Biology subjects

Self, M. W.

Publications and source records attributed to Self, M. W..

12 recordsLinked to original sources

bioRxiv2024

Pronouns reactivate conceptual representations in human hippocampal neurons

During discourse comprehension, every new word adds to an evolving representation of meaning that accumulates over consecutive sentences and constrains the next words. To minimize repetition and utterance length, languages use pronouns, like the word she, to refer to nouns and phrases that were previously introduced. It has been suggested that language comprehension requires that pronouns activate the same neuronal representations as the nouns themselves. Here, we test this hypothesis by recording from individual neurons in the human hippocampus during a reading task. We found that cells that are selective to a particular noun are later reactivated by pronouns that refer to the cells preferred noun. These results imply that concept cells contribute to a rapid and dynamic semantic memory network which is recruited during language comprehension. This study uniquely demonstrates, at the single-cell level, how memory and language are linked.

neuroscience↗

bioRxiv2024

Experience-dependent predictions of feedforward and contextual information in mouse visual cortex

To navigate complex environments, the visual system must prioritize unexpected inputs or omissions over predictable sensory backgrounds. This saliency assignment is a hallmark of visual processing and depends on comparing visual feedforward inputs with learned contextual surrounds, a process often conceptualized as a difference computation. However, cortical circuitry poses fundamental challenges: visual contextual feedback is predominantly amplifying, and feedback-driven inhibitory neurons necessary for subtractive computations are relatively sparse. How then can complex contextual feedback be selectively compared with feedforward input at the level of individual neurons? Here, we show that divergent plasticity rules within single pyramidal neurons provide a solution to this problem. Using two-photon calcium imaging, we recorded layer 2/3 pyramidal cell responses in mouse primary visual cortex before and after visual familiarization. We dissociated feedforward and contextual signals by comparing responses to stimuli with and without an occluded sector. Repeated feedforward responses selectively weakened through adaptation and surround suppression, whereas contextual responses strengthened and generalized across scenes. These strengthened contextual inputs amplified non-adapted responses to novel images and drove neuronal activity when occlusion of feedforward input prevented surround suppression. This produced a conserved structure of feedforward and contextual responses across mice, monkeys, and humans. Ultimately, these results reveal a cellular mechanism for saliency assignment that does not require feedback-driven inhibition. Pyramidal neurons autonomously learn the generalized statistical structure of familiar contexts, allowing them to selectively amplify improbable inputs or omissions.

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bioRxiv2023

Visuomotor experience induces functional and structural plasticity of chandelier cells

Detailed characterization of interneuron types in primary visual cortex (V1) has greatly contributed to understanding visual perception, yet the role of chandelier cells (ChCs) in visual processing remains poorly characterized. Using viral tracing we found that V1 ChCs predominantly receive monosynaptic input from local layer 5 pyramidal cells and higher-order cortical regions. Two-photon calcium imaging and convolutional neural network modelling revealed that ChCs are visually responsive but weakly selective for stimulus content. In mice running in a virtual tunnel, ChCs respond strongly to events known to elicit arousal, including locomotion and visuomotor mismatch. Repeated exposure of the mice to the virtual tunnel was accompanied by reduced visual responses of ChCs and structural plasticity of ChC boutons and axon initial segment length. Finally, ChCs only weakly inhibited pyramidal cells. These findings suggest that ChCs provide an arousal-related signal to layer 2/3 pyramidal cells that may modulate their activity and/or gate plasticity of their axon initial segments during behaviorally relevant events.

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bioRxiv2022

Feedback brings scene information to the representation of occluded image regions in area V1 of monkeys and humans

Neuronal activity in the primary visual cortex (V1) is driven by feedforward input from within the neurons receptive fields (RFs) and modulated by contextual information in regions surrounding the RF. The effect of contextual information on spiking activity occurs rapidly, and is therefore challenging to dissociate from feedforward input. To address this challenge, we recorded the spiking activity of V1 neurons in monkeys viewing either natural scenes or scenes where the information in the RF was occluded, effectively removing the feedforward input. We found that V1 neurons responded rapidly and selectively to occluded scenes. V1 responses elicited by occluded stimuli could be used to decode scene identity and could be predicted from those elicited by non-occluded images, indicating that there is overlap between visually-driven and contextual responses. We used representational similarity analysis to show that the structure of V1 representations of occluded scenes measured with electrophysiology in monkeys correlates strongly with the representations of the same scenes in humans measured with fMRI. Our results reveal that contextual influences alter the spiking activity of V1 in monkeys across large distances on a rapid time scale, carry information about scene identity and resemble those in human V1.

