Biology subjects

Rhone, A. E.

Publications and source records attributed to Rhone, A. E..

11 recordsLinked to original sources

bioRxiv2026

Hippocampal-cingulate dynamics in the human brain link reinforcement-learning and memory

Reinforcement learning (RL) models describe how reward computations shape our choices, but whether the same computations also shape memory in the human brain is unclear. To address this question, we combined multi-areal intracranial recordings with computational modeling of reward and memory in neurosurgical patients. Patients played a gambling task in which decisions yielded monetary rewards tied to trial-unique images, followed immediately by a recognition test for those images. Model-derived positive reward prediction errors (RPEs) predicted later memory for each image. During feedback, multivariate high-frequency activity revealed the spatiotemporal evolution of RPE representations across distributed prefrontal cortex. During subsequent recognition, however, only anterior cingulate cortex (ACC) transiently reinstated RPE representations, and successful recognition specifically associated with hippocampal reinstatement of these ACC representations. Hippocampal-cingulate theta synchrony scaled with RPE during recognition, alongside hippocampal theta decoding of upcoming memory choices. Thus, the RL computations that guide decision-making also shape memory through hippocampal-cingulate circuit dynamics in the human brain.

neuroscience↗

bioRxiv2026

Cycle-by-cycle respiration waveforms are coupled with the shape of neural oscillations

Beyond sustaining life, breathing is a vital physiological rhythm that shapes cognition, perception, emotional regulation, and mental health. Breathing has a direct effect on neuronal excitability and is coupled to neural oscillations across a variety of brain regions. Notably, both respiration and neural oscillations are asymmetric and not perfectly rhythmic: for example, every breath has a different shape and duration, and is interspersed with variable pauses. Here, we examined the coupling between breathing and the brain by quantifying the nonsinusoidal features of each breath and comparing it to the shape of each corresponding neural oscillation cycle. By leveraging invasive human brain recordings from 16 participants, we found respiration-neural waveform coupling on a breath-by-breath, cycle-by-cycle basis across limbic and cortical forebrain regions. For decades, the dominant perspective on cognition and mental health have focused on the brain, but recent work is highlighting the importance of brain-body interactions. Our results show that the coupling between breathing and neural activity is much richer than previously appreciated, and our approach opens new avenues for studying these peripheral-to-central nervous system interactions in a more robust, temporally precise manner.

neuroscience↗

bioRxiv2026

Transcranial magnetic stimulation to the dorsolateral prefrontal cortex modulates single-neuron activity in humans

Transcranial magnetic stimulation (TMS) to the dorsolateral prefrontal cortex (dlPFC) is an FDA-cleared treatment for depression, yet how cortical stimulation influences single neurons in deep brain circuits remains unknown. Using intracranial microelectrode recordings in four neurosurgical patients, we resolved single-neuron spikes as early as 8 ms from 185 single neurons after single-pulse left dlPFC TMS. TMS elicited time-locked firing responses in 46% of neurons across deep cortical and subcortical structures bilaterally. TMS facilitated putative interneuron spiking in striato-thalamic regions from [~]8 ms, peaking at [~]80-100 ms, and lasting to [~]1000 ms, while suppressing putative pyramidal cell spiking with a delayed and slower time course. Trial-by-trial single-neuron modulations were positively correlated with cortico-striato-thalamic network activity and anti-correlated with limbic network activity. These findings reveal that dlPFC TMS facilitates inhibitory firing in executive control networks while suppressing limbic excitatory drive, providing a cellular mechanism for how cortical stimulation modulates distributed brain networks.

neuroscience↗

bioRxiv2025

Brain-wide single-neuron bases of working memory for sounds in humans

In order to understand the constantly changing acoustic world our brains must maintain elements of auditory scenes in memory. The neural mechanisms for this fundamental process remain unclear. Here, we report human intracranial recordings of 1269 single neurons while participants performed a non-verbal auditory working memory task that required adjustment of a tone frequency to match a target. We found neurons within hippocampus, insula and cingulate cortex, for which firing rates were modulated at different phases of the task, particularly during maintenance and adjustment. For the majority of the neurons modulated during maintenance there was a striking suppression of activity rather than increased activity. Across the entire neuronal population, state-space analysis demonstrated attractor-like states corresponding to different task phases. Behaviorally, more neurons were modulated at the beginning of the maintenance phase in trials when participants performed better. State-space analysis was consistent with greater attractor-like activity during the adjustment phase supporting better performance. These data support the existence of a widely distributed neural code for auditory working memory that determines related behavior based on attractor-like states.

