning graded thalamic recruitment exhibited a graded response hierarchy across local field potential, current-source density, and multiunit activity, despite signal-dependent differences in the contributions of cortical neuronal populations. We then arranged independently simulated cortical columns into controlled spatial configurations and sampled the same underlying sources using virtual linear laminar and Directional and Scalable (DiSc) electrode arrays. The linear geometry primarily represented variation along cortical depth, whereas DiSc additionally represented circumferential variation associated with lateral source organization, demonstrating that recording geometry determines which spatial dimensions of common underlying activity are represented in extracellular measurements. Experimental recordings obtained with the corresponding geometries were consistent with these model-derived predictions: broadband-noise responses exhibited spatial organization shared across tone-evoked responses in both multidimensional DiSc maps and laminar profiles, despite substantial variation in frequency-dependent response magnitude across penetrations. Together, these results show that extracellular measurements represent an interaction between biological source organization and recording geometry. Biophysical forward modeling therefore provides a framework for determining which features of underlying circuit organization remain identifiable after extracellular sampling and for relating neural-interface design to the dimensions of cortical activity accessible experimentally.

neuroscience↗

bioRxiv2026

Spectrotemporal signatures of driving and modulatory circuits across cortical and subcortical networks

Sensory processing depends on interactions between neural circuits that convey and regulate information across cortical and subcortical networks. Classical frameworks distinguish driving inputs, which transmit sensory content via suprathreshold activation, from modulatory inputs, which alter neuronal excitability without directly eliciting spiking. However, physiological signatures of these circuit types that generalize widely across distributed brain regions remain unclear. Here, we functionally differentiate driving and modulatory circuits in the awake macaque brain by jointly quantifying suprathreshold multiunit activity (MUA) and oscillatory phase coherence (inter-trial coherence, ITC) across eight cortical and thalamic structures during auditory, visual, and motor sampling conditions. Preferred sensory stimuli elicited broadband ITC increases accompanied by robust MUA, yielding relatively uniform spectral distributions across adjacent frequency bands, consistent with driving inputs. In contrast, non-preferred sensory and motor-related events produced narrowband, frequency-specific ITC modulation without concurrent firing, and was characterized by dominant peaks at stimulation or event rates, which is consistent with modulatory inputs. This narrowband ITC modulation is indicative of coordinated phase alignment, capable of dynamically regulating information transfer, mediated by driving inputs, across thalamocortical circuits. These response types were observed within individual regions, revealing two separable modes of neural activity. These findings identify distinct spectrotemporal signatures of driving and modulatory activity and demonstrate that subthreshold oscillatory modulation is a widespread mechanism for coordinating multisensory and motor influences on perception.

neuroscience↗

bioRxiv2026

Dose-dependent power and connectivity modulation of low frequency oscillations through transcranial magnetic stimulation in non-human primates.

Transcranial magnetic stimulation (TMS) is a powerful non-invasive tool for safely modulating neural activity in humans. In particular, the left dorsolateral prefrontal cortex (DLPFC) is a common target site for clinical interventions in disorders such as treatment-resistant depression. Yet, clinical trials investigating the efficacy of TMS often lack neural markers of target engagement of the DLPFC. Local field potentials (LFPs), such as prefrontal theta oscillations, have been implicated in the clinical symptoms of these disorders. However, non-invasive electroencephalography (EEG) recordings in humans are limited by their spatial resolution and challenges of interpreting EEG signals. In this study, we investigate the effects of single-pulse TMS applied to the left prefrontal cortex in non-human primates on LFPs recorded through intracranial EEG. Compared to sham TMS, the intensity of active TMS pulses scaled with LFP power changes in a 1-13 Hz range at contacts close to the stimulation site in the prefrontal cortex (e.g., caudate nucleus, anterior cingulate cortex, insular cortex) as well as contacts that were more distal (e.g., posterior cingulate cortex, temporal lobe). To test how TMS modulates connectivity between these regions, we conducted a phase-based connectivity analysis. TMS pulses initially enhanced and then disrupted connectivity at 1-13 Hz between the stimulation site and other contacts. Connectivity rebounded approximately 1500 ms post-stimulation. Only the initial enhancement in connectivity scaled with TMS intensity. Our results demonstrate a dose-dependent power modulation of low frequency LFPs across prefrontal, parietal and temporal cortical regions by single pulses. Furthermore, they show that TMS applied over the left prefrontal cortex can enhance and interrupt short- and long-range connectivity. Our study advances the understanding of the effects of TMS on brain oscillations and connectivity with direct relevance for clinical applications in neuromodulation therapies.

