Dr. Michele Insanally

The Insanally Lab is hiring postdocs to study the neural basis of auditory perception and learning. We incorporate a wide range of techniques including behavioral paradigms, in vivo multi-region neural recordings, optogenetics, chemogenetics, fiber photometry, and novel computational methods. Our lab is super supportive, collaborative, and we take mentoring seriously! Located at Pitt, our lab is part of a large systems neuroscience community that includes CNBC and CMU. For inquiries, feel free to reach out to me here: mni@pitt.edu. To find out more about our work, visit Insanallylab.com

Organization of thalamic networks and mechanisms of dysfunction in schizophrenia and autism

Thalamic networks, at the core of thalamocortical and thalamosubcortical communications, underlie processes of perception, attention, memory, emotions, and the sleep-wake cycle, and are disrupted in mental disorders, including schizophrenia and autism. However, the underlying mechanisms of pathology are unknown. I will present novel evidence on key organizational principles, structural, and molecular features of thalamocortical networks, as well as critical thalamic pathway interactions that are likely affected in disorders. This data can facilitate modeling typical and abnormal brain function and can provide the foundation to understand heterogeneous disruption of these networks in sleep disorders, attention deficits, and cognitive and affective impairments in schizophrenia and autism, with important implications for the design of targeted therapeutic interventions

Neural Representations of Abstract Cognitive Maps in Prefrontal Cortex and Medial Temporal Lobe

Neural circuits underlying sleep structure and functions

Sleep is an active state critical for processing emotional memories encoded during waking in both humans and animals. There is a remarkable overlap between the brain structures and circuits active during sleep, particularly rapid eye-movement (REM) sleep, and the those encoding emotions. Accordingly, disruptions in sleep quality or quantity, including REM sleep, are often associated with, and precede the onset of, nearly all affective psychiatric and mood disorders. In this context, a major biomedical challenge is to better understand the underlying mechanisms of the relationship between (REM) sleep and emotion encoding to improve treatments for mental health. This lecture will summarize our investigation of the cellular and circuit mechanisms underlying sleep architecture, sleep oscillations, and local brain dynamics across sleep-wake states using electrophysiological recordings combined with single-cell calcium imaging or optogenetics. The presentation will detail the discovery of a 'somato-dendritic decoupling'in prefrontal cortex pyramidal neurons underlying REM sleep-dependent stabilization of optimal emotional memory traces. This decoupling reflects a tonic inhibition at the somas of pyramidal cells, occurring simultaneously with a selective disinhibition of their dendritic arbors selectively during REM sleep. Recent findings on REM sleep-dependent subcortical inputs and neuromodulation of this decoupling will be discussed in the context of synaptic plasticity and the optimization of emotional responses in the maintenance of mental health.

How do we sleep?

There is no consensus on if sleep is for the brain, body or both. But the difference in how we feel following disrupted sleep or having a good night of continuous sleep is striking. Understanding how and why we sleep will likely give insights into many aspects of health. In this talk I will outline our recent work on how the prefrontal cortex can signal to the hypothalamus to regulate sleep preparatory behaviours and sleep itself, and how other brain regions, including the ventral tegmental area, respond to psychosocial stress to induce beneficial sleep. I will also outline our work on examining the function of the glymphatic system, and whether clearance of molecules from the brain is enhanced during sleep or wakefulness.

Contribution of computational models of reinforcement learning to neurosciences/ computational modeling, reward, learning, decision-making, conditioning, navigation, dopamine, basal ganglia, prefrontal cortex, hippocampus

Decomposing motivation into value and salience

Humans and other animals approach reward and avoid punishment and pay attention to cues predicting these events. Such motivated behavior thus appears to be guided by value, which directs behavior towards or away from positively or negatively valenced outcomes. Moreover, it is facilitated by (top-down) salience, which enhances attention to behaviorally relevant learned cues predicting the occurrence of valenced outcomes. Using human neuroimaging, we recently separated value (ventral striatum, posterior ventromedial prefrontal cortex) from salience (anterior ventromedial cortex, occipital cortex) in the domain of liquid reward and punishment. Moreover, we investigated potential drivers of learned salience: the probability and uncertainty with which valenced and non-valenced outcomes occur. We find that the brain dissociates valenced from non-valenced probability and uncertainty, which indicates that reinforcement matters for the brain, in addition to information provided by probability and uncertainty alone, regardless of valence. Finally, we assessed learning signals (unsigned prediction errors) that may underpin the acquisition of salience. Particularly the insula appears to be central for this function, encoding a subjective salience prediction error, similarly at the time of positively and negatively valenced outcomes. However, it appears to employ domain-specific time constants, leading to stronger salience signals in the aversive than the appetitive domain at the time of cues. These findings explain why previous research associated the insula with both valence-independent salience processing and with preferential encoding of the aversive domain. More generally, the distinction of value and salience appears to provide a useful framework for capturing the neural basis of motivated behavior.

Prefrontal mechanisms involved in learning distractor-resistant working memory in a dual task

Working memory (WM) is a cognitive function that allows the short-term maintenance and manipulation of information when no longer accessible to the senses. It relies on temporarily storing stimulus features in the activity of neuronal populations. To preserve these dynamics from distraction it has been proposed that pre and post-distraction population activity decomposes into orthogonal subspaces. If orthogonalization is necessary to avoid WM distraction, it should emerge as performance in the task improves. We sought evidence of WM orthogonalization learning and the underlying mechanisms by analyzing calcium imaging data from the prelimbic (PrL) and anterior cingulate (ACC) cortices of mice as they learned to perform an olfactory dual task. The dual task combines an outer Delayed Paired-Association task (DPA) with an inner Go-NoGo task. We examined how neuronal activity reflected the process of protecting the DPA sample information against Go/NoGo distractors. As mice learned the task, we measured the overlap between the neural activity onto the low-dimensional subspaces that encode sample or distractor odors. Early in the training, pre-distraction activity overlapped with both sample and distractor subspaces. Later in the training, pre-distraction activity was strictly confined to the sample subspace, resulting in a more robust sample code. To gain mechanistic insight into how these low-dimensional WM representations evolve with learning we built a recurrent spiking network model of excitatory and inhibitory neurons with low-rank connections. The model links learning to (1) the orthogonalization of sample and distractor WM subspaces and (2) the orthogonalization of each subspace with irrelevant inputs. We validated (1) by measuring the angular distance between the sample and distractor subspaces through learning in the data. Prediction (2) was validated in PrL through the photoinhibition of ACC to PrL inputs, which induced early-training neural dynamics in well-trained animals. In the model, learning drives the network from a double-well attractor toward a more continuous ring attractor regime. We tested signatures for this dynamical evolution in the experimental data by estimating the energy landscape of the dynamics on a one-dimensional ring. In sum, our study defines network dynamics underlying the process of learning to shield WM representations from distracting tasks.