neuroscience↗

bioRxiv2025

Reading specific memories from human neurons before and after sleep

The ability to retrieve a single episode encountered just once is a hallmark of human intelligence and episodic memory[1]. Yet, decoding a specific memory from neuronal activity in the human brain remains a formidable challenge. Here, we develop a transformer neural network model[2, 3] trained on neuronal spikes from intracranial microelectrodes recorded during a single viewing of an audiovisual episode. Combining spikes throughout the brain via cross-channel attention[4], capable of discovering neural patterns spread across brain regions and timescales, individual participant models predict vocalization of specific concepts such as persons or places during out-of-distribution memory recall. Brain regions differentially contribute to memory decoding before and after sleep. Models trained using only medial temporal lobe (MTL) spikes significantly decode concepts before but not after sleep, while models trained using only frontal cortex (FC) spikes decode concepts after but not before sleep, with better FC decoding relating to increased non-REM sleep. These findings suggest a system-wide distribution of information across neural populations that transforms over wake/sleep cycles[5]. Such decoding of internally generated memories suggests a path towards brain-computer interfaces to treat episodic memory disorders through enhancement or muting of specific memories.

neuroscience↗

bioRxiv2024

Traveling waves shape neural population dynamics enabling predictions and internal model updating

The brain generates predictions based on statistical regularities in our environment. However, it is unclear how predictions are optimized through iterative interactions with the environment. Because traveling waves (TWs) propagate across the cortex shaping neural excitability, they can carry information to serve predictive processing. Using human intracranial recordings, we show that anterior-to-posterior alpha TWs correlated with prediction strength. Learning about priors altered neural state space trajectories, and how much it altered correlated with trial-by-trial prediction strength. Learning involved mismatches between predictions and sensory evidence triggering alpha-phase resets in lateral temporal cortex, accompanied by stronger alpha phase-high gamma amplitude coupling and high-gamma power. The mismatch initiated posterior-to-anterior alpha TWs and change in the subsequent trials state space trajectory, facilitating model updating. Our findings suggest a vital role of alpha TWs carrying both predictions to sensory cortex and mismatch signals to frontal cortex for trial-by-trial fine-tuning of predictive models.

neuroscience↗

bioRxiv2023

Activity-induced gene expression in the human brain

Direct electrical stimulation (eSTIM) is widely used clinically, from neurosurgical mapping to therapeutic interventions for neurological and neuropsychiatric disorders1-10. Despite over a century of application, its molecular and cellular underpinnings remain unknown. Here, using state-of-the-art single-nuclei multiomic profiling, we map changes in cell-type-specific gene expression and chromatin accessibility in vivo in the human cortex following eSTIM of neurosurgery patients. eSTIM impacts a network of cells that extends beyond excitatory neurons to include inhibitory neurons, astrocytes, oligodendrocytes and microglia. We observed an upregulation of canonical immediate-early genes (IEGs: FOS, NPAS4, EGR4) in excitatory and inhibitory neurons and induction of cytokine-related genes CCL3 and CCL4 in microglia. The cross-species conservation of this gene signature, together with our examination of a cohort of both epilepsy and cancer patients, underscores the fundamental role of these changes in stimulation-driven plasticity while controlling for disease and environmental confounds. Our study of changes in chromatin accessibility reveals a common code that involves a cell-type specific signature of transcription factor binding motifs for members of the EGR family. By addressing these previously unexplored questions about activity-induced gene expression in vivo in the human brain, our findings challenge the long-standing neuron-centric view of eSTIM, highlighting the broader role of non-neuronal cells, including microglia, in mediating the impact of brain stimulation.

neuroscience↗

bioRxiv2022

Immediate neural network impact after the loss of a semantic hub

The human brain extracts meaning from the world using an extensive neural system for semantic knowledge. Whether such broadly distributed systems1-3 crucially depend on or can compensate for the loss of one of their highly interconnected hubs4-6 is controversial4. The strongest level of causal evidence for the role of a brain hub is to evaluate its acute network-level impact following disconnection and any rapid functional compensation that ensues. We report rare neurophysiological data from two patients who underwent awake intracranial recordings during a speech prediction task immediately before and after neurosurgical treatment that required disconnection of the left anterior temporal lobe (ATL), a crucial hub for semantic knowledge4-6. Informed by a predictive coding framework, we tested three sets of hypotheses including diaschisis causing disruption in interconnected sites7 and incomplete or complete compensation by other language-critical and speech processing sites8-10. Immediately after ATL disconnection, we observed highly specific neurophysiological alterations in the recorded fronto-temporal network, including abnormally magnified high gamma responses to the speech sounds in auditory cortex. We also observed evidence for rapid compensation, seen as focal increases in effective connectivity involving language-critical sites in the inferior frontal gyrus and speech processing sites in auditory cortex. However, compensation was incomplete, in part because after ATL disconnection speech prediction signals were depleted in auditory cortex. This study provides direct causal evidence for a semantic hub in the human brain and shows striking neural impact and a rapid attempt at compensation in a neural network after the loss of one of its hubs.

