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Introduction
The Miller Lab investigates the neural foundations of cognition. Our research has led to significant discoveries in areas such as working memory, attention, categorization, and top-down ‘executive’ control. We have provided new insights into how neural dynamics influence perception, thought, and action, and have pioneered the study of multifunctional ‘mixed selectivity’ neurons and their role in neural computation. The knowledge derived from our work is crucial for understanding cognitive functi
Skills and Expertise
Publications
Publications (269)
Ketamine is an N-methyl-D-aspartate (NMDA)-receptor antagonist that produces sedation, analgesia, and dissociation at low doses and profound unconsciousness with antinociception at high doses. At high and low doses, ketamine can generate gamma oscillations (>25 Hz) in the electroencephalogram (EEG). The gamma oscillations are interrupted by slow-de...
Ketamine is an NMDA-receptor antagonist that produces sedation, analgesia and dissociation at low doses and profound unconsciousness with antinociception at high doses. At high and low doses, ketamine can generate gamma oscillations ( > 25 Hz) in the electroencephalogram (EEG). The gamma oscillations are interrupted by slow-delta oscillations (0.1-...
Decoding vision is an ambitious task as it aims to transform scalar brain activity into dynamic images with refined shapes, colors and movements. In familiar environments, the brain may trigger activity that resembles specific pattern, thereby facilitating decoding. Can an artificial neural network (ANN) decipher such latent patterns? Here, we expl...
Many different anesthetics cause loss of responsiveness despite having diverse underlying molecular and circuit actions. To explore the convergent effects of these drugs, we examined how ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, and dexmedetomidine, an alpha2 adrenergic receptor agonist, affected neural oscillations in the prefr...
Cortical activity shows stability, including the ability to recover from disruptions. We analyzed spiking from the prefrontal cortex (PFC) of monkeys performing working memory tasks with mid-memory-delay distractions. Perturbation of cortex by events (a gaze shift or visual inputs) caused rotational dynamics in subspace that could return spiking to...
Cortical activity shows stability, including the ability to recover from disruptions. We analyzed spiking from the prefrontal cortex (PFC) of monkeys performing working memory tasks with mid-memory-delay distractions. Perturbation of cortex by events (a gaze shift or visual inputs) caused rotational dynamics in subspace that could return spiking to...
The mammalian cerebral cortex is anatomically organized into a six-layer motif. It is currently unknown whether a corresponding laminar motif of neuronal activity patterns exists across the cortex. Here we report such a motif in the power of local field potentials (LFPs). Using laminar probes, we recorded LFPs from 14 cortical areas across the cort...
Prefrontal cortex (PFC) is known to modulate the visual system to favor goal-relevant information by accentuating task-relevant stimulus dimensions. Does the brain broadly re-configures itself to optimize performance by stretching visual representations along task-relevant dimensions? We considered a task that required monkeys to selectively attend...
Every day, hundreds of thousands of people undergo general anesthesia. One hypothesis is that anesthesia disrupts dynamic stability, the ability of the brain to balance excitability with the need to be stable and thus controllable. We tested this hypothesis using a new method for quantifying population-level dynamic stability in complex systems, De...
To examine the biological building blocks of thought and action, we created biologically realistic local circuits based on detailed well-cited physiological and anatomical characteristics. These biomimetic circuits were then integrated into a large-scale model of cortical-striatal interactions for category learning. The model was not trained on, bu...
Research in human volunteers and surgical patients has shown that unconsciousness under general anesthesia can be reliably tracked using real-time electroencephalogram processing. Hence, a closed-loop anesthesia delivery (CLAD) system that maintains precisely specified levels of unconsciousness is feasible and would greatly aid intraoperative patie...
A critical component of anesthesia is the loss of sensory perception. Propofol is the most widely used drug for general anesthesia, but the neural mechanisms of how and when it disrupts sensory processing are not fully understood. We analyzed local field potential and spiking recorded from Utah arrays in auditory cortex, associative cortex, and cog...