A recurrent network model of planning predicts hippocampal replay and human behavior

When interacting with complex environments, humans can rapidly adapt their behavior to changes in task or context. To facilitate this adaptation, we often spend substantial periods of time contemplating possible futures before acting. For such planning to be rational, the benefits of planning to future behavior must at least compensate for the time spent thinking. Here we capture these features of human behavior by developing a neural network model where not only actions, but also planning, are controlled by prefrontal cortex. This model consists of a meta-reinforcement learning agent augmented with the ability to plan by sampling imagined action sequences drawn from its own policy, which we refer to as `rollouts'. Our results demonstrate that this agent learns to plan when planning is beneficial, explaining the empirical variability in human thinking times. Additionally, the patterns of policy rollouts employed by the artificial agent closely resemble patterns of rodent hippocampal replays recently recorded in a spatial navigation task, in terms of both their spatial statistics and their relationship to subsequent behavior. Our work provides a new theory of how the brain could implement planning through prefrontal-hippocampal interactions, where hippocampal replays are triggered by -- and in turn adaptively affect -- prefrontal dynamics.

A recurrent network model of planning explains hippocampal replay and human behavior

When interacting with complex environments, humans can rapidly adapt their behavior to changes in task or context. To facilitate this adaptation, we often spend substantial periods of time contemplating possible futures before acting. For such planning to be rational, the benefits of planning to future behavior must at least compensate for the time spent thinking. Here we capture these features of human behavior by developing a neural network model where not only actions, but also planning, are controlled by prefrontal cortex. This model consists of a meta-reinforcement learning agent augmented with the ability to plan by sampling imagined action sequences drawn from its own policy, which we refer to as 'rollouts'. Our results demonstrate that this agent learns to plan when planning is beneficial, explaining the empirical variability in human thinking times. Additionally, the patterns of policy rollouts employed by the artificial agent closely resemble patterns of rodent hippocampal replays recently recorded in a spatial navigation task, in terms of both their spatial statistics and their relationship to subsequent behavior. Our work provides a new theory of how the brain could implement planning through prefrontal-hippocampal interactions, where hippocampal replays are triggered by - and in turn adaptively affect - prefrontal dynamics.

Distinct contributions of different anterior frontal regions to rule-guided decision-making in primates: complementary evidence from lesions, electrophysiology, and neurostimulation

Different prefrontal areas contribute in distinctly different ways to rule-guided behaviour in the context of a Wisconsin Card Sorting Test (WCST) analog for macaques. For example, causal evidence from circumscribed lesions in NHPs reveals that dorsolateral prefrontal cortex (dlPFC) is necessary to maintain a reinforced abstract rule in working memory, orbitofrontal cortex (OFC) is needed to rapidly update representations of rule value, and the anterior cingulate cortex (ACC) plays a key role in cognitive control and integrating information for correct and incorrect trials over recent outcomes. Moreover, recent lesion studies of frontopolar cortex (FPC) suggest it contributes to representing the relative value of unchosen alternatives, including rules. Yet we do not understand how these functional specializations relate to intrinsic neuronal activities nor the extent to which these neuronal activities differ between different prefrontal regions. After reviewing the aforementioned causal evidence I will present our new data from studies using multi-area multi-electrode recording techniques in NHPs to simultaneously record from four different prefrontal regions implicated in rule-guided behaviour. Multi-electrode micro-arrays (‘Utah arrays’) were chronically implanted in dlPFC, vlPFC, OFC, and FPC of two macaques, allowing us to simultaneously record single and multiunit activity, and local field potential (LFP), from all regions while the monkey performs the WCST analog. Rule-related neuronal activity was widespread in all areas recorded but it differed in degree and in timing between different areas. I will also present preliminary results from decoding analyses applied to rule-related neuronal activities both from individual clusters and also from population measures. These results confirm and help quantify dynamic task-related activities that differ between prefrontal regions. We also found task-related modulation of LFPs within beta and gamma bands in FPC. By combining this correlational recording methods with trial-specific causal interventions (electrical microstimulation) to FPC we could significantly enhance and impair animals performance in distinct task epochs in functionally relevant ways, further consistent with an emerging picture of regional functional specialization within a distributed framework of interacting and interconnected cortical regions.

Dopamine and cellular mechanisms of cognitive control in primate prefrontal cortex

Working memory tasks for functional mapping of the prefrontal cortex in common marmosets

The medial prefrontal cortex replays generalized sequences

Whilst spatial navigation is a function ascribed to the hippocampus, flexibly adapting to a change in rule depends on the medial prefrontal cortex (mPFC). Single-units were recorded from the hippocampus and mPFC of rats shifting between a spatially- and cue-guided rule on a plus-maze. The mPFC population coded for the relative position between start and goal arm. During awake immobility periods, the mPFC replayed organized sequences of generalized positions which positively correlated with rule-switching performance. Conversely, hippocampal replay negatively correlated with performance and occurred independently of mPFC replay. Sequential replay in the hippocampus and mPFC may thus serve different functions.

Extracting computational mechanisms from neural data using low-rank RNNs

An influential theory in systems neuroscience suggests that brain function can be understood through low-dimensional dynamics [Vyas et al 2020]. However, a challenge in this framework is that a single computational task may involve a range of dynamic processes. To understand which processes are at play in the brain, it is important to use data on neural activity to constrain models. In this study, we present a method for extracting low-dimensional dynamics from data using low-rank recurrent neural networks (lrRNNs), a highly expressive and understandable type of model [Mastrogiuseppe & Ostojic 2018, Dubreuil, Valente et al. 2022]. We first test our approach using synthetic data created from full-rank RNNs that have been trained on various brain tasks. We find that lrRNNs fitted to neural activity allow us to identify the collective computational processes and make new predictions for inactivations in the original RNNs. We then apply our method to data recorded from the prefrontal cortex of primates during a context-dependent decision-making task. Our approach enables us to assign computational roles to the different latent variables and provides a mechanistic model of the recorded dynamics, which can be used to perform in silico experiments like inactivations and provide testable predictions.