neuroscience↗

bioRxiv2022

Involvement of superior colliculus in complex figure detection of mice

Object detection is an essential function of the visual system. Although the visual cortex plays an important role in object detection, the superior colliculus can support detection when the visual cortex is ablated or silenced. Moreover, it has been shown that superficial layers of mouse SC (sSC) encode visual features of complex objects, and that this code is not inherited from the primary visual cortex. This suggests that mouse sSC may provide a significant contribution to complex object vision. Here, we use optogenetics to show that mouse sSC is causally involved in figure detection based on differences in figure contrast, orientation and phase. Additionally, our neural recordings show that in mouse sSC, image elements that belong to a figure elicit stronger activity than those same elements when they are part of the background. The discriminability of this neural code is higher for correct trials than incorrect trials. Our results provide new insight into the behavioral relevance of the visual processing that takes place in sSC.

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bioRxiv2022

The direct and indirect pathways of the basal ganglia antagonistically influence cortical activity and perceptual decisions

The striatum, input nucleus of the basal ganglia, receives topographically organized input from the cortex and gives rise to the direct and indirect pathways with antagonistic effects on the output of the basal ganglia. We optogenetically stimulated the direct and indirect pathways in mice and measured their influence on perceptual decisions and neuronal activity in the cortex. In a task in which mice had to detect a visual stimulus, unilateral direct-pathway stimulation increased the probability of lick responses to the non-stimulated side and increased cortical activity globally. In contrast, indirect-pathway stimulation increased the probability of licks to the stimulated side and decreased activity in visual cortical areas. To probe the possible role of the two pathways in working memory, we trained the mice to report the location of a stimulus with licking one of two spouts, after a memory delay. Direct-pathway stimulation prior to and during the memory delay enhanced both the neural representation of a contralateral visual stimulus and the number of contraversive choices, whereas indirect-pathway stimulation had the opposite effects, in accordance with an antagonistic influence of the direct and indirect pathways on licking direction. Our results demonstrate how these two pathways influence perceptual decisions and working memories, and modify activity in the cerebral cortex. One sentence summaryVisuomotor transformations are influenced antagonistically by the direct and indirect pathways of the basal ganglia during visual detection and working memory tasks

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bioRxiv2021

The influence of objecthood on the representation of natural images in the visual cortex

Neurons in early visual cortex are not only sensitive to the image elements in their receptive field but also to the context determining whether the elements are part of an object or background. We here assessed the effect of objecthood in natural images on neuronal activity in early visual cortex, with fMRI in humans and electrophysiology in monkeys. We report that boundaries and interiors of objects elicit more activity than the background. Boundary effects occur remarkably early, implying that visual cortical neurons are tuned to features characterizing object boundaries in natural images. When a new image is presented the influence of the object interiors on neuronal activity occurs during a late phase of neuronal response and earlier when eye movements shift the image representation, implying that object representations are remapped across eye-movements. Our results reveal how object perception shapes the representation of natural images in early visual cortex.

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bioRxiv2021

Intracortical human recordings reveal intensity coding for the pain of others in the insula

Based on neuroimaging data, the insula is considered important for people to empathize with the pain of others, whether that pain is perceived through facial expressions or the sight of limbs in painful situations. Here we present the first report of intracranial electroencephalographic (iEEG) recordings from the insulae collected while 7 presurgical epilepsy patients rated the intensity of a womans painful experiences viewed in movies. In two separate conditions, pain was deduced from seeing facial expressions or a hand being slapped by a belt. We found that broadband activity in the 20-190 Hz range correlated with the trial-by-trial perceived intensity in the insula for both types of stimuli. Using microwires at the tip of a selection of the electrodes, we additionally isolated 8 insular neurons with spiking that correlated with perceived intensity. Within the insula, we found a patchwork of locations with differing selectivities within our stimulus set, some representing intensity only for facial expressions, others only for the hand being hit, and others for both. That we found some locations with intensity coding only for faces, and others only for hand across simultaneously recorded locations suggests that insular activity while witnessing the pain of others cannot be entirely reduced to a univariate salience representation. Psychophysics and the temporal properties of our signals indicate that the timing of responses encoding intensity for the sight of the hand being hit are best explained by kinematic information; the timing of those encoding intensity for facial expressions are best explained by shape information in the face. In particular, the furrowing of the eyebrows and the narrowing of the eyes of the protagonist in the movies suffice to predict both the rating of and the timing of the neuronal response to the facial expressions. Comparing the broadband activity in the iEEG signal with spiking activity and an fMRI experiment with similar stimuli revealed a consistent spatial organization for the representation of intensity from our hand stimuli, with stronger intensity representation more anteriorly and around neurons with intensity coding. In contrast, for the facial expressions, we found that the activity at the three levels of measurement do not coincide, suggesting a more disorganized representation. Together, our intracranial recordings indicate that the insula encodes, in a partially intermixed layout, both static and dynamic cues from different body parts that reflect the intensity of pain experienced by others.