In this editorial, Drs Peppercorn and noted neuroscientists Miller and Hasselmo comment on a recent randomized trial of music to reduce stress during infusion, noting that our understanding of the brain supports a unique and particularly effective role for music in improving mood and reducing distress for patients with cancer
Recording and modulating neural activity in vivo enables investigations of the neurophysiology underlying behavior and disease. However, there is a dearth of translational tools for simultaneous recording and localized receptor-specific modulation. We address this limitation by translating multifunctional fiber neurotechnology previously only avail...
Predictive coding is a fundamental function of the cortex. The predictive routing model proposes a neurophysiological implementation for predictive coding. Predictions are fed back from deep-layer cortex via alpha/beta (8-30Hz) oscillations. They inhibit the gamma (40-100Hz) and spiking that feed sensory inputs forward. Unpredicted inputs arrive in...
It is increasingly clear that memories are distributed across multiple brain areas. Such "engram complexes" are important features of memory formation and consolidation. Here, we test the hypothesis that engram complexes are formed in part by bioelectric fields that sculpt and guide the neural activity and tie together the areas that participate in...
A critical component of anesthesia is the loss sensory perception. Propofol is the most widely used drug for general anesthesia, but the neural mechanisms of how and when it disrupts sensory processing are not fully understood. We analyzed local field potential (LFP) and spiking recorded from Utah arrays in auditory cortex, associative cortex, and...
We propose and present converging evidence for the Cytoelectric Coupling Hypothesis: Electric fields generated by neurons are causal down to the level of the cytoskeleton. This could be achieved via electrodiffusion and mechanotransduction and exchanges between electrical, potential and chemical energy. Ephaptic coupling organizes neural activity,...
Previous work has identified stimulus specific time cells as a potential mechanism for working memory maintenance. It has been proposed that populations of stimulus specific sequences of cells could support memory for many items in a list over long periods of time. This would require information about one stimulus to persist after the presentation...
Working memory (WM) allows us to remember and selectively control a limited set of items. Neural evidence suggests it is achieved by interactions between bursts of beta and gamma oscillations. However, it is not clear how oscillations, reflecting coherent activity of millions of neurons, can selectively control individual WM items. Here we propose...
It is increasingly clear that memories are distributed across multiple brain areas. Such “engram complexes” are important features of memory formation and consolidation. Here, we test the hypothesis that engram complexes are formed in part by bioelectric fields that sculpt and guide the neural activity and tie together the areas that participate in...
Cortical function emerges from the interactions of multi-scale networks that may be studied at a high level using neural mass models (NMM) that represent the mean activity of large numbers of neurons. Here, we provide first a new framework called laminar NMM, or LaNMM for short, where we combine conduction physics with NMMs to simulate electrophysi...
Distinct dynamics in different cortical layers are apparent in neuronal and local field potential (LFP) patterns, yet their associations in the context of laminar processing have been sparingly analyzed. Here, we study the laminar organization of spike-field causal flow within and across visual (V4) and frontal areas (PFC) of monkeys performing a v...
Working memory has long been thought to arise from sustained spiking/attractor dynamics. However, recent work has suggested that short-term synaptic plasticity (STSP) may help maintain attractor states over gaps in time with little or no spiking. To determine if STSP endows additional functional advantages, we trained artificial recurrent neural ne...
Working memory is where thoughts are held and manipulated. For many years, the dominant model was that working memory relied on steady-state neural dynamics. A neural representation was activated and then held in that state. However, as often happens, the more we examine working memory (especially with new technology), the more complex it looks. Re...
Recording and modulating neural activity in vivo enables investigations of neural circuits during behavior. However, there is a dearth of tools for simultaneous recording and localized receptor modulation in large animal models. We address this limitation by translating multifunctional fiber-based neurotechnology previously only available for roden...
The mammalian cerebral cortex is anatomically organized into a six-layer motif. It is currently unknown whether a corresponding laminar motif of neuronal activity exists across the cortex. Here, we report the discovery of such a motif in the power of local field potentials (LFP). We implanted multicontact laminar probes in five macaque monkeys and...