Prefrontal top-down projections control context-dependent strategy selection

The rules governing behavior often vary with behavioral contexts. As a result, an action rewarded in one context may be discouraged in another. Animals and humans are capable of switching between behavioral strategies under different contexts and acting adaptively according to the variable rules, a flexibility that is thought to be mediated by the prefrontal cortex (PFC). However, how the PFC orchestrates the context-dependent switch of strategies remains unclear. Here we show that pathway-specific projection neurons in the medial PFC (mPFC) differentially contribute to context-instructed strategy selection. In mice trained in a decision-making task in which a previously established rule and a newly learned rule are associated with distinct contexts, the activity of mPFC neurons projecting to the dorsomedial striatum (mPFC-DMS) encodes the contexts and further represents decision strategies conforming to the old and new rules. Moreover, mPFC-DMS neuron activity is required for the context-instructed strategy selection. In contrast, the activity of mPFC neurons projecting to the ventral midline thalamus (mPFC-VMT) does not discriminate between the contexts, and represents the old rule even if mice have adopted the new one. Furthermore, these neurons act to prevent the strategy switch under the new rule. Our results suggest that mPFC-DMS neurons promote flexible strategy selection guided by contexts, whereas mPFC-VMT neurons favor fixed strategy selection by preserving old rules.

Neural Dynamics of Cognitive Control

Cognitive control guides behavior by controlling what, where, and how information is represented in the brain. Perhaps the most well-studied form of cognitive control has been ‘attention’, which controls how external sensory stimuli are represented in the brain. In contrast, the neural mechanisms controlling the selection of representations held ‘in mind’, in working memory, are unknown. In this talk, I will present evidence that the prefrontal cortex controls working memory by selectively enhancing and transforming the contents of working memory. In particular, I will show how the neural representation of the content of working memory changes over time, moving between different ‘subspaces’ of the neural population. These dynamics may play a critical role in controlling what and how neural representations are acted upon.

Neural Coding for Flexible Behavior in Prefrontal Cortex

Optimal information loading into working memory in prefrontal cortex

Working memory involves the short-term maintenance of information and is critical in many tasks. The neural circuit dynamics underlying working memory remain poorly understood, with different aspects of prefrontal cortical (PFC) responses explained by different putative mechanisms. By mathematical analysis, numerical simulations, and using recordings from monkey PFC, we investigate a critical but hitherto ignored aspect of working memory dynamics: information loading. We find that, contrary to common assumptions, optimal information loading involves inputs that are largely orthogonal, rather than similar, to the persistent activities observed during memory maintenance. Using a novel, theoretically principled metric, we show that PFC exhibits the hallmarks of optimal information loading and we find that such dynamics emerge naturally as a dynamical strategy in task-optimized recurrent neural networks. Our theory unifies previous, seemingly conflicting theories of memory maintenance based on attractor or purely sequential dynamics, and reveals a normative principle underlying the widely observed phenomenon of dynamic coding in PFC.

Neural circuits of visuospatial working memory

One elementary brain function that underlies many of our cognitive behaviors is the ability to maintain parametric information briefly in mind, in the time scale of seconds, to span delays between sensory information and actions. This component of working memory is fragile and quickly degrades with delay length. Under the assumption that behavioral delay-dependencies mark core functions of the working memory system, our goal is to find a neural circuit model that represents their neural mechanisms and apply it to research on working memory deficits in neuropsychiatric disorders. We have constrained computational models of spatial working memory with delay-dependent behavioral effects and with neural recordings in the prefrontal cortex during visuospatial working memory. I will show that a simple bump attractor model with weak inhomogeneities and short-term plasticity mechanisms can link neural data with fine-grained behavioral output in a trial-by-trial basis and account for the main delay-dependent limitations of working memory: precision, cardinal repulsion biases and serial dependence. I will finally present data from participants with neuropsychiatric disorders that suggest that serial dependence in working memory is specifically altered, and I will use the model to infer the possible neural mechanisms affected.

Multimodal investigation of the associations between sleep and Alzheimer's disease neuropathology in healthy individuals

Alterations in sleep are hallmarks of the ageing process and emerges as risk factors for Alzheimer’s disease (AD). While the fine-tuned coalescence of sleep microstructure elements may influence age-related cognitive trajectories, its association with AD-related processes is not fully established. We investigated whether sleep arousals and the coupling of spindles and slow waves, key elements of sleep microstructure, are associated with early amyloid-beta (Aβ) brain burden, hallmark of AD neuropathology, and cognitive change at 2 years in 100 late-midlife healthy individuals. We first found that arousals interrupting sleep continuity were positively linked to Aβ burden, while, by contrast, the more prevalent arousals upholding sleep continuity were associated with lower Aβ burden and better cognition. We further found that young-like co-occurrence of spindles and slow-depolarisation slow waves is associated to lower burden of Aβ over the medial prefrontal cortex and is predictive of memory decline at 2-year follow-up. We provide empirical evidence that arousals are diverse and differently associated with early AD-related neuropathology and cognition. We further show the altered coupling of sleep microstructure elements that are key to its mnesic functions may contribute to poorer brain and cognitive trajectories. The presentation will end with preliminary data show that activity of the locus coeruleus, essential to sleep and showing some of the earliest signs of AD-related pathological processes, is associated with sleep quality. These preliminary findings are the first of a project ailed at link sleep and AD through the locus coeruleus.

Geometry of sequence working memory in macaque prefrontal cortex

How the brain stores a sequence in memory remains largely unknown. We investigated the neural code underlying sequence working memory using two-photon calcium imaging to record thousands of neurons in the prefrontal cortex of macaque monkeys memorizing and then reproducing a sequence of locations after a delay. We discovered a regular geometrical organization: The high-dimensional neural state space during the delay could be decomposed into a sum of low-dimensional subspaces, each storing the spatial location at a given ordinal rank, which could be generalized to novel sequences and explain monkey behavior. The rank subspaces were distributed across large overlapping neural groups, and the integration of ordinal and spatial information occurred at the collective level rather than within single neurons. Thus, a simple representational geometry underlies sequence working memory.