neuroscience↗

bioRxiv2024

Eye movements organize excitability state, information coding and network connectivity in the human hippocampus

Natural vision is an active sensing process that entails frequent eye movements to sample the environment. Nonetheless vision is often studied using passive viewing with eye position held constant. Using closed-loop eye-tracking, with saccade-contingent stimulation and simultaneous intracranial recordings in surgical epilepsy patients, we tested the critical role of eye movement signals during natural visual processing in the hippocampus and hippocampal-amygdala circuit. Prior work shows that saccades elicit phase reset of ongoing neural excitability fluctuations across a broad array of cortical and subcortical areas. Here we show that saccade-related reset systematically modulates neuronal ensemble responses to visual input, enables phase-coding of information across the saccade-fixation cycle and modulates network connectivity between hippocampus and amygdala. The saccade-fixation cycle thus emerges as a fundamental sampling unit, organizing a range of neural operations including input representation, network connectivity and information coding. One-Sentence SummarySaccade-fixation cycle: a fundamental sampling unit, organizing input representation, information coding and network activation

neuroscience↗

bioRxiv2024

Layer-specific dynamics of local field potentials in monkey V1 during electrical stimulation

The mammalian neocortex, organized into six cellular layers or laminae, forms a cortical network within layers. Layer specific computations are crucial for sensory processing of visual stimuli within primary visual cortex. Laminar recordings of local field potentials (LFPs) are a powerful tool to study neural activity within cortical layers. Electric brain stimulation is widely used in basic neuroscience and in a large range of clinical applications. However, the layer-specific effects of electric stimulation on LFPs remain unclear. To address this gap, we conducted laminar LFP recordings of the primary visual cortex in monkeys while presenting a flash visual stimulus. Simultaneously, we applied a low frequency sinusoidal current to the occipital lobe with offset frequency to the flash stimulus repetition rate. We analyzed the modulation of visual-evoked potentials with respect to the applied phase of the electric stimulation. Our results reveal that only the deeper layers, but not the superficial layers, show phase-dependent changes in LFP components with respect to the applied current. Employing a cortical column model, we demonstrate that these in vivo observations can be explained by phase-dependent changes in the driving force within neurons of deeper layers. Our findings offer crucial insight into the selective modulation of cortical layers through electric stimulation, thus advancing approaches for more targeted neuromodulation.

biophysics↗

bioRxiv2024

Is there a ubiquitous spectrolaminar motif of local field potential power across primate neocortex?

Mendoza-Halliday, Major et al.1 (referred to as "Mendoza-Halliday et al." for brevity), advocate for a local field potential (LFP)-based approach to functional identification of cortical layers during "laminar" (simultaneous recordings from all cortical layers) multielectrode recordings in nonhuman primates (NHPs). They describe a "ubiquitous spectrolaminar motif" in the primate neocortex: 1) 75-150 Hz power peaks in the supragranular layers, 2) 10-19 Hz power peaks in the infragranular layers and 3) the crossing point of their laminar power gradients identifies Layer 4 (L4). Identification of L4 is critical in general, but especially for Mendoza-Halliday et al. as the "motif" discovery is couched within a framework whose central hypothesis is that gamma activity originates in the supragranular layers and reflects feedforward activity, while alpha-beta activity originates in the infragranular layers and reflects feedback activity. In an impressive scientific effort, Mendoza-Halliday et al. analyzed laminar data from 14 cortical areas in 2 prior macaque studies and compared them to marmoset, mouse, and human data to further bolster the canonical nature of the motif. Identification of such canonical principles of brain operation is clearly a topic of broad scientific interest. Similarly, a reliable online method for L4 identification would be of broad scientific value for the rapidly increasing use of laminar recordings using numerous evolving technologies. Despite Mendoza-Halliday et al.s papers strengths, and its potential for scientific impact, a series of concerns that are fundamental to the analysis and interpretation of laminar activity profile data in general, and local field potential (LFP) signals in particular, led us to question its conclusions. Here, we address four key questions: Q1) Is the spectrolaminar motif ubiquitous, i.e. "found everywhere" or "universal"? Q2) Do features of the motif reliably identify Layer (L) 4? Q3) Are Mendoza-Halliday et al.s newly introduced methods (FLIP and vFLIP) reliable? And Q4) Are the proposed biophysical mechanisms underlying the motif well justified? We used new sets of data comprised of stimulus-evoked laminar response profiles from primary and higher-order auditory cortices (A1 and belt cortex), and primary visual cortex (V1) to test these questions. The rationale for using these areas as a test bed for new methods is that, in contrast to higher-order cortical areas, their laminar anatomy and physiology have already been extensively characterized by prior studies, and there is general agreement across laboratories on key matters like L4 identification. In short, we find that Mendoza-Halliday et al.s findings do not generalize well to these cortical areas. Specifically, regarding Q1: Though we can find a spectrolaminar gradient that is qualitatively consistent with Mendoza-Halliday et al., it is quantifiable in only 61-64% of our recordings, indicating that the motif is common but by no means universal (see "Evaluation of the FLIP method [...]" and "Evaluation of vFLIP [...]"). Regarding Q2: The motifs high/low frequency gradient cross point identified L4 in only 29-33% of our recordings. Regarding Q3: FLIP and vFLIP exhibit marked variability across studies, across brain areas, and spuriously detect cortical layer inversions (see "FLIPs fitting process [...]" and "Evaluation of vFLIP [...]"). Regarding Q4: the biophysical modeling findings cited to support Mendoza-Hallidays conclusions (see "Going forward - in silico [...]") do not reproduce the LFP data trends. While our findings are in many respects at odds with those of Mendoza-Halliday et al., the paper already has, and will continue to spark debate and further experimentation. Hopefully this countervailing presentation will lead to robust collegial efforts to define optimal strategies for applying laminar recording methods in future studies.

