Biology subjects

Sen, K.

Publications and source records attributed to Sen, K..

17 recordsLinked to original sources

bioRxiv2026

Parvalbumin and somatostatin interneurons support distinct computations during auditory scene analysis

Auditory scene analysis requires cortical circuits to preserve target-sound representations while suppressing interference from competing sound sources. Although spatial separation between tar{-}get and masker sounds can substantially improve perception, the inhibitory circuit mechanisms that transform spatial separation into improved target sound representations remain poorly un{-}derstood. Here, we used a multi-speaker auditory environment to present target sounds alone (clean) or together with spatially distributed competing white noise (masked) trials while record{-}ing auditory cortical activity in awake mice. By combining electrophysiology, cell-type-specific optogenetic suppression, and spike-distance-based neural classifiers, we examined how parval{-}bumin (PV) and somatostatin (SST) interneurons contribute to spatial processing in complex auditory scenes. PV and SST interneurons made dissociable, context-dependent contributions. PV suppression broadly altered spatial tuning properties, including tuning width, modulation depth, centroid, and sparseness, and reduced target-sound discriminability under clean condi{-}tions. In contrast, SST suppression produced comparatively modest effects on spatial tuning but selectively impaired neural discrimination only during masked trials thereby weakening the im{-}provement in target discrimination normally associated with spatial release from masking. Thus, the interneuron population that most strongly altered spatial tuning was not the population that most strongly disrupted masked discrimination. This reveals a dissociation between cortical in{-}hibitory mechanisms supporting spatial receptive-field structure and those supporting target-masker segregation. Together, these findings suggest that PV-mediated inhibition refines the fi{-}delity of auditory cortical representations, whereas SST-mediated inhibition enhances separation of simultaneously spatially competing sound sources, providing complementary inhibitory mecha{-}nisms for auditory scene analysis.

neuroscience↗

bioRxiv2026

Representations of spatial saliency in auditory cortex are selectively organized through temporal coordination

Selective processing of behaviorally relevant sounds in complex environments requires dynamic modulation of auditory representations. Here, we show that behaviorally relevant sound locations selectively organize auditory cortical activity through temporal coordination rather than changes in firing rate. Using laminar electrophysiology in mice, we recorded activity in primary auditory cortex (A1) activity during a task in which reward was associated with a specific sound location while neutral, non-rewarded sounds were presented across multiple spatial positions. Neurons exhibited increased response reliability, temporal precision, and spike-field coupling to gamma oscillations selectively for sounds presented from behaviorally relevant locations, even when those sounds were unrewarded. These effects were absent during passive listening. Neurons with stronger gamma coupling also had sharper spatial tuning and greater trial-to-trial reliability, linking temporal coordination to representational fidelity. These findings identify gamma-mediated synchronization as a mechanism through which spatial relevance dynamically reshapes auditory encoding.

neuroscience↗

bioRxiv2026

Decoding Spatial Attention in the Cocktail Party Problem Using Wearable Whole-head High-Density fNIRS

Spatial attention is critical for solving the cocktail party problem, a longstanding problem in neuroscience and artificial speech recognition. The ability to decode where humans are attending in a cocktail party like scene would empower applications in brain computer interfaces and assistive devices such as hearing aids. Here we demonstrate that, in an overt attention task, the attended spatial location can be decoded robustly from single trial hemodynamic responses, using a wearable whole head high density fNIRS system. We also identify critical brain regions that make the highest contribution to decoding accuracy. Specifically, we find that decoding based on a small fraction of channels within the left and right inferior parietal lobule (IPL), achieve maximal decoding accuracy comparable to all channels. These results open the way for the design of novel BCIs and assistive devices integrated with fNIRS, that can be steered by spatial attention.

neuroscience↗

bioRxiv2025

A brain-inspired algorithm enhances automatic speech recognitionperformance in multi-talker scenes