Working memories have long been thought to be maintained by persistent spiking. However, mounting evidence from multiple-electrode recording (and single-trial analyses) shows that the underlying spiking is better characterized by intermittent bursts of activity. A counterargument suggested this intermittent activity is at odds with observations tha...
Cortical function emerges from the interactions of multi-scale networks that may be studied at a high level using neural mass models (NMM), representing the mean activity of large numbers of neurons. In order to properly reproduce experimental data, these models require the addition of further elements. Here we provide a framework integrating condu...
In neuroscience, the term ‘causality’ is used to refer to different concepts, leading to confusion. Here we illustrate some of those variations, and we suggest names for them. We then introduce four ways to enhance clarity around causality in neuroscience.
Oscillatory dynamics in cortex seem to organize into traveling waves that serve a variety of functions. Recent studies show that propofol, a widely used anesthetic, dramatically alters cortical oscillations by increasing slow-delta oscillatory power and coherence. It is not known how this affects traveling waves. We compared traveling waves across...
It is known that the exact neurons maintaining a given memory (the neural ensemble) change from trial to trial. This raises the question of how the brain achieves stability in the face of this representational drift. Here, we demonstrate that this stability emerges at the level of the electric fields that arise from neural activity. We show that el...
Working memories have long been thought to be maintained by persistent spiking. However, mounting evidence from multiple-electrode recording (and single-trial analyses) shows that the underlying spiking is better characterized by intermittent bursts of activity. A counterargument suggested this intermittent activity is at odds with observations tha...
Neural oscillations are evident across cortex but their spatial structure is not well- explored. Are oscillations stationary or do they form “traveling waves”, i.e., spatially organized patterns whose peaks and troughs move sequentially across cortex? Here, we show that oscillations in the prefrontal cortex (PFC) organized as traveling waves in the...
Oscillatory dynamics in cortex seem to organize into traveling waves that serve a variety of functions. Recent studies show that propofol, a widely used anesthetic, dramatically alters cortical oscillations by increasing slow-delta oscillatory power and coherence. It is not known how this affects traveling waves. We compared traveling waves across...
Working memory has long been thought to arise from sustained spiking/attractor dynamics. However, recent work has suggested that short-term synaptic plasticity (STSP) may help maintain attractor states over gaps in time with little or no spiking. To determine if STSP endows additional functional advantages, we trained artificial recurrent neural ne...
Foreword from the editors.
We hosted four keynote speakers: Wolf Singer, Bill Bialek, Danielle Bassett, and Sonja Gruen. They enlightened us about computations in the cerebral cortex, the reduction of high-dimensional data, the emerging field of computational psychiatry, and the significance of spike patterns in motor cortex. From the submissions,...
Continuous monitoring of electroencephalogram (EEG) recordings in humans under general anesthesia (GA) has demonstrated that changes in EEG dynamics induced by an anesthetic drug are reliably associated with the altered arousal states caused by the drug. This observation suggests that an intelligent, closed-loop anesthesia delivery (CLAD) system op...
It is known that the exact neurons maintaining a given memory (the neural ensemble) change from trial to trial. This raises the question of how the brain achieves stability in the face of this representational drift. Here, we demonstrate that this stability emerges at the level of the electric fields that arise from neural activity. We show that el...
Ketamine is an NMDA receptor antagonist commonly used to maintain general anesthesia. At anesthetic doses, ketamine causes high power gamma (25-50 Hz) oscillations alternating with slow-delta (0.1-4 Hz) oscillations. These dynamics are readily observed in local field potentials (LFPs) of non-human primates (NHPs) and electroencephalogram (EEG) reco...
The specific circuit mechanisms through which anesthetics induce unconsciousness have not been completely characterized. We recorded neural activity from the frontal, parietal, and temporal cortices and thalamus while maintaining unconsciousness in non-human primates (NHPs) with the anesthetic propofol. Unconsciousness was marked by slow frequency...
Neural oscillations are evident across cortex but their spatial structure is not well-explored. Are oscillations stationary or do they form “traveling waves”, i.e., spatially organized patterns whose peaks and troughs move sequentially across cortex? Here, we show that oscillations in the prefrontal cortex (PFC) organized as traveling waves in the...