neuroscience↗

bioRxiv2023

Experimental validation of computational models for the prediction of phase distribution during multi-channel transcranial alternating current stimulation

Transcranial alternating current stimulation (tACS) is a widely used noninvasive brain stimulation (NIBS) technique to affect neural activity. Neural oscillations exhibit phase-dependent associations with cognitive functions, and tools to manipulate local oscillatory phases can affect communication across remote brain regions. A recent study demonstrated that multi-channel tACS can generate electric fields with a phase gradient or traveling waves in the brain. Computational simulations using phasor algebra can predict the phase distribution inside the brain and aid in informing parameters in tACS experiments. However, experimental validation of computational models for multi-phase tACS is still lacking. Here, we develop such a framework for phasor simulation and evaluate its accuracy using in vivo recordings in nonhuman primates. We extract the phase and amplitude of electric fields from intracranial recordings in two monkeys during multi-channel tACS and compare them to those calculated by phasor analysis using finite element models. Our findings demonstrate that simulated phases correspond well to measured phases (r = 0.9). Further, we systematically evaluated the impact of accurate electrode placement on modeling and data agreement. Finally, our framework can predict the amplitude distribution in measurements given calibrated tissues conductivity. Our validated general framework for simulating multi-phase, multi-electrode tACS provides a streamlined tool for principled planning of multi-channel tACS experiments.

bioengineering↗

bioRxiv2022

Mesoscale neural effects of transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method that is rapidly growing in popularity for studying causal brain-behavior relationships. However, its dose-dependent direct neural mechanisms, i.e., due to electric field or connectivity, and peripheral sensory co-stimulation effects remain debated. Understanding how TMS stimulation parameters affect brain responses is vital for the rational design of TMS protocols. Studying these mechanisms in humans is challenging due to the limited spatiotemporal resolution of available non-invasive neuroimaging methods. Here, we leverage invasive recordings of local field potentials in non-human primates to study TMS mesoscale responses. We demonstrate that early TMS-evoked potentials show a sigmoidal dose-response with stimulation intensity. We further show that stimulation responses are spatially specific. We employ several control conditions to dissociate direct neural responses from auditory and somatosensory co-activation. These results provide crucial evidence regarding TMS neural effects at the brain circuit level. Our findings are highly relevant for interpreting human TMS studies and biomarker developments for TMS target engagement in clinical applications.

neuroscience↗

bioRxiv2022

Semantic novelty modulates neural responses to visual change across the human brain

Our continuous visual experience in daily life is dominated by change. Previous research has focused on visual change due to stimulus motion, eye movements or unfolding events, but not their combined impact across the brain, or their interactions with semantic novelty. We investigate the neural responses to these sources of novelty during film viewing. We analyzed intracranial recordings in humans across 6328 electrodes from 23 individuals. Responses associated with saccades and film cuts were dominant across the entire brain. Film cuts at semantic event boundaries were particularly effective in the temporal and medial temporal lobe. Saccades to visual targets with high visual novelty were also associated with strong neural responses. Specific locations in higher-order association areas showed selectivity to either high or low-novelty saccades. We conclude that neural activity associated with film cuts and eye movements is widespread across the brain and is modulated by semantic novelty.