Astroglial modulation of the antidepressant action of deep brain and bright light stimulation

Even if major depression is now the most common of psychiatric disorders, successful antidepressant treatments are still difficult to achieve. Therefore, a better understanding of the mechanisms of action of current antidepressant treatments is needed to ultimately identify new targets and enhance beneficial effects. Given the intimate relationships between astrocytes and neurons at synapses and the ability of astrocytes to "sense" neuronal communication and release gliotransmitters, an attractive hypothesis is emerging stating that the effects of antidepressants on brain function could be, at least in part, modulated by direct influences of astrocytes on neuronal networks. We will present two preclinical studies revealing a permissive role of glia in the antidepressant response: i) Control of the antidepressant-like effects of rat prefrontal cortex Deep Brain Stimulation (DBS) by astroglia, ii) Modulation of antidepressant efficacy of Bright Light Stimulation (BLS) by lateral habenula astroglia. Therefore, it is proposed that an unaltered neuronal-glial system constitutes a major prerequisite to optimize antidepressant efficacy of DBS or BLS. Collectively, these results pave also the way to the development of safer and more effective antidepressant strategies.

Dissecting the neural processes supporting perceptual learning

The brain and its inherent functions can be modified by various forms of learning. Learning-induced changes are seen even in basic perceptual functions. In particular, repeated training in a perceptual task can lead to a significant improvement in the trained task—a phenomenon known as perceptual learning. There has been a long-standing debate about the mechanisms of perceptual learning. In this talk, I will present results from our series of electrophysiological studies. These studies have consistently shown that perceptual learning is mediated by concerted changes in both perceptual and cognitive processes, resulting in improved sensory representation, enhanced top-down influences, and refined readout process.

Orbitofrontal cortex and the integrative approach to functional neuroanatomy

The project of functional neuroanatomy typically considers single brain areas as the core functional unit of the brain. Functional neuroanatomists typically use specialized tasks that are designed to isolate hypothesized functions from other cognitive processes. Our lab takes a broader view; specifically, we consider brain regions as parts of larger circuits and we take cognitive processes as part of more complex behavioral repertoires. In my talk, I will discuss the ramifications of this perspective for thinking about the role of the orbitofrontal cortex. I will discuss results of recent experiments from my lab that tackle the question of OFC function within the context of larger brain networks and in freely moving foraging tasks. I will argue that this perspective challenges conventional accounts of the role of OFC and invites new ones. I will conclude by speculating on implications for the practice of functional neuroanatomy.

From plans to outcomes: continuous representations of actions in primate prefrontal cortex

Reasoning Ability: Neural Mechanisms, Development, and Plasticity

Relational thinking, or the process of identifying and integrating relations between mental representations, is regularly invoked during reasoning. This mental capacity enables us to draw higher-order abstractions and generalize across situations and contexts, and we have argued that it should be included in the pantheon of executive functions. In this talk, I will briefly review our lab's work characterizing the roles of lateral prefrontal and parietal regions in relational thinking. I will then discuss structural and functional predictors of individual differences and developmental changes in reasoning.

Dissecting the neural circuits underlying prefrontal regulation of reward and threat responsivity in a primate

Gaining insight into the overlapping neural circuits that regulate positive and negative emotion is an important step towards understanding the heterogeneity in the aetiology of anxiety and depression and developing new treatment targets. Determining the core contributions of the functionally heterogenous prefrontal cortex to these circuits is especially illuminating given its marked dysregulation in affective disorders. This presentation will review a series of studies in a new world monkey, the common marmoset, employing pathway-specific chemogenetics, neuroimaging, neuropharmacology and behavioural and cardiovascular analysis to dissect out prefrontal involvement in the regulation of both positive and negative emotion. Highlights will include the profound shift of sensitivity away from reward and towards threat induced by localised activations within distinct regions of vmPFC, namely areas 25 and 14 as well as the opposing contributions of this region, compared to orbitofrontal and dorsolateral prefrontal cortex, in the overall responsivity to threat. Ongoing follow-up studies are identifying the distinct downstream pathways that mediate some of these effects as well as their differential sensitivity to rapidly acting anti-depressants.

From single cell to population coding during defensive behaviors in prefrontal circuits

Coping with threatening situations requires both identifying stimuli predicting danger and selecting adaptive behavioral responses in order to survive. The dorso medial prefrontal cortex (dmPFC) is a critical structure involved in the regulation of threat-related behaviour, yet it is still largely unclear how threat-predicting stimuli and defensive behaviours are associated within prefrontal networks in order to successfully drive adaptive responses. Over the past years, we used a combination we used a combination of extracellular recordings, neuronal decoding approaches, and state of the art optogenetic manipulations to identify key neuronal elements and mechanisms controlling defensive fear responses. I will present an overview of our recent work ranging from analyses of dedicated neuronal types and oscillatory and synchronization mechanisms to artificial intelligence approaches used to decode the activity or large population of neurons. Ultimately these analyses allowed the identification of high dimensional representations of defensive behavior unfolding within prefrontal networks.

The pervasive role of visuospatial coding

Historically, retinotopic organisation (the spatial mapping of the retina across the cortical surface) was considered the purview of early regions of visual cortex (V1-V4) only and that anterior, more cognitively involved regions abstracted this information away. The contemporary view is quite different. Here, with Advancing technologies and analysis methods, we see that retinotopic information is not simply thrown away by these regions but rather is maintained to the potential benefit of our broader cognition. This maintenance of visuospatial coding extends not only through visual cortex, but is present in parietal, frontal, medial and subcortical structures involved with coordinating-movements, mind-wandering and even memory. In this talk, I will outline some of the key empirical findings from my own work and the work of others that shaped this contemporary perspective.

Frontal circuit specialisations for information search and decision making

During primate evolution, prefrontal cortex (PFC) expanded substantially relative to other cortical areas. The expansion of PFC circuits likely supported the increased cognitive abilities of humans and anthropoids to sample information about their environment, evaluate that information, plan, and decide between different courses of action. What quantities do these circuits compute as information is being sampled towards and a decision is being made? And how can they be related to anatomical specialisations within and across PFC? To address this, we recorded PFC activity during value-based decision making using single unit recording in non-human primates and magnetoencephalography in humans. At a macrocircuit level, we found that value correlates differ substantially across PFC subregions. They are heavily shaped by each subregion’s anatomical connections and by the decision-maker’s current locus of attention. At a microcircuit level, we found that the temporal evolution of value correlates can be predicted using cortical recurrent network models that temporally integrate incoming decision evidence. These models reflect the fact that PFC circuits are highly recurrent in nature and have synaptic properties that support persistent activity across temporally extended cognitive tasks. Our findings build upon recent work describing economic decision making as a process of attention-weighted evidence integration across time.

