Hidden Markov Model

When navigating a familiar environment, your behavior may vary depending on your goals. For example, you might take a detour to check out a restaurant you have been curious about, but if you're in a rush, you will opt for the shortest route. Our research focuses on how the brain's neural population, particularly in regions associated with goal-directed behavior (the orbitofrontal cortex, OFC) and navigation (the retrosplenial cortex, RSC), orchestrates the transition between competing goals during navigation. To explore this, we designed a virtual-reality maze task for two Rhesus monkeys, wher

Animals employ different behavioral strategies to achieve the goal of sensory navigation. However, the factors that drive switches between different strategies---and the neural mechanisms underlying them---remain largely unknown. The nematode worm C. elegans is known to exhibit distinct “steering” and “turning” strategies during navigation, where steering involves continuous, gradual changes in orientation, and turning involves infrequent, major reorientation events. It is commonly assumed that the worm’s responses to sensory input, whether steering or turning, are independent behavioral actio

Cognitive maps confer animals with flexible intelligence by representing spatial, temporal, and abstract relationships that can be used to shape thought, planning, and behavior. Cognitive maps have been observed in the hippocampus, but their algorithmic form and the processes by which they are learned remain obscure. We employed large-scale, longitudinal two-photon calcium imaging to record activity from thousands of neurons in the CA1 region of the hippocampus while mice learned to efficiently collect rewards from two subtly different linear tracks in virtual reality. The results provide a de

Sex-steroid hormones powerfully influence internal states, mood, and social drives. In many species, including mice, females exhibit increased sexual receptivity during the peri-ovulatory phase following an estrogen surge. However, we lack understanding of how these hormones alter neural computations to regulate social behaviors, particularly their effects on neural dynamics in key regions for top-down control of social choice, such as the medial prefrontal cortex (mPFC). One potential, but unexplored role of the estrogen surge is to enable persistent neural states to facilitate costly behavio

Social interactions across animal species are governed by the interplay between multimodal sensory information and the internal states of each animal. Here, we investigate this interplay in female Drosophila (fruit fly) as she engages with the male during courtship, a highly dynamic social behavior. Previous work has shown that the male fly's courtship song is shaped by the subtle feedback cues from the female and is influenced by his internal states1,2. However, in the case of females, prior work has focused only on predicting her walking speed averaged over minutes3,4; her fast timescale res

…survival, and mice serve as valuable models in neuroscience for studying these processes. In this study, we introduce a novel maze framework to investigate learning and adaptability in mice, specifically focusing on humanized App knock-in models of Alzheimer's disease. The maze mimics decision-making scenarios, similar to when foraging, with an optimal reward path leading to a target with sucrose pellets. Decision nodes introduce off-reward routes to dead-ends or loops, creating a challenge requiring mice to balance exploration w

Social pain, the emotional pain caused by aversive experiences with one’s social group, can have deleterious effects on both mental and physical health1–3. Multiple theories have proposed that the experience of social pain can modulate physical pain5,6, but a neural mechanism has never been discovered. To address this gap, we have designed a novel paradigm, termed the FOMO (Fear of Missing Out) Task, to systematically investigate the effects of Social Exclusion. During Social Exclusion (SE), mice have all been trained to associate a cue with reward delivery, and the subject is then separated f

…a trio of domain-specific generative models (Fig 1a) within prefrontal (PFC) nodes of the Default-Mode Network (DMN), and integrate within its parietal nodes, forming the basis for our dynamic consciousness.Smoothed binary ratings of prediction updates for State changes, Agent beliefs, and Action sequences from an online sample were used as parametric regressors for the GLMs. These ratings indicating experience shifts

In an ever-changing environment, flexible control of behaviour is crucial for survival. Across species, adaptive processes like attention and motivation manifest as flexibly fluctuating, brain-wide states. Although these states likely share commonalities across species, classical tasks are highly species-specific, preventing direct cross-species comparisons.Here we examine naturalistic fluctuations of attention across three species—mice, monkeys, and humans—completing the same highly immersive virtual reality (VR) foraging task (Fig.1A). This allows us to continuously track behavioural decisio

Cognitive maps confer animals with flexible intelligence by representing spatial, temporal, and abstract relationships that can be used to shape thought, planning, and behavior. Cognitive maps have been observed in the hippocampus, but their algorithmic form and the processes by which they are learned remain obscure. Here, we employed large-scale, longitudinal two-photon calcium imaging to record activity from thousands of neurons in the CA1 region of the hippocampus while mice learned to efficiently collect rewards from two subtly different versions of linear tracks in virtual reality. The r

When experts are immersed in a task, a natural assumption is that their brains prioritize task-related activity. Accordingly, most efforts to understand neural activity during well-learned tasks focus on cognitive computations and task-related movements. Surprisingly, we observed that during decision-making, the cortex-wide activity of multiple cell types is dominated by movements, especially “uninstructed movements”, that are spontaneously expressed. These observations argue that animals execute expert decisions while performing richly varied, uninstructed movements that profoundly shape neu

…Applying a hidden Markov model (HMM) to cortical LFPs, we consistently identified three stable states in each mouse: a high-frequency state (dominated by gam

…and optogenetics to measure and then model learned odor-navigation strategies in worms. Specifically, we modelled navigation using a Mixture of

High-density electrophysiological probes have substantially increased the spatial resolution and scale of neural recordings. Popular spike sorting algorithms, e.g. Kilosort (Pachitariu et al. 2016), SpyKING CIRCUS, etc., use waveform template matching to isolate single units from the large-scale recordings, but these algorithms make numerous errors which often require hours of manual curation to correct. Bursting neurons pose an additional challenge in spike-sorting: the shape and amplitude of a neuron’s waveform can change significantly over the course of a burst. Thus, waveform shape- based

Essential features of the world are often hidden and must be inferred by constructing internal models based on indirect evidence. During naturalistic foraging, animals must continually choose between trying to exploit a depleting food source at their current location and leaving to explore a new source at the expense of costly travel epochs. When is it best to leave the current site for another one? In a deterministic environment, the optimal strategy is to leave the current site when the immediate rate of reward drops below the average rate - a stimulus-bound strategy, assigning each action a

Working memory (WM) is central for cognition and is impaired in many brain disorders including those hypothetically mediated by NMDA receptor (NMDAR) hypofunction. Evidence suggests that network attractor states underlie WM maintenance and that failures are mostly caused by fluctuation-driven transitions, but direct evidence for this is still lacking. To investigate what makes WM fail we used a simple two-alternative delayed response task in which mice listen to a lateralized auditory stimulus and, after a variable delay (duration D=0-10 s), they have to lick the associated lateral port. Mice

…Our method models trial-to-trial state switches with a hidden Markov model (HMM)

Recent work has shown that rodent decision-making relies on distinct latent or hidden states that switch on a timescale of tens to hundreds of trials [Ashwood 2021; Bolkan, Stone 2021; Weilnhammer 2021]. However, the neural basis for these states, and the contributions of different brain regions to state-dependent decision-making strategies, remains an important open problem. Here we address this challenge by performing a model-based analysis of decision-making data acquired during multi-region laser-scanning inactivation of dorsal cortex. We analyzed optogenetic inactivation data from mice pe