Modern automatic speech recognition (ASR) systems are capable of impressive performance recognizing clean speech but struggle in noisy, multi-talker environments, commonly referred to as the "cocktail party problem." In contrast, many human listeners can solve this problem, suggesting the existence of a solution in the brain. Here we present a novel approach that uses a brain inspired sound segregation algorithm (BOSSA) as a preprocessing step for a state-of-the-art ASR system (Whisper). We evaluated BOSSAs impact on ASR accuracy in a spatialized multi-talker scene with one target speaker and two competing maskers, varying the difficulty of the task by changing the target-to-masker ratio. We found that median word error rate improved by up to 54% when the target-to-masker ratio was low. Our results indicate that brain-inspired algorithms have the potential to considerably enhance ASR accuracy in challenging multi-talker scenarios without the need for retraining or fine-tuning existing state-of-the-art ASR systems.

neuroscience↗

bioRxiv2024

Double crossed? Structural and computational studies of an unusual crosslinked heme in Methylococcus capsulatus cytochrome P460

Cytochromes P460 oxidise hydroxylamine within the nitrogen cycle and contain as their active site an unusual catalytic c-type heme where the porphyrin is cross-linked to the protein via a lysine residue in addition to the canonical cross links from cysteine residues. Understanding how enzymes containing P460 heme oxidise hydroxylamine into either nitrous oxide or nitric oxide has implications for climate change. Interestingly the P460 containing hydroxylamine oxidoreductase utilises a tyrosine cross link to heme and performs similar chemistry. Previous crystal structures of cytochrome P460 from Nitrosomonas europaea (NeP460) clearly show the existence of a single crosslink between the Nz atom of lysine and the heme porphyrin with mutagenesis studies indicating roles for the crosslink in positioning a proton transfer residue and/or influencing the distortion of the heme. Here we describe the evidence for a novel double cross link between lysine and heme in the cytochrome P460 from Methylococcus capsulatus (Bath). In order to understand the complexities of this enzyme system we applied high resolution structural biology approaches at synchrotron and XFEL sources paired with crystal spectroscopies. Linked to this we carried out QM/MM simulations that enabled the prediction of electronic absorption spectra providing a crucial validation to linking simulations and experimental structures. Our work demonstrates the feasibility of a double crosslink in McP460 and provides an opportunity to investigate how simulations can interact with experimental structures.

biochemistry↗

bioRxiv2024

A brain-inspired algorithm improves cocktail party listening for individuals with hearing loss

Selective listening in competing-talker situations (restaurants, parties, etc.) is an extraordinarily difficult task for many people. For individuals with hearing loss, this difficulty can be so extreme that it seriously impedes communication and participation in daily life. Directional filtering is one of the only proven ways to improve speech understanding in competition, and most hearing devices now incorporate some kind of directional technology, although real-world benefits are modest, and many approaches fail in competing-talker situations. We recently developed a biologically inspired algorithm that is capable of very narrow spatial tuning and can isolate one talker from a mixture of talkers. The algorithm is based on a hierarchical network model of the auditory system, in which binaural sound inputs drive populations of neurons tuned to specific spatial locations and frequencies, and the spiking responses of neurons in the output layer are reconstructed into audible waveforms. Here we evaluated the algorithm in a group of adults with sensorineural hearing loss, using a challenging competing-talker task. The biologically inspired algorithm led to robust intelligibility gains under conditions in which a standard beamforming approach failed. The results provide compelling support for the potential benefits of biologically inspired algorithms for assisting individuals with hearing loss in "cocktail party" situations.