neuroscience↗

bioRxiv2020

Common Fronto-temporal Effective Connectivity in Humans and Monkeys

Cognitive pathways supporting human language and declarative memory are thought to have uniquely evolutionarily differentiated in our species. However, cross-species comparisons are missing on site-specific effective connectivity between regions important for cognition. We harnessed a new approach using functional imaging to visualize the impact of direct electrical brain stimulation in human neurosurgery patients. Applying the same approach with macaque monkeys, we found remarkably comparable patterns of effective connectivity between auditory cortex and ventro-lateral prefrontal cortex (vlPFC) and parahippocampal cortex in both species. Moreover, in humans electrical tractography revealed rapid evoked potentials in vlPFC from stimulating auditory cortex and speech sounds drove vlPFC, consistent with prior evidence in monkeys of direct projections from auditory cortex to vocalization responsive regions in vlPFC. The results identify a common effective connectivity signature that from auditory cortex is equally direct to vlPFC and indirect to the hippocampus (via parahippocampal cortex) in human and nonhuman primates. HighlightsO_LIPrivileged human auditory to inferior frontal connectivity, linked to monkeys C_LIO_LICommon auditory to parahippocampal effective connectivity in both species C_LIO_LIGreater lateralization in human effective connectivity, more symmetrical in monkeys C_LIO_LIHuman fronto-temporal network function rooted in evolutionarily conserved signature C_LI eTOC short summaryFunctional connectivity between regions crucial for language and declarative memory is thought to have substantially differentiated in humans. Using a new technique to similarly visualize directional effective connectivity in humans and monkeys, we found remarkably comparable connectivity patterns in both species between fronto-temporal regions crucial for cognition.

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bioRxiv2019

A sound-sensitive source of alpha oscillations in human non-primary auditory cortex

The functional organization of human auditory cortex can be probed by characterizing responses to various classes of sound at different anatomical locations. Along with histological studies this approach has revealed a primary field in posteromedial Heschls gyrus (HG) with pronounced induced high-frequency (70-150 Hz) activity and short-latency responses that phase-lock to rapid transient sounds. Low-frequency neural oscillations are also relevant to stimulus processing and information flow, however their distribution within auditory cortex has not been established. Alpha activity (7-14 Hz) in particular has been associated with processes that may differentially engage earlier versus later levels of the cortical hierarchy, including functional inhibition and the communication of sensory predictions. These theories derive largely from the study of occipitoparietal sources readily detectable in scalp electroencephalography. To characterize the anatomical basis and functional significance of less accessible temporal-lobe alpha activity we analyzed responses to sentences in seven human adults (four female) with epilepsy who had been implanted with electrodes in superior temporal cortex. In contrast to primary cortex in posteromedial HG, a non-primary field in anterolateral HG was characterized by high spontaneous alpha activity that was strongly suppressed during auditory stimulation. Alpha-power suppression decreased with distance from anterolateral HG throughout superior temporal cortex, and was more pronounced for clear compared to degraded speech. This suppression could not be accounted for solely by a change in the slope of the power spectrum. The differential manifestation and stimulus-sensitivity of alpha oscillations across auditory fields should be accounted for in theories of their generation and function.\n\nSignificance StatementTo understand how auditory cortex is organized in support of perception, we recorded from patients implanted with electrodes for clinical reasons. This allowed measurement of activity in brain regions at different levels of sensory processing. Oscillations in the alpha range (7-14 Hz) have been associated with functions including sensory prediction and inhibition of regions handling irrelevant information, but their distribution within auditory cortex is not known. A key finding was that these oscillations dominated in one particular non-primary field, anterolateral Heschls gyrus, and were suppressed when subjects listened to sentences. These results build on our knowledge of the functional organization of auditory cortex and provide anatomical constraints on theories of the generation and function of alpha oscillations.

neuroscience↗

bioRxiv2018

Processing of Auditory Novelty Across the Cortical Hierarchy: An Intracranial Electrophysiology Study

Under the predictive coding hypothesis, specific spatiotemporal patterns of cortical activation are postulated to occur during sensory processing as expectations generate feedback predictions and prediction errors generate feedforward signals. Establishing experimental evidence for this information flow within cortical hierarchy has been difficult, especially in humans, due to spatial and temporal limitations of non-invasive measures of cortical activity. This study investigated cortical responses to auditory novelty using the local/global deviant paradigm, which engages the hierarchical network underlying auditory predictive coding over short ( local deviance; LD) and long ( global deviance; GD) time scales. Electrocorticographic responses to auditory stimuli were obtained in neurosurgical patients from regions of interest (ROIs) including auditory, auditory-related and prefrontal cortex. LD and GD effects were assayed in averaged evoked potential (AEP) and high gamma (70-150 Hz) signals, the former likely dominated by local synaptic currents and the latter largely reflecting local spiking activity. AEP LD effects were distributed across all ROIs, with greatest percentage of significant sites in core and non-core auditory cortex. High gamma LD effects were localized primarily to auditory cortex in the superior temporal plane and on the lateral surface of the superior temporal gyrus (STG). LD effects exhibited progressively longer latencies in core, non-core, auditory-related and prefrontal cortices, consistent with feedforward signaling. The spatial distribution of AEP GD effects overlapped that of LD effects, but high gamma GD effects were more restricted to non-core areas. High gamma GD effects had shortest latencies in STG and preceded AEP GD effects in most ROIs. This latency profile, along with the paucity of high gamma GD effects in the superior temporal plane, suggest that the STG plays a prominent role in initiating novelty detection signals over long time scales. Thus, the data demonstrate distinct patterns of information flow in human cortex associated with auditory novelty detection over multiple time scales.

neuroscience↗