neuroscience↗

bioRxiv2022

Saccadic modulation of neural excitability in auditory areas of the neocortex

SummaryIn natural "active" vision, humans and other primates use eye movements (saccades) to sample bits of information from visual scenes. In this process, nonretinal signals linked to saccades shift visual cortical neurons to a high excitability state as each saccade ends. The extent of this saccadic modulation outside of the visual system is unknown. Here, we show that during natural viewing, saccades modulate excitability in numerous auditory cortical areas, with a pattern complementary to that seen in visual areas. Bi-directional functional connectivity patterns suggest that these effects may arise from regions involved in saccade generation. By using saccadic signals to yoke excitability states in auditory areas to those in visual areas, the brain can improve information processing in complex natural settings.

neuroscience↗

bioRxiv2022

Saccade-related modulation of oscillatory activity in primary auditory cortex

The auditory and visual sensory systems are both used by the brain to obtain and organize information from our external environment, yet there are fundamental differences between these two systems. Visual information is acquired using systematic patterns of fixations and saccades, which are controlled by internal motor commands. Sensory input occurs in volleys that are tied to the timing of saccades. In contrast, the auditory system does not use such an overt motor sampling routine so the relationship between sensory input timing and motor activity is less clear. Previous studies of primary visual cortex (V1) in nonhuman primates (NHP) have shown that there is a cyclical modulation of excitability tied to the eye movement cycle and suggests that this excitability modulation stems from the phase reset of neuronal oscillations. We hypothesized that if saccades provide a supramodal temporal context for environmental information then we should also see saccade-related modulation of oscillatory activity in primary auditory cortex (A1) as NHPs shift their gaze around their surroundings. We used linear array multielectrodes to record cortical laminar neuroelectric activity profiles while subjects sat in a dark or dimly lit and silent chamber. Analysis of oscillatory activity in A1 suggests that saccades lead to a phase reset of neuronal oscillations in A1. Saccade-related phase reset of delta oscillations were observed across all layers while theta effects occurred primarily in extragranular layers. Although less frequent, alpha oscillations also showed saccade-related phase reset within the extragranular layers. Our results confirm that saccades provide a supramodal temporal context for the influx of sensory information into A1 and highlight the importance of considering the effects of eye position on auditory processing. Significance StatementUsing laminar multielectrodes, the current study examined saccade-related neuronal activity during resting state while NHPs sat in a dark or dimly lit room. Our results confirm that saccade-related modulation of delta band oscillatory activity occurs across all layers of A1. Interestingly, our data also show a saccade-related phase reset of theta and alpha bands that preferentially occurs in extragranular layers. These results confirm that saccades provide a supramodal temporal context for the influx of environmental information into A1 and emphasizes the importance of considering eye position when examining auditory processing.

neuroscience↗

bioRxiv2022

Data-driven multiscale model of macaque auditory thalamocortical circuits reproduces in vivo dynamics

We developed a biophysically-detailed model of the macaque auditory thalamocortical circuits, including primary auditory cortex (A1), medial geniculate body (MGB) and thalamic reticular nuclei (TRN), using the NEURON simulator and NetPyNE multiscale modeling tool. We simulated A1 as a cortical column with a depth of 2000 m and 200 m diameter, containing over 12k neurons and 30M synapses. Neuron densities, laminar locations, classes, morphology and biophysics, and connectivity at the long-range, local and dendritic scale were derived from published experimental data. The A1 model included 6 cortical layers and multiple populations of neurons consisting of 4 excitatory and 4 inhibitory types, and was reciprocally connected to the thalamus (MGB and TRN), mimicking anatomical connectivity. MGB included core and matrix thalamocortical neurons with layer-specific projection patterns to A1, and thalamic interneurons projecting locally. Auditory stimulus-related inputs to the MGB were simulated using phenomenological models of the cochlear/auditory nerve and the inferior colliculus. The model generated cell type and layer-specific firing rates consistent with experimentally observed ranges, and accurately simulated the corresponding local field potentials (LFPs), current source density (CSD), and electroencephalogram (EEG) signals. Laminar CSD patterns during spontaneous activity, and in response to speech input, were similar to those recorded experimentally. Physiological oscillations emerged spontaneously across frequency bands without external rhythmic inputs and were comparable to those recorded in vivo. We used the model to unravel the contributions from distinct cell type and layer-specific neuronal populations to oscillation events detected in CSD, and explored how these relate to the population firing patterns. Overall, the computational model provides a quantitative theoretical framework to integrate and interpret a wide range of experimental data in auditory circuits. It also constitutes a powerful tool to evaluate hypotheses and make predictions about the cellular and network mechanisms underlying common experimental measurements, including MUA, LFP and EEG signals.