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bioRxiv2021

Oscillations support co-firing of neurons in the service of human memory formation

Theta and gamma oscillations in the medial temporal lobe are suggested to play a critical role for human memory formation via establishing synchrony in neural assemblies. Arguably, such synchrony facilitates efficient information transfer between neurons and enhances synaptic plasticity, both of which benefit episodic memory formation. However, to date little evidence exists from humans that would provide direct evidence for such a specific role of theta and gamma oscillations for episodic memory formation. Here we investigate how oscillations shape the temporal structure of neural firing during memory formation in the medial temporal lobe. We measured neural firing and local field potentials in human epilepsy patients via micro-wire electrode recordings to analyze how brain oscillations promote co-incidences of firing between neurons during successful and unsuccessful encoding of episodic memories. The results show that phase-coupling of neurons to faster theta and gamma oscillations correlates with co-firing at short latencies ([~]20-30 ms) and occurs during successful memory formation. Phase-coupling at slower oscillations in these same frequency bands, in contrast, correlates with longer co-firing latencies and occurs during memory failure. Thus, our findings provide evidence which implicate neural oscillations into the synchronization of neural firing in the medial temporal lobe during the encoding of episodic memories.

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bioRxiv2020

Human hippocampal neurons track moments in a sequence of events.

An indispensable feature of episodic memory is our ability to temporally piece together different elements of an experience into a coherent memory. Hippocampal "time cells" - neurons that represent temporal information - may play a critical role in this process. While these cells have been repeatedly found in rodents, it is still unclear to what extent similar temporal selectivity exists in the human hippocampus. Here we show that temporal context modulates the firing activity of human hippocampal neurons during structured temporal experiences. We recorded neuronal activity in the human brain while patients learned predictable sequences of pictures. We report that human time cells fire at successive moments in this task. Furthermore, time cells also signaled inherently changing temporal contexts during empty 10-second gap periods between trials, while participants waited for the task to resume. Finally, population activity allowed for decoding temporal epoch identity, both during sequence learning and during the gap periods. These findings suggest that human hippocampal neurons could play an essential role in temporally organizing distinct moments of an experience in episodic memory. Significance StatementEpisodic memory refers to our ability to remember the "what, where, and when" of a past experience. Representing time is an important component of this form of memory. Here, we show that neurons in the human hippocampus represent temporal information. This temporal signature was observed both when participants were actively engaged in a memory task, as well as during 10s-long gaps when they were asked to wait before performing the task. Furthermore, the activity of the population of hippocampal cells allowed for decoding one temporal epoch from another. These results suggest a robust representation of time in the human hippocampus.

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bioRxiv2019

Theta-phase dependent neuronal coding during sequence learning in human single neurons.

The ability to maintain a sequence of items in short-term memory (STM) is a fundamental cognitive function. In the rodent hippocampus, the representation of sequentially organized spatial locations is reflected by the phase of action potentials relative to the theta oscillation (phase precession). We investigated whether the timing of neuronal activity relative to the theta brain oscillation also reflects sequence order in the medial temporal lobe of humans. We used a task in which human subjects learned sequences of pictures and recorded single neuron and local field potential activity with implanted electrodes. We report that spikes for three consecutive items in the sequence (the preferred stimulus for each cell, as well as the stimuli immediately preceding and following it) were phase-locked at distinct phases of the theta oscillation. Consistent with phase precession, spikes were fired at progressively earlier phases as the sequence advanced. These findings generalize previous findings in the rodent hippocampus to the human temporal lobe and suggest that encoding stimulus information at distinct oscillatory phases may play a role in maintaining their sequential order in STM.

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bioRxiv2018

Feedforward and feedback processing during figure-ground perception in mice

The segregation of figures from the background is an important step in visual perception. In primary visual cortex, figures evoke stronger activity than backgrounds during a delayed phase of the neuronal responses, but it is unknown how this figure-ground modulation (FGM) arises and whether it is necessary for perception. Here we show, using optogenetic silencing in mice, that the delayed V1 response phase is necessary for figure-ground segregation. Neurons in higher visual areas also exhibit FGM and optogenetic silencing of higher areas reduced FGM in V1. In V1, figures elicited higher activity of vasoactive intestinal peptide-expressing (VIP) interneurons than the background, whereas figures suppressed somatostatin-positive interneurons, resulting in an increased activation of pyramidal cells. Optogenetic silencing of VIP neurons reduced FGM in V1, indicating that disinhibitory circuits contribute to FGM. Our results provide new insight in how lower and higher areas of the visual cortex interact to shape visual perception.

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