Stress deceleration theory: chronic adolescent stress exposure results in decelerated neurobehavioral maturation

Normative development in adolescence indicates that the prefrontal cortex is still under development thereby unable to exert efficient top-down inhibitory control on subcortical regions such as the basolateral amygdala and the nucleus accumbens. This imbalance in the developmental trajectory between cortical and subcortical regions is implicated in expression of the prototypical impulsive, compulsive, reward seeking and risk-taking adolescent behavior. Here we demonstrate that a chronic mild unpredictable stress procedure during adolescence in male Wistar rats arrests the normal behavioral maturation such that they continue to express adolescent-like impulsive, hyperactive, and compulsive behaviors into late adulthood. This arrest in behavioral maturation is associated with the hypoexcitability of prelimbic cortex (PLC) pyramidal neurons and reduced PLC-mediated synaptic glutamatergic control of BLA and nucleus accumbens core (NAcC) neurons that lasts late into adulthood. At the same time stress exposure in adolescence results in the hyperexcitability of the BLA pyramidal neurons sending stronger glutamatergic projections to the NAcC. Chemogenetic reversal of the PLC hypoexcitability decreased compulsivity and improved the expression of goal-directed behavior in rats exposed to stress during adolescence, suggesting a causal role for PLC hypoexcitability in this stress-induced arrested behavioral development. (https://www.biorxiv.org/content/10.1101/2021.11.21.469381v1.abstract)

A Network for Computing Value Equilibrium in the Human Medial Prefrontal Corte

Humans and other animals make decisions in order to satisfy their goals. However, it remains unknown how neural circuits compute which of multiple possible goals should be pursued (e.g., when balancing hunger and thirst) and how to combine these signals with estimates of available reward alternatives. Here, humans undergoing fMRI accumulated two distinct assets over a sequence of trials. Financial outcomes depended on the minimum cumulate of either asset, creating a need to maintain “value equilibrium” by redressing any imbalance among the assets. Blood-oxygen-level-dependent (BOLD) signals in the rostral anterior cingulate cortex (rACC) tracked the level of imbalance among goals, whereas the ventromedial prefrontal cortex (vmPFC) signaled the level of redress incurred by a choice rather than the overall amount received. These results suggest that a network of medial frontal brain regions compute a value signal that maintains value equilibrium among internal goals.

NMC4 Short Talk: Two-Photon Imaging of Norepinephrine in the Prefrontal Cortex Shows that Norepinephrine Structures Cell Firing Through Local Release

Norepinephrine (NE) is a neuromodulator that is released from projections of the locus coeruleus via extra-synaptic vesicle exocytosis. Tonic fluctuations in NE are involved in brain states, such as sleep, arousal, and attention. Previously, NE in the PFC was thought to be a homogenous field created by bulk release, but it remains unknown whether phasic (fast, short-term) fluctuations in NE can produce a spatially heterogeneous field, which could then structure cell firing at a fine spatial scale. To understand how spatiotemporal dynamics of norepinephrine (NE) release in the prefrontal cortex affect neuronal firing, we performed a novel in-vivo two-photon imaging experiment in layer ⅔ of the prefrontal cortex using a green fluorescent NE sensor and a red fluorescent Ca2+ sensor, which allowed us to simultaneously observe fine-scale neuronal and NE dynamics in the form of spatially localized fluorescence time series. Using generalized linear modeling, we found that the local NE field differs from the global NE field in transient periods of decorrelation, which are influenced by proximal NE release events. We used optical flow and pattern analysis to show that release and reuptake events can occur at the same location but at different times, and differential recruitment of release and reuptake sites over time is a potential mechanism for creating a heterogeneous NE field. Our generalized linear models predicting cellular dynamics show that the heterogeneous local NE field, and not the global field, drives cell firing dynamics. These results point to the importance of local, small-scale, phasic NE fluctuations for structuring cell firing. Prior research suggests that these phasic NE fluctuations in the PFC may play a role in attentional shifts, orienting to sensory stimuli in the environment, and in the selective gain of priority representations during stress (Mather, Clewett et al. 2016) (Aston-Jones and Bloom 1981).

NMC4 Short Talk: Different hypotheses on the role of the PFC in solving simple cognitive tasks

Low-dimensional population dynamics can be observed in neural activity recorded from the prefrontal cortex (PFC) of subjects performing simple cognitive tasks. Many studies have shown that recurrent neural networks (RNNs) trained on the same tasks can reproduce qualitatively these state space trajectories, and have used them as models of how neuronal dynamics implement task computations. The PFC is also viewed as a conductor that organizes the communication between cortical areas and provides contextual information. It is then not clear what is its role in solving simple cognitive tasks. Do the low-dimensional trajectories observed in the PFC really correspond to the computations that it performs? Or do they indirectly reflect the computations occurring within the cortical areas projecting to the PFC? To address these questions, we modelled cortical areas with a modular RNN and equipped it with a PFC-like cognitive system. When trained on cognitive tasks, this multi-system brain model can reproduce the low-dimensional population responses observed in neuronal activity as well as classical RNNs. Qualitatively different mechanisms can emerge from the training process when varying some details of the architecture such as the time constants. In particular, there is one class of models where it is the dynamics of the cognitive system that is implementing the task computations, and another where the cognitive system is only necessary to provide contextual information about the task rule as task performance is not impaired when preventing the system from accessing the task inputs. These constitute two different hypotheses about the causal role of the PFC in solving simple cognitive tasks, which could motivate further experiments on the brain.

NMC4 Short Talk: Stretching and squeezing of neuronal log firing rate distribution by psychedelic and intrinsic brain state transitions

How psychedelic drugs change the activity of cortical neuronal populations is not well understood. It is also not clear which changes are specific to transition into the psychedelic brain state and which are shared with other brain state transitions. Here, we used Neuropixels probes to record from large populations of neurons in prefrontal cortex of mice given the psychedelic drug TCB-2. The primary effect of drug ingestion was stretching of the distribution of log firing rates of the recorded population. This phenomenon was previously observed across transitions between sleep and wakefulness, which prompted us to examine how common it is. We found that modulation of the width of the log-rate distribution of a neuronal population occurred in multiple areas of the cortex and in the hippocampus even in awake drug-free mice, driven by intrinsic fluctuations in their arousal level. Arousal, however, did not explain the stretching of the log-rate distribution by TCB-2. In both psychedelic and intrinsically occurring brain state transitions, the stretching or squeezing of the log-rate distribution of an entire neuronal population were the result of a more close overlap between log-rate distributions of the upregulated and downregulated subpopulations in one brain state compared to the other brain state. Often, we also observed that the log-rate distribution of the downregulated subpopulation was stretched, whereas the log-rate distribution of the upregulated subpopulation was squeezed. In both subpopulations, the stretching and squeezing were a signature of a greater relative impact of the brain state transition on the rates of the slow-firing neurons. These findings reveal a generic pattern of reorganisation of neuronal firing rates by different kinds of brain state transitions.