neuroscience↗

bioRxiv2024

fNIRS Dataset During Complex Scene Analysis

When analyzing complex scenes, humans often focus their attention on an object at a particular spatial location. The ability to decode the attended spatial location would facilitate brain computer interfaces for complex scene analysis (CSA). Here, we investigated capability of functional near-infrared spectroscopy (fNIRS) to decode audio-visual spatial attention in the presence of competing stimuli from multiple locations. We targeted dorsal frontoparietal network including frontal eye field (FEF) and intra-parietal sulcus (IPS) as well as superior temporal gyrus/planum temporal (STG/PT). They all were shown in previous functional magnetic resonance imaging (fMRI) studies to be activated by auditory, visual, or audio-visual spatial tasks. To date, fNIRS has not been applied to decode auditory and visual-spatial attention during CSA, and thus, no such dataset exists yet. This report provides an open-access fNIRS dataset that can be used to develop, test, and compare machine learning algorithms for classifying attended locations based on the fNIRS signals on a single trial basis.

neuroscience↗

bioRxiv2022

A Robust, Compact and Diverse Population Code for Competing Sounds in Auditory Cortex

Cortical circuits encoding sensory information consist of populations of neurons, yet how information aggregates via pooling individual cells remains poorly understood. Such pooling may be particularly important in noisy settings where single neuron encoding is degraded. One example is the cocktail party problem, with competing sounds from multiple spatial locations. How populations of neurons in auditory cortex (ACx) code competing sounds have not been previously investigated. Here, we apply a novel information theoretic approach to estimate information in populations of neurons in ACx about competing sounds from multiple spatial locations, including both summed population (SP) and labeled line (LL) codes. We find that a small subset of neurons is sufficient to nearly maximize mutual information over different spatial configurations, with the LL code outperforming the SP code, and approaching information levels attained without noise. Moreover, with a LL code, units with diverse spatial responses, including both regular and narrow-spiking units, constitute the best pool. Finally, information in the population increases with spatial separation between target and masker, in correspondence with behavioral results on spatial release from masking in human and animals. Taken together, our results reveal that a compact and diverse population of neurons in ACx provide a robust code for competing sounds from different spatial locations.

neuroscience↗

bioRxiv2022

Differential Inhibitory Responses to Temporal Features Enhance Cortical Coding of Dynamic Stimuli: A Network Model

Cortical circuits feature both excitatory and inhibitory cells that underlie the encoding of dynamic sensory stimuli, e.g., speech, music, odors, and natural scenes. While previous studies have shown that inhibition plays an important role in shaping the neural code, how excitatory and inhibitory cells coordinate to enhance encoding of temporally dynamic stimuli is not fully understood. Recent experimental recordings in mouse auditory cortex have shown that optogenetic suppression of parvalbumin neurons results in a decrease of neural discriminability of dynamic stimuli. Here, we present a multilayer model of a cortical circuit that mechanistically explains these results. The model is based on parvalbumin neurons which respond to both stimulus onsets and offsets, as observed experimentally, and incorporates characteristic shortterm synaptic plasticity profiles of excitatory and parvalbumin neurons. We reveal that by tuning the relative strengths of onset and offset inputs to parvalbumin neurons, the model generates different regimes of coding dominated by rapid firing rate modulations or spike timing. Moreover, the model replicates the experimentally observed reduction in neural discrimination performance during optogenetic suppression of parvalbumin neurons. These results suggest that distinct onset and offset inputs to parvalbumin neurons enhance cortical discriminability of dynamic stimuli by encoding distinct temporal features, enhancing temporal coding, and reducing cortical noise. New & NoteworthyHere we propose a model for the mechanisms that underlie neuron responses in the auditory cortex. This study focuses on single channel tuning of simple interactions between neurons. Using physiologically relevant parameters that underly parvalbumin and excitatory neurons, in the proposed artificial network, we show that we can recreate observed results in live studies.

neuroscience↗

bioRxiv2022

Decoding Attended Spatial Location during Complex Scene Analysis with fNIRS.