neuroscience↗

bioRxiv2021

Spontaneous neural oscillations influence behavior and sensory representations by suppressing neuronal excitability

The ability to process and respond to external input is critical for adaptive behavior. Why, then, do neural and behavioral responses vary across repeated presentations of the same sensory input? Spontaneous fluctuations of neuronal excitability are currently hypothesized to underlie the trial-by-trial variability in sensory processing. To test this, we capitalized on invasive electrophysiology in neurosurgical patients performing an auditory discrimination task with visual cues: specifically, we examined the interaction between prestimulus alpha oscillations, excitability, task performance, and decoded neural stimulus representations. We found that strong prestimulus oscillations in the alpha+ band (i.e., alpha and neighboring frequencies), rather than the aperiodic signal, correlated with a low excitability state, indexed by reduced broadband high-frequency activity. This state was related to slower reaction times and reduced neural stimulus encoding strength. We propose that the alpha+ rhythm modulates excitability, thereby resulting in variability in behavior and sensory representations despite identical input.

neuroscience↗

bioRxiv2020

U-Net Model for Brain Extraction on Non-human Primates

Brain extraction (a.k.a. skull stripping) is a fundamental step in the neuroimaging pipeline as it can affect the accuracy of downstream preprocess such as image registration, tissue classification, etc. Most brain extraction tools have been designed for and applied to human data and are often challenged by non-human primates (NHP) data. Amongst recent attempts to improve performance on NHP data, deep learning models appear to outperform the traditional tools. However, given the minimal sample size of most NHP studies and notable variations in data quality, the deep learning models are very rarely applied to multi-site samples in NHP imaging. To overcome this challenge, we used a transfer-learning framework that leverages a large human imaging dataset to pretrain a convolutional neural network (i.e. U-Net Model), and then transferred this to NHP data using a small NHP training sample. The resulting transfer-learning model converged faster and achieved more accurate performance than a similar U-Net Model trained exclusively on NHP samples. We improved the generalizability of the model by upgrading the transfer-learned model using additional training datasets from multiple research sites in the Primate Data-Exchange (PRIME-DE) consortium. Our final model outperformed brain extraction routines from popular MRI packages (AFNI, FSL, and FreeSurfer) across a heterogeneous sample from multiple sites in the PRIME-DE with less computational cost (20s~10min). We also demonstrated the transfer-learning process enables the macaque model to be updated for use with scans from chimpanzees, marmosets, and other mammals (e.g. pig). Our model, code, and the skull-stripped mask repository of 136 macaque monkeys are publicly available for unrestricted use by the neuroimaging community at https://github.com/HumanBrainED/NHP-BrainExtraction.

neuroscience↗

bioRxiv2020

Does the phase of ongoing EEG oscillations predict auditory perception?

Effective processing of information from the environment requires the brain to selectively sample relevant inputs. The visual perceptual system has been shown to sample information rhythmically, oscillating rapidly between more and less input-favorable states. Evidence of parallel effects in auditory perception is inconclusive. Here, we combined a bilateral pitch-identification task with electroencephalography (EEG) to investigate whether the phase of ongoing EEG predicts auditory discrimination accuracy. We compared prestimulus phase distributions between correct and incorrect trials. Shortly before stimulus onset, each of these distributions showed significant phase concentration, but centered at different phase angles. The effects were strongest in theta and beta frequency bands. The divergence between phase distributions showed a linear relation with accuracy, accounting for at least 10% of inter-individual variance. Discrimination performance oscillated rhythmically at a rate predicted by the neural data. These findings indicate that auditory discrimination threshold oscillates over time along with the phase of ongoing EEG activity. Thus, it appears that auditory perception is discrete rather than continuous, with the phase of ongoing EEG oscillations shaping auditory perception by providing a temporal reference frame for information processing.

neuroscience↗

bioRxiv2020

The role of motor and environmental visual rhythms in structuring auditory cortical excitability