The role of the primate prefrontal cortex in inferring the state of the world and predicting change

In an ever-changing environment, uncertainty is omnipresent. To deal with this, organisms have evolved mechanisms that allow them to take advantage of environmental regularities in order to make decisions robustly and adjust their behavior efficiently, thus maximizing their chances of survival. In this talk, I will present behavioral evidence that animals perform model-based state inference to predict environmental state changes and adjust their behavior rapidly, rather than slowly updating choice values. This model-based inference process can be described using Bayesian change-point models. Furthermore, I will show that neural populations in the prefrontal cortex accurately predict behavioral switches, and that the activity of these populations is associated with Bayesian estimates. In addition, we will see that learning leads to the emergence of a high-dimensional representational subspace that can be reused when the animals re-learn a previously learned set of action-value associations. Altogether, these findings highlight the role of the PFC in representing a belief about the current state of the world.

Rule learning representation in the fronto-parietal network

We must constantly adapt the rules we use to guide our attention. To understand how the brain learns these rules, we designed a novel task that required monkeys to learn which color is the most rewarded at a given time (the current rule). However, just as in real life, the monkey was never explicitly told the rule. Instead, they had to learn it through trial and error by choosing a color, receiving feedback (amount of reward), and then updating their internal rule. After the monkeys reached a behavioral criterion, the rule changed. This change was not cued but could be inferred based on reward feedback. Behavioral modeling found monkeys used rewards to learn the rules. After the rule changed, animals adopted one of two strategies. If the change was small, reflected in a small reward prediction error, the animals continuously updated their rule. However, for large changes, monkeys ‘reset’ their belief about the rule and re-learned the rule from scratch. To understand the neural correlates of learning new rules, we recorded neurons simultaneously from the prefrontal and parietal cortex. We found that the strength of the rule representation increased with the certainty about the current rule, and that the certainty about the rule was represented both implicitly and explicitly in the population.

The Challenge and Opportunities of Mapping Cortical Layer Activity and Connectivity with fMRI

In this talk I outline the technical challenges and current solutions to layer fMRI. Specifically, I describe our acquisition strategies for maximizing resolution, spatial coverage, time efficiency as well as, perhaps most importantly, vascular specificity. Novel applications from our group, including mapping feedforward and feedback connections to M1 during task and sensory input modulation and S1 during a sensory prediction task are be shown. Layer specific activity in dorsal lateral prefrontal cortex during a working memory task is also demonstrated. Additionally, I’ll show preliminary work on mapping whole brain layer-specific resting state connectivity and hierarchy.

Using extra-hippocampal cognitive maps for goal-directed spatial navigation

Goal-directed navigation requires precise estimates of spatial relationships between current position and future goal, as well as planning of an associated route or action. While neurons in the hippocampal formation can represent the animal’s position and nearby trajectories, their role in determining the animal’s destination or action has been questioned. We thus hypothesize that brain regions outside the hippocampal formation may play complementary roles in navigation, particularly for guiding goal-directed behaviours based on the brain’s internal cognitive map. In this seminar, I will first describe a subpopulation of neurons in the retrosplenial cortex (RSC) that increase their firing when the animal approaches environmental boundaries, such as walls or edges. This boundary coding is independent of direct visual or tactile sensation but instead depends on inputs from the medial entorhinal cortex (MEC) that contains spatial tuning cells, such as grid cells or border cells. However, unlike MEC border cells, we found that RSC border cells encode environmental boundaries in a self-centred egocentric coordinate frame, which may allow an animal for efficient avoidance from approaching walls or edges during navigation. I will then discuss whether the brain can possess a precise estimate of remote target location during active environmental exploration. Such a spatial code has not been described in the hippocampal formation. However, we found that neurons in the rat orbitofrontal cortex (OFC) form spatial representations that persistently point to the animal’s subsequent goal destination throughout navigation. This destination coding emerges before navigation onset without direct sensory access to a distal goal, and are maintained via destination-specific neural ensemble dynamics. These findings together suggest key roles for extra-hippocampal regions in spatial navigation, enabling animals to choose appropriate actions toward a desired destination by avoiding possible dangers.

Dynamical population coding during defensive behaviours in prefrontal circuits

Coping with threatening situations requires both identifying stimuli predicting danger and selecting adaptive behavioral responses in order to survive. The dorso medial prefrontal cortex (dmPFC) is a critical structure involved in the regulation of threat-related behaviour, yet it is still largely unclear how threat-predicting stimuli and defensive behaviours are associated within prefrontal networks in order to successfully drive adaptive responses. To address these questions, we used a combination of extracellular recordings, neuronal decoding approaches, and optogenetic manipulations to show that threat representations and the initiation of avoidance behaviour are dynamically encoded in the overall population activity of dmPFC neurons. These data indicate that although dmPFC population activity at stimulus onset encodes sustained threat representations and discriminates threat- from non-threat cues, it does not predict action outcome. In contrast, transient dmPFC population activity prior to action initiation reliably predicts avoided from non-avoided trials. Accordingly, optogenetic inhibition of prefrontal activity critically constrained the selection of adaptive defensive responses in a time-dependent manner. These results reveal that the adaptive selection of active fear responses relies on a dynamic process of information linking threats with defensive actions unfolding within prefrontal networks.

Higher cognitive resources for efficient learning

A central issue in reinforcement learning (RL) is the ‘curse-of-dimensionality’, arising when the degrees-of-freedom are much larger than the number of training samples. In such circumstances, the learning process becomes too slow to be plausible. In the brain, higher cognitive functions (such as abstraction or metacognition) may be part of the solution by generating low dimensional representations on which RL can operate. In this talk I will discuss a series of studies in which we used functional magnetic resonance imaging (fMRI) and computational modeling to investigate the neuro-computational basis of efficient RL. We found that people can learn remarkably complex task structures non-consciously, but also that - intriguingly - metacognition appears tightly coupled to this learning ability. Furthermore, when people use an explicit (conscious) policy to select relevant information, learning is accelerated by abstractions. At the neural level, prefrontal cortex subregions are differentially involved in separate aspects of learning: dorsolateral prefrontal cortex pairs with metacognitive processes, while ventromedial prefrontal cortex with valuation and abstraction. I will discuss the implications of these findings, in particular new questions on the function of metacognition in adaptive behavior and the link with abstraction.