When analyzing complex scenes, humans often focus their attention on an object at a particular spatial location. The ability to decode the attended spatial location would facilitate brain computer interfaces for complex scene analysis. Here, we investigated functional near-infrared spectroscopys (fNIRS) capability to decode audio-visual spatial attention in the presence of competing stimuli from multiple locations. We targeted dorsal frontoparietal network including frontal eye field (FEF) and intra-parietal sulcus (IPS) as well as superior temporal gyrus/planum temporal (STG/PT). They all were shown in previous functional magnetic resonance imaging (fMRI) studies to be activated by auditory, visual, or audio-visual spatial tasks. We found that fNIRS provides robust decoding of attended spatial locations for most participants and correlates with behavioral performance. Moreover, we found that FEF makes a large contribution to decoding performance. Surprisingly, the performance was significantly above chance level 1s after cue onset, which is well before the peak of the fNIRS response. Our results demonstrate that fNIRS is a promising platform for a compact, wearable technology that could be applied to decode attended spatial location and reveal contributions of specific brain regions during complex scene analysis.

bioengineering↗

bioRxiv2021

PV neurons improve cortical complex scene analysis by enhancing timing-based coding

Cortical representations supporting many cognitive abilities emerge from underlying circuits comprised of several different cell types. However, cell type-specific contributions to rate and timing-based cortical coding are not well-understood. Here, we investigated the role of parvalbumin (PV) neurons in cortical complex scene analysis. Many complex scenes contain sensory stimuli which are highly dynamic in time and compete with stimuli at other spatial locations. PV neurons play a fundamental role in balancing excitation and inhibition in cortex and sculpting cortical temporal dynamics; yet their specific role in encoding complex scenes via timing-based coding, and the robustness of temporal representations to spatial competition, has not been investigated. Here, we address these questions in auditory cortex using a cocktail party-like paradigm, integrating electrophysiology, optogenetic manipulations, and a family of spike-distance metrics, to dissect PV neurons contributions towards rate and timing-based coding. We find that suppressing PV neurons degrades cortical discrimination of dynamic sounds in a cocktail party-like setting via changes in rapid temporal modulations in rate and spike timing, over a wide range of time-scales. Our findings suggest that PV neurons play a critical role in enhancing cortical temporal coding and reducing cortical noise, thereby improving representations of dynamic stimuli in complex scenes. Significance StatementOne impressive example of sensory perception by the brain is its ability to analyze complex scenes, e.g., following what a friend is saying at a party amongst other speakers. Although some humans can solve this problem with relative ease, it remains very difficult for humans with a variety of impairments, e.g., hearing impairments, ADHD, and autism. The brain mechanisms underlying complex scene analysis remain poorly understood. Here, we recorded neural activity in auditory cortex in a complex auditory scene. When we suppressed PV neuron activity in auditory cortex, cortical performance decreased, and the timing of cortical responses was degraded. Our findings suggest that PV neurons improve the brains ability to analyze complex scenes by enhancing the timing of cortical responses while reducing cortical noise.

neuroscience↗

bioRxiv2021

NCoR1 and SMRT fine-tune inflammatory versus tolerogenic balance in dendritic cells by differentially regulating STAT3 signaling

Dendritic cell (DC) fine-tunes inflammatory versus tolerogenic responses to protect from immune-pathology. However, the role of co-regulators in maintaining this balance is unexplored. NCoR1-mediated repression of DC immune-tolerance has been recently reported. Here we found that depletion of NCoR1 paralog SMRT (NCoR2) enhanced cDC1 activation and expression of IL-6, IL-12 and IL-23 while concomitantly decreasing IL-10 expression/secretion. Consequently, co-cultured CD4+ and CD8+ T-cells depicted enhanced Th1/Th17 frequency and cytotoxicity, respectively. Comparative genomic and transcriptomic analysis demonstrated differential regulation of IL-10 by SMRT and NCoR1. SMRT depletion represses mTOR-STAT3-IL10 signaling in cDC1 by downregulating NR4A1. Besides, Nfkbia and Socs3 were down-regulated in Ncor2 (Smrt) knockdown cDC1, supporting increased production of inflammatory cytokines. Moreover, studies in mice showed, adoptive transfer of SMRT knockdown cDC1 in OVA-DTH induced footpad inflammation led to increased Th1/Th17 and reduced tumor burden after B16 melanoma injection by enhancing oncolytic CD8+ T-cell frequency, respectively. We also depicted decreased Ncor2 expression in Rheumatoid Arthritis, a Th1/Th17 disease.