Visual working memory (WM) storage is largely independent between the left and right visual hemifields/cerebral hemispheres, yet somehow WM feels seamless. We studied how WM is integrated across hemifields by recording neural activity bilaterally from lateral prefrontal cortex. An instructed saccade during the WM delay shifted the remembered locati...
Working memory allows us to selectively remember and flexibly manipulate a limited amount of information. Importantly, once we learn a certain operation, it generalizes to any memory object, not just the objects it has been trained on. Here we propose a conceptual model for how this might be achieved on the neural network level. It relies on spatia...
Significance
An established theoretical model, predictive coding, states that the brain is constantly building models (signifying changing predictions) of the environment. The brain does this by forming predictions and signaling sensory inputs which deviate from predictions (“prediction errors”). Various hypotheses exist about how predictive coding...
Adaptive memory requires the organism to form associations that bridge between events separated in time. Many studies show interactions between hippocampus (HPC) and prefrontal cortex (PFC) during formation of such associations. We analyze neural recording from monkey HPC and PFC during a memory task that requires the monkey to associate stimuli se...
Neural activity is organized at multiple scales, ranging from the cellular to the whole brain level. Connecting neural dynamics at different scales is important for understanding brain pathology. Neurological diseases and disorders arise from interactions between factors that are expressed in multiple scales. Here, we suggest a new way to link micr...
Ketamine is an NMDA receptor antagonist commonly used to maintain general anesthesia. At anesthetic doses, ketamine causes bursts of 30-50 Hz oscillations alternating with 0.1 to 10 Hz oscillations. These dynamics are readily observed in local field potentials (LFPs) of non-human primates (NHPs) and electroencephalogram (EEG) recordings from human...
Visual working memory (WM) storage is largely independent between the left and right visual hemifields/cerebral hemispheres, yet somehow WM feels seamless. We studied how WM is integrated across hemifields by recording neural activity bilaterally from lateral prefrontal cortex. An instructed saccade during the WM delay shifted the remembered locati...
The brain consists of many interconnected networks with time-varying, partially autonomous activity. There are multiple sources of noise and variation yet activity has to eventually converge to a stable, reproducible state (or sequence of states) for its computations to make sense. We approached this problem from a control-theory perspective by app...
Many large-scale functional connectivity studies have emphasized the importance of communication through increased inter-region correlations during task states. In contrast, local circuit studies have demonstrated that task states primarily reduce correlations among pairs of neurons, likely enhancing their information coding by suppressing shared s...
The specific circuit mechanisms through which anesthetics induce unconsciousness have not been completely characterized. We recorded neural activity from the frontal, parietal, and temporal cortices and thalamus while maintaining unconsciousness in non-human primates (NHPs) with the anesthetic propofol. Unconsciousness was marked by slow frequency...
2020 Elsevier Inc. Optogenetics is among the most widely employed techniques to manipulate neuronal activity. However, a major drawback is the need for invasive implantation of optical fibers. To develop a minimally invasive optogenetic method that overcomes this challenge, we engineered a new step-function opsin with ultra-high light sensitivity (...
Theta (2–8 Hz), alpha (8–12 Hz), beta (12–35 Hz), and gamma (>35 Hz) rhythms are ubiquitous in the cortex. However, there is little understanding of whether they have similar properties and functions in different cortical areas because they have rarely been compared across them. We record neuronal spikes and local field potentials simultaneously at...
Cognition involves using attended information, maintained in working memory (WM), to guide action. During a cognitive task, a correct response requires flexible, selective gating so that only the appropriate information flows from WM to downstream effectors that carry out the response. In this work, we used biophysically-detailed modeling to explor...
Institute of Mathematical Statistics, 2020. Angular measurements are often modeled as circular random variables, where there are natural circular analogues of moments, including correlation. Because a product of circles is a torus, a d-dimensional vector of circular random variables lies on a d-dimensional torus. For such vectors we present here a...