Frontal circuit specialisations for decision making

During primate evolution, prefrontal cortex (PFC) expanded substantially relative to other cortical areas. The expansion of PFC circuits likely supported the increased cognitive abilities of humans and anthropoids to plan, evaluate, and decide between different courses of action. But what do these circuits compute as a decision is being made, and how can they be related to anatomical specialisations within and across PFC? To address this, we recorded PFC activity during value-based decision making using single unit recording in non-human primates and magnetoencephalography in humans. At a macrocircuit level, we found that value correlates differ substantially across PFC subregions. They are heavily shaped by each subregion’s anatomical connections and by the decision-maker’s current locus of attention. At a microcircuit level, we found that the temporal evolution of value correlates can be predicted using cortical recurrent network models that temporally integrate incoming decision evidence. These models reflect the fact that PFC circuits are highly recurrent in nature and have synaptic properties that support persistent activity across temporally extended cognitive tasks. Our findings build upon recent work describing economic decision making as a process of attention-weighted evidence integration across time.

Meta-analytic evidence of differential prefrontal and early sensory cortex activity during non-social sensory perception in autism

To date, neuroimaging research has had a limited focus on non-social features of autism. As a result, neurobiological explanations for atypical sensory perception in autism are lacking. To address this, we quantitively condensed findings from the non-social autism fMRI literature in line with the current best practices for neuroimaging meta-analyses. Using activation likelihood estimation (ALE), we conducted a series of robust meta-analyses across 83 experiments from 52 fMRI studies investigating differences between autistic (n = 891) and typical (n = 967) participants. We found that typical controls, compared to autistic people, show greater activity in the prefrontal cortex (BA9, BA10) during perception tasks. More refined analyses revealed that, when compared to typical controls, autistic people show greater recruitment of the extrastriate V2 cortex (BA18) during visual processing. Taken together, these findings contribute to our understanding of current theories of autistic perception, and highlight some of the challenges of cognitive neuroscience research in autism.

The neuroscience of color and what makes primates special

Among mammals, excellent color vision has evolved only in certain non-human primates. And yet, color is often assumed to be just a low-level stimulus feature with a modest role in encoding and recognizing objects. The rationale for this dogma is compelling: object recognition is excellent in grayscale images (consider black-and-white movies, where faces, places, objects, and story are readily apparent). In my talk I will discuss experiments in which we used color as a tool to uncover an organizational plan in inferior temporal cortex (parallel, multistage processing for places, faces, colors, and objects) and a visual-stimulus functional representation in prefrontal cortex (PFC). The discovery of an extensive network of color-biased domains within IT and PFC, regions implicated in high-level object vision and executive functions, compels a re-evaluation of the role of color in behavior. I will discuss behavioral studies prompted by the neurobiology that uncover a universal principle for color categorization across languages, the first systematic study of the color statistics of objects and a chromatic mechanism by which the brain may compute animacy, and a surprising paradoxical impact of memory on face color. Taken together, my talk will put forward the argument that color is not primarily for object recognition, but rather for the assessment of the likely behavioral relevance, or meaning, of the stuff we see.

Feed-forward inhibition in Dentate Gyrus-CA3 instructs time-dependent re-organization of memory ensembles in prefrontal cortex

Abstraction and Inference in the Prefrontal Hippocampal Circuitry

The cellular representations and computations that allow rodents to navigate in space have been described with beautiful precision. In this talk, I will show that some of these same computations can be found in humans doing tasks that appear very different from spatial navigation. I will describe some theory that allows us to think about spatial and non-spatial problems in the same framework, and I will try to use this theory to give a new perspective on the beautiful spatial computations that inspired it. The overall goal of this work is to find a framework where we can talk about complicated non-spatial inference problems with the same precision that is only currently available in space.

Values Encoded in Orbitofrontal Cortex Are Causally Linked to Economic Choices

Classic economists proposed that economic choices rely on the computation and comparison of subjective values. This hypothesis continues to inform economic theory and experimental research, but behavioral measures are ultimately not sufficient to prove the proposal. Consistent with the hypothesis, when agents make choices, neurons in the orbitofrontal cortex (OFC) encode the subjective value of offered and chosen goods. Moreover, neuronal activity in this area suggests the formation of a decision. However, it is unclear whether these neural processes are causally related to choices. More generally, the evidence linking choices to value signals in the brain remains correlational. In my talk, I will present recent results showing that neuronal activity in OFC are causal to economic choices.

Neuronal encoding of drug choices and preference in the orbitofrontal cortex

Human neuroimaging research has consistently shown that drug addiction is associated with structural and functional changes within the orbitofrontal cortex (OFC). In view of the important role of the OFC in value-based decision-making, these changes have been hypothesised to bias choice towards drug use despite and at the expense of other competing pursuits, thereby explaining drug addiction. Here I will present in vivo recording data in the OFC supporting this hypothesis in a choice-based model of addiction where rats could choose between two actions, one rewarded by a drug (cocaine or heroin), the other by a nondrug alternative (saccharin).

Residual population dynamics as a window into neural computation

Neural activity in frontal and motor cortices can be considered to be the manifestation of a dynamical system implemented by large neural populations in recurrently connected networks. The computations emerging from such population-level dynamics reflect the interaction between external inputs into a network and its internal, recurrent dynamics. Isolating these two contributions in experimentally recorded neural activity, however, is challenging, limiting the resulting insights into neural computations. I will present an approach to addressing this challenge based on response residuals, i.e. variability in the population trajectory across repetitions of the same task condition. A complete characterization of residual dynamics is well-suited to systematically compare computations across brain areas and tasks, and leads to quantitative predictions about the consequences of small, arbitrary causal perturbations.