immunology↗

bioRxiv2020

AIM: A Network Model of Attention in Auditory Cortex

Attentional modulation of cortical networks is critical for the cognitive flexibility required to process complex scenes. Current theoretical frameworks for attention are based almost exclusively on studies in visual cortex, where attentional effects are typically modest and excitatory. In contrast, attentional effects in auditory cortex can be large and suppressive. A theoretical framework for explaining attentional effects in auditory cortex is lacking, preventing a broader understanding of cortical mechanisms underlying attention. Here, we present a cortical network model of attention in primary auditory cortex (A1). A key mechanism in our network is attentional inhibitory modulation (AIM) of cortical inhibitory neurons. In this mechanism, top-down inhibitory neurons disinhibit bottom-up cortical circuits, a prominent circuit motif observed in sensory cortex. Our results reveal that the same underlying mechanisms in the AIM network can explain diverse attentional effects on both spatial and frequency tuning in A1. We find that a dominant effect of disinhibition on cortical tuning is suppressive, consistent with experimental observations. Functionally, the AIM network may play a key role in solving the cocktail party problem. We demonstrate how attention can guide the AIM network to monitor an acoustic scene, select a specific target, or switch to a different target, providing flexible outputs for solving the cocktail party problem.

neuroscience↗

bioRxiv2020

A biologically orientated algorithm for spatial sound segregation

Listening in an acoustically cluttered scene remains a difficult task for both machines and hearing-impaired listeners. Normal-hearing listeners accomplish this task with relative ease by segregating the scene into its constituent sound sources, then selecting and attending to a target source. An assistive listening device that mimics the biological mechanisms underlying this behavior may provide an effective solution for those with difficulty listening in acoustically cluttered environments (e.g., a cocktail party). Here, we present a binaural sound segregation algorithm based on a hierarchical network model of the auditory system. In the algorithm, binaural sound inputs first drive populations of neurons tuned to specific spatial locations and frequencies. Lateral inhibition then sharpens the spatial response of the neurons. Finally, the spiking response of neurons in the output layer are then reconstructed into audible waveforms via a novel reconstruction method. We evaluate the performance of the algorithm with psychoacoustic measures of normal-hearing listeners. This two-microphone algorithm is shown to provide listeners with perceptual benefit similar to that of a 16-microphone acoustic beamformer in a difficult listening task. Unlike deep-learning approaches, the proposed algorithm is biologically interpretable and does not need to be trained on large datasets. This study presents a biologically based algorithm for sound source segregation as well as a method to reconstruct highly intelligible audio signals from spiking models. Author SummaryAnimal and humans can navigate complex auditory environments with relative ease, attending to certain sounds while suppressing others. Normally, various sounds originate from various spatial locations. This paper presents an algorithmic model to perform sound segregation based on how animals make use of this spatial information at various stages of the auditory pathway. We showed that the performance of this two-microphone algorithm provides as much benefit to normal-hearing listeners a multi-microphone algorithm. Unlike mathematical and machine-learning approaches, our model is fully interpretable and does not require training with large datasets. Such an approach may benefit the design of machine hearing algorithms. To interpret the spike-trains generated in the model, we designed a method to recover sounds from model spikes with high intelligibility. This method can be applied to spiking neural networks for audio-related applications, or to interpret each node within a spiking model of the auditory cortex.

neuroscience↗

bioRxiv2020

Oscillatory activity in alpha/beta frequencies coordinates auditory and prefrontal cortices during extinction learning