The sixth edition of the foundational reference on cognitive neuroscience, with entirely new material that covers the latest research, experimental approaches, and measurement methodologies. Each edition of this classic reference has proved to be a benchmark in the developing field of cognitive neuroscience. The sixth edition of The Cognitive Neuro...
Large-scale neuronal recording techniques have enabled discoveries of population-level mechanisms for neural computation. However, it is not clear how these mechanisms form by trial-and-error learning. In this article, we present an initial effort to characterize the population activity in monkey prefrontal cortex (pFC) and hippocampus during the l...
Neural activity is organized at multiple scales, ranging from the cellular to the whole brain level. Connecting neural dynamics at different scales is important for understanding brain pathology. Neurological diseases and disorders arise from interactions between factors that are expressed in multiple scales. Here, we suggest a new way to link micr...
Optogenetics is among the most widely employed techniques to manipulate neuronal activity. However, a major drawback is the need for invasive implantation of optical fibers. To develop a minimally invasive optogenetic method that overcomes this challenge, we engineered a new step-function opsin with ultra-high light sensitivity (SOUL). We show that...
Theta (2-8 Hz), Alpha (8-12 Hz), beta (12-35 Hz) and gamma (>35 Hz) rhythms are ubiquitous in cortex. But there is little understanding of whether they have similar properties and functions in different cortical areas because they have rarely been compared across them. We record neuronal spikes and local field potentials simultaneously at several l...
In predictive coding, experience generates predictions that attenuate the feeding forward of predicted stimuli while passing forward unpredicted errors. Different models have different neural implementations of predictive coding. We recorded spikes and local field potentials from laminar electrodes in five cortical areas (V4, LIP, area 7A, FEF, and...
The brain consists of many interconnected networks with time-varying, partially autonomous activity. There are multiple sources of noise and variation yet activity has to eventually converge to a stable, reproducible state (or sequence of states) for its computations to make sense. We approached this problem from a control-theory perspective by app...
2020 National Academy of Sciences. All rights reserved. In predictive coding, experience generates predictions that attenuate the feeding forward of predicted stimuli while passing forward unpredicted "errors." Different models have suggested distinct cortical layers, and rhythms implement predictive coding. We recorded spikes and local field poten...
Angular measurements are often modeled as circular random variables, where there are natural circular analogues of moments, including correlation. Because a product of circles is a torus, a d-dimensional vector of circular random variables lies on a d-dimensional torus. For such vectors we present here a class of graphical models, which we call tor...
We know that general anesthesia produces unconsciousness but not quite how. We recorded neural activity from the frontal, parietal, and temporal cortices and thalamus while maintaining unconsciousness in non-human primates (NHPs) with propofol. Unconsciousness was marked by slow frequency (~1 Hz) oscillations in local field potentials, entraining l...
Cerebral cortex is composed of 6 anatomical layers. How these layers contribute to computations that give rise to cognition remains a challenge in neuroscience. Part of this challenge is to reliably identify laminar markers from in-vivo neurophysiological data. Classic methods for laminar identification are based on assumptions which are often viol...
National Institute of Mental Health (Award 5R37MH087027)
Many recent advances in artificial intelligence (AI) are rooted in visual neuroscience. However, ideas from more complicated paradigms like decision-making are less used. Although automated decision-making systems are ubiquitous (driverless cars, pilot support systems, medical diagnosis algorithms etc.), achieving human-level performance in decisio...
Understanding the function of different neuronal cell types is key to understanding brain function. However, cell-type diversity is typically overlooked in electrophysiological studies in awake behaving animals. Here, we show that four functionally distinct cell classes can be robustly identified from extracellular recordings in several cortical re...
Adaptive memory requires the organism to form associations that bridge between events separated in time. Many studies show interactions between hippocampus (HPC) and prefrontal cortex (PFC) during formation of such associations. We analyze neural recording from monkey HPC and PFC during a memory task that requires the monkey to associate stimuli se...