One of the ways we perceive our external world is through the process of active sensing in which biological sensors (e.g. fingers and eyes) sample the environment utilizing mostly rhythmic motor routines. Previous studies indicate that these motor sampling patterns modulate neuronal excitability in sensory brain regions by entraining brain rhythms, a process termed motor-initiated entrainment. Additionally, rhythms of the external environment, that are independent of internal motor commands, are also capable of entraining rhythmic brain activity. The goal of our study was twofold. First, we aimed to investigate the properties of motor-initiated entrainment in the auditory system using the most prominent motor sampling pattern in primates, eye movements. Second, we wanted to determine whether/how motor-initiated entrainment by eye movements interacts with visual environmental entrainment. By examining laminar profiles of neuronal ensemble activity in the primary auditory cortex of non-human primates, we found that while motor-initiated entrainment has a suppressive, visual environmental entrainment has an enhancive effect. We also found that the two processes are temporally coupled during free viewing, and their temporal relationship ensures that their effect on neuronal ensemble excitability is complementary rather than interfering. Taken together, our results provide strong evidence that motor and sensory systems continuously interact in orchestrating the brains rhythmic context for the optimal sampling of our multisensory environment.

neuroscience↗

bioRxiv2020

Saccadic modulation of neural activity in the human anterior thalamus during visual active sensing

Humans and other primates explore visual scenes by active sensing, using saccadic eye movements to relocate the fovea and sample different bits of information multiple times per second. Saccades induce a phase reset of ongoing neuronal oscillations in primary and higher-order visual cortices and medial temporal lobe. As a result, neuron ensembles are shifted to a common state at the time visual input propagates through the system (i.e., just after fixation). The extent of the brains circuitry modulated by saccades is not yet known. Here, we evaluate the possibility that saccadic phase reset impacts the anterior nuclei of the thalamus (ANT). Using rare recordings in the human thalamus of three surgical patients, we found saccade-related phase concentration, peaking at 3-4 Hz, coincident with suppression of Broadband High-frequency Activity (BHA; 80-180 Hz). Our results provide evidence for saccade-related modulation of neuronal excitability dynamics in the ANT, consistent with the idea that these nuclei are engaged during visual active sensing. These findings show that during real-world active visual exploration neural dynamics in the human ANT, a part of extended hippocampal-diencephalic system for episodic memory, exhibit modulations that might be underestimated in typical passive viewing.

neuroscience↗

bioRxiv2020

Differential contributions of synaptic and intrinsic inhibitory currents to parsing via flexible phase-locking in neural oscillators

Current hypotheses suggest that speech segmentation - the initial division and grouping of the speech stream into candidate phrases, syllables, and phonemes for further linguistic processing - is executed by a hierarchy of oscillators in auditory cortex. Theta (~3-12 Hz) rhythms play a key role by phase-locking to recurring acoustic features marking syllable boundaries. Reliable synchronization to quasi-rhythmic inputs, whose variable frequency can dip below cortical theta frequencies (down to ~1 Hz), requires "flexible" theta oscillators whose underlying neuronal mechanisms remain unknown. Using biophysical computational models, we found that the flexibility of phase-locking in neural oscillators depended on the types of hyperpolarizing currents that paced them. Simulated cortical theta oscillators flexibly phase-locked to slow inputs when these inputs caused both (i) spiking and (ii) the subsequent buildup of outward current sufficient to delay further spiking until the next input. The greatest flexibility in phase-locking arose from a synergistic interaction between intrinsic currents that was not replicated by synaptic currents at similar timescales. Flexibility in phase-locking enabled improved entrainment to speech input, optimal at mid-vocalic channels, which in turn supported syllabic-timescale segmentation through identification of vocalic nuclei. Our results suggest that synaptic and intrinsic inhibition contribute to frequency-restricted and -flexible phase-locking in neural oscillators, respectively. Their differential deployment may enable neural oscillators to play diverse roles, from reliable internal clocking to adaptive segmentation of quasi-regular sensory inputs like speech. Author summaryOscillatory activity in auditory cortex is believed to play an important role in auditory and speech processing. One suggested function of these rhythms is to divide the speech stream into candidate phonemes, syllables, words, and phrases, to be matched with learned linguistic templates. This requires brain rhythms to flexibly synchronize with regular acoustic features of the speech stream. How neuronal circuits implement this task remains unknown. In this study, we explored the contribution of inhibitory currents to flexible phase-locking in neuronal theta oscillators, believed to perform initial syllabic segmentation. We found that a combination of specific intrinsic inhibitory currents at multiple timescales, present in a large class of cortical neurons, enabled exceptionally flexible phase-locking, which could be used to precisely segment speech by identifying vowels at mid-syllable. This suggests that the cells exhibiting these currents are a key component in the brains auditory and speech processing architecture.

neuroscience↗