Cortical synchrony is theorized to contribute to communication between connected networks during executive functioning. To understand the functional role of neural synchrony in cognitive flexibility, we recorded from auditory cortex (AC) and medial prefrontal cortex (mPFC), while mice performed an auditory extinction learning task. We found that while animals gradually showed reduced responding to the unrewarded tone over hundreds of trials, the power of local field potential (LFP) oscillations (8-18 Hz, centered at alpha/beta frequencies) in AC and mPFC exhibited immediate and robust increases, prior to behavioral changes. The strength of LFP alpha/beta power in the mPFC, but not AC, was strongly correlated with the behavioral performance that mice would achieve later in the training session. Further, we found that coherence between AC and mPFC at 8-18Hz was selectively enhanced only after mice learned to suppress licking, and this LFP coherence increase coincided with a reduction in spiking rate for the unrewarded tone in AC. These results reveal that enhanced interactions between PFC and AC is an inherent property of auditory discrimination learning, and that coordinated alpha/beta oscillations contribute to cognitive flexibility.

neuroscience↗

bioRxiv2018

Muscarinic receptors regulate auditory and prefrontal cortical communication during auditory processing

Much of our understanding about how acetylcholine modulates prefrontal cortical (PFC) networks comes from behavioral experiments that examine cortical dynamics during highly attentive states. However, much less is known about how PFC is recruited during passive sensory processing and how acetylcholine may regulate connectivity between cortical areas outside of task performance. To investigate the involvement of PFC and cholinergic neuromodulation in passive auditory processing, we performed simultaneous recordings in the auditory cortex (AC) and PFC in awake head fixed mice presented with a white noise auditory stimulus in the presence or absence of local cholinergic antagonists in AC. We found that a subset of PFC neurons were strongly driven by auditory stimuli even when the stimulus had no associative meaning, suggesting PFC monitors stimuli under passive conditions. We also found that cholinergic signaling in AC shapes the strength of auditory driven response in PFC, by modulating the intra-cortical sensory response through muscarinic interactions in AC. Taken together, these findings provide novel evidence that cholinergic mechanisms have a continuous role in cortical gating through muscarinic receptors during passive processing and expand traditional views of prefrontal cortical function and the contributions of cholinergic modulation in sensory gating.\n\nHighlightsO_LIPrefrontal cortex actively monitors non-associative stimuli under passive conditions\nC_LIO_LIAcetylcholine facilitates cortical signaling even outside of attentional contexts\nC_LIO_LILocal scopolamine infusion reduced intracortical signaling and impaired cortical gating\nC_LIO_LImAChR have an ongoing role in sound processing\nC_LI

neuroscience↗

bioRxiv2017

Cooling Induced by Uphill Energy Transport in Plant Photosystems

The uphill energy transfer in photosystems implies input energy at higher wavelength leading to energy output at lower wavelength. Briefly, energy is uphill transported from photosystem I (PSI) to photosystem II (PSII), the latter having a lower wavelength emission. This uphill energy transport involves absorption of thermal energy from the surroundings. While such cooling effects have been reported in laser systems we report for the first time a white light driven cooling in thylakoid suspension. The cooling of the surrounding medium by appropriate illumination was illustrated using thermal measurements. Again cooling is inhibited by agents like 3-(3,4-Dichlorophenyl)-1,1-dimethylurea,that block the linear electron flow between the photocenters, implying a dependence of the cooling on interplay between such centers. Furthermore, it is possible to modulate the cooling pattern by addition of external agents like nanopaticles, some favoring further cooling (e.g., Ag nanoparticle) and some like Au or chlorophyll nanoparticles, showing insignificant or even reverse trends. Interestingly, the cooling is invariably associated with the 77K spectra of the thylakoid suspension. With reference to the dark control, an agent causing cooling always increases PSII to PSI ratio and vice versa i.e.,the uphill energy transport. Importantly, the cooling effect, apart from its import role in plant physiology can be exploited artificially for energy saving in post-harvest or food preservation.

bioengineering↗