From oscillations to laminar responses - characterising the neural circuitry of autobiographical memories

Autobiographical memories are the ghosts of our past. Through them we visit places long departed, see faces once familiar, and hear voices now silent. These, often decades-old, personal experiences can be recalled on a whim or come unbidden into our everyday consciousness. Autobiographical memories are crucial to cognition because they facilitate almost everything we do, endow us with a sense of self and underwrite our capacity for autonomy. They are often compromised by common neurological and psychiatric pathologies with devastating effects. Despite autobiographical memories being central to everyday mental life, there is no agreed model of autobiographical memory retrieval, and we lack an understanding of the neural mechanisms involved. This precludes principled interventions to manage or alleviate memory deficits, and to test the efficacy of treatment regimens. This knowledge gap exists because autobiographical memories are challenging to study – they are immersive, multi-faceted, multi-modal, can stretch over long timescales and are grounded in the real world. One missing piece of the puzzle concerns the millisecond neural dynamics of autobiographical memory retrieval. Surprisingly, there are very few magnetoencephalography (MEG) studies examining such recall, despite the important insights this could offer into the activity and interactions of key brain regions such as the hippocampus and ventromedial prefrontal cortex. In this talk I will describe a series of MEG studies aimed at uncovering the neural circuitry underpinning the recollection of autobiographical memories, and how this changes as memories age. I will end by describing our progress on leveraging an exciting new technology – optically pumped MEG (OP-MEG) which, when combined with virtual reality, offers the opportunity to examine millisecond neural responses from the whole brain, including deep structures, while participants move within a virtual environment, with the attendant head motion and vestibular inputs.

Multitask performance humans and deep neural networks

Humans and other primates exhibit rich and versatile behaviour, switching nimbly between tasks as the environmental context requires. I will discuss the neural coding patterns that make this possible in humans and deep networks. First, using deep network simulations, I will characterise two distinct solutions to task acquisition (“lazy” and “rich” learning) which trade off learning speed for robustness, and depend on the initial weights scale and network sparsity. I will chart the predictions of these two schemes for a context-dependent decision-making task, showing that the rich solution is to project task representations onto orthogonal planes on a low-dimensional embedding space. Using behavioural testing and functional neuroimaging in humans, we observe BOLD signals in human prefrontal cortex whose dimensionality and neural geometry are consistent with the rich learning regime. Next, I will discuss the problem of continual learning, showing that behaviourally, humans (unlike vanilla neural networks) learn more effectively when conditions are blocked than interleaved. I will show how this counterintuitive pattern of behaviour can be recreated in neural networks by assuming that information is normalised and temporally clustered (via Hebbian learning) alongside supervised training. Together, this work offers a picture of how humans learn to partition knowledge in the service of structured behaviour, and offers a roadmap for building neural networks that adopt similar principles in the service of multitask learning. This is work with Andrew Saxe, Timo Flesch, David Nagy, and others.

A brain-computer interface in prefrontal cortex that suppresses neural variability

COSYNE 2022

Counterfactual outcomes affect reward expectation and prediction errors in macaque frontal cortex

COSYNE 2022

Defining the role of a locus coeruleus-orbitofrontal cortex circuit in behavioral flexibility

COSYNE 2022

Distinct aversive states in the mouse medial prefrontal cortex.

COSYNE 2022

Frontal cortex neural correlations are reduced in the transformation to movement

COSYNE 2022

Frontal cortex neural correlations are reduced in the transformation to movement

COSYNE 2022

Internally Organized Abstract Task Maps in the Mouse Medial Frontal Cortex

COSYNE 2022

Internally Organized Abstract Task Maps in the Mouse Medial Frontal Cortex

COSYNE 2022

Irrational choice via curvilinear value geometry in ventromedial prefrontal cortex

COSYNE 2022

Irrational choice via curvilinear value geometry in ventromedial prefrontal cortex

COSYNE 2022

Neural sequence representation of stimulus value, response and surprise in hippocampus and prefrontal cortex

COSYNE 2022

Neural sequence representation of stimulus value, response and surprise in hippocampus and prefrontal cortex

COSYNE 2022

Orbitofrontal cortex is required to infer hidden task states during value-based decision making

COSYNE 2022

Orbitofrontal cortex is required to infer hidden task states during value-based decision making

COSYNE 2022

Pupil size anticipates exploration and predicts disorganization in prefrontal cortex

COSYNE 2022

Pupil size anticipates exploration and predicts disorganization in prefrontal cortex

COSYNE 2022

The rodent medial prefrontal cortex is composed of functionally distinct subregions

COSYNE 2022

The rodent medial prefrontal cortex is composed of functionally distinct subregions

COSYNE 2022

Abstract deliberation by visuomotor neurons in prefrontal cortex

COSYNE 2023

Coordinated geometric representations of learned knowledge in hippocampus and frontal cortex

COSYNE 2023

The desire to know: representations of information value in mouse orbitofrontal cortex during information seeking

COSYNE 2023

Dorsolateral prefrontal cortex is a key cortical locus for perceptual decisions

COSYNE 2023

Modeling the orbitofrontal cortex function in navigation through an RL-RNN implementation

COSYNE 2023

Orbitofrontal cortex forms representations of latent states during learning

COSYNE 2023

Population encoding and decoding of frontal cortex during natural communication in marmosets

COSYNE 2023

Signatures of belief representations in recurrent neural networks and prefrontal cortex

COSYNE 2023

Timing-dependent modulation of working memory by dopaminergic release in the prefrontal cortex

COSYNE 2023

Uncertainty-robust goal embedding in the prefrontal cortex for flexibly stable learning

COSYNE 2023

Context-dependent neural coding of utility in the frontal cortex of rats

COSYNE 2025

Flexible decision-making engages generalizable spiraling dynamical motifs in prefrontal cortex

COSYNE 2025

Neural correlates of memory-based flexible decision-making in prefrontal cortex

COSYNE 2025

Neural substrates of a symbolic action grammar in primate frontal cortex

COSYNE 2025

Prefrontal cortex represents spontaneous behavior as a succession of tasks

COSYNE 2025

Prefrontal cortex subregions provide distinct visual and behavioral feedback modulation to the primary Visual cortex

COSYNE 2025

An accessory prefrontal cortex–thalamus circuit sculpts maternal behavior in virgin female mice

FENS Forum 2024

Action-outcome based flexible behavior requires medial prefrontal cortex lead and its enhanced functional connectivity with dorsomedial striatum

FENS Forum 2024

Activation of parvalbumin+ interneurons in orbitofrontal cortex leads to higher functional connectivity, increased cerebral blood volume, and social dysregulation

FENS Forum 2024

Activity of distinct excitatory populations in prefrontal cortex during decision making in mice

FENS Forum 2024

Adrenergic receptors control of rebound depolarization in medial prefrontal cortex pyramidal neurons

FENS Forum 2024

Analysis of burst sequences in mouse prefrontal cortex during learning

Bernstein Conference 2024