It remains challenging to relate EEG and MEG to underlying circuit processes and comparable experiments on both spatial scales are rare. To close this gap between invasive and non-invasive electrophysiology we developed and recorded human-comparable EEG in macaque monkeys during visual stimulation with colored dynamic random dot patterns. Furthermo...
Neural rhythms or oscillations are ubiquitous in neuroimaging data. These spectral responses have been linked to several cognitive processes; including working memory, attention, perceptual binding and neuronal coordination. In this paper, we show how Bayesian methods can be used to finesse the ill-posed problem of reconstructing—and explaining—osc...
The brain consists of many interconnected networks with time-varying activity. There are multiple sources of noise and variation yet activity has to eventually converge to a stable state for its computations to make sense. We approached this from a control-theory perspective by applying contraction analysis to recurrent neural networks. This allowe...
Mental disorders often involve difficulty with complex cognitive functions, such as decision making, emotional self-regulation, or behavioral adaptation to changing circumstances. Those functions arise from the carefully timed and orchestrated synchrony of activity across multiple structures¹—in other words, from network activity. It should therefo...
Deep brain stimulation (DBS) is a circuit-oriented treatment for mental disorders. Unfortunately, even well-conducted psychiatric DBS clinical trials have yielded inconsistent symptom relief, in part because DBS’ mechanism(s) of action are unclear. One clue to those mechanisms may lie in the efficacy of ventral internal capsule/ventral striatum (VC...
Large-scale neuronal recording techniques have enabled discoveries of population-level mechanisms for neural computation. However it is not clear how these mechanisms form by trial and error learning. In this paper we present an initial effort to characterize the change of population activity in monkey prefrontal cortex (PFC) and hippocampus (HPC)...
Many studies of large-scale neural systems have emphasized the importance of communication through increased inter-region correlations ("functional connectivity") during task states relative to resting state. In contrast, local circuit studies have demonstrated that task states reduce correlations among local neural populations, likely enhancing th...
Understanding the function of different neuronal cell types is key to understanding brain function. However, cell type diversity is typically overlooked in electrophysiological studies in awake behaving animals. Here, we show that four functionally distinct cell classes can be robustly identified from extracellular recordings in several cortical re...
It remains challenging to relate EEG and MEG to underlying circuit processes and comparable experiments on both spatial scales are rare. To close this gap between invasive and non-invasive electrophysiology we developed and recorded human-comparable EEG in macaque monkeys during visual stimulation with colored dynamic random dot patterns. Furthermo...
Cognition involves using attended information, maintained in working memory (WM), to guide action. During a cognitive task, a correct response requires flexible, selective gating so that only the appropriate information flows from WM to downstream effectors that carry out the response. In this work, we used biophysically-detailed modeling to explor...
Many recent advances in artificial intelligence (AI) are rooted in visual neuroscience. However, ideas from more complicated paradigms like decision-making are less used. Although automated decision-making systems are ubiquitous (driverless cars, pilot support systems, medical diagnosis algorithms etc.), achieving human-level performance in decisio...
Oscillations of the brain’s local field potential (LFP) may coordinate neural ensembles and brain networks. It has been difficult to causally test this model or to translate its implications into treatments, because there are few reliable ways to alter LFP oscillations. We developed a closed-loop analog circuit to enhance brain oscillations by feed...
Working memory is the fundamental function by which we break free from reflexive input-output reactions to gain control over our own thoughts. It has two types of mechanisms: online maintenance of information and its volitional or executive control. Classic models proposed persistent spiking for maintenance but have not explicitly addressed executi...
In addition to the prefrontal cortex (PFC), the basal ganglia (BG) have been increasingly often reported to play a fundamental role in category learning, but the circuit mechanisms mediating their interaction remain to be explored. We developed a novel neurocomputational model of category learning that particularly addresses the BG–PFC interplay. W...
Working memory (WM) is characterized by the ability to maintain stable representations over time; however, neural activity associated with WM maintenance can be highly dynamic. We explore whether complex population coding dynamics during WM relate to the intrinsic temporal properties of single neurons in lateral prefrontal cortex (lPFC), the fronta...
