Publications by authors named "Aaron Gruber"

Article Synopsis
  • - Deep Reinforcement Learning (DRL) is used to simulate how biological agents learn based on rewards, and researchers modified DRL to mimic the effects of dendritic spine loss seen in major depressive disorder (MDD).
  • - This simulated spine loss led to various MDD-like behaviors in the AI, such as loss of pleasure (anhedonia), increased impatience for rewards (temporal discounting), and changes in how the AI explores or exploits options.
  • - The findings suggest that MDD may be more related to reduced brain connectivity rather than just chemical imbalances, indicating potential treatment avenues that focus on enhancing brain plasticity and synapse formation.
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Psychedelic drugs have profound effects on perception, cognition and mood. How psychedelics affect neural signaling to produce these effects remains poorly understood. We investigated the effect of the classic psychedelic psilocybin on neural activity patterns and spatial encoding in the retrosplenial cortex of head-fixed mice navigating on a treadmill.

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The subgenual anterior cingulate cortex (sgACC) has been identified as a key brain area involved in various cognitive and emotional processes. While the sgACC has been implicated in both emotional valuation and emotional conflict monitoring, it is still unclear how this area integrates multiple functions. We characterized both single neuron and local field oscillatory activity in 14 patients undergoing sgACC deep brain stimulation for treatment-resistant depression.

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Neuronal activity gives rise to behavior, and behavior influences neuronal dynamics, in a closed-loop control system. Is it possible then, to find a relationship between the statistical properties of behavior and neuronal dynamics? Measurements of neuronal activity and behavior have suggested a direct relationship between scale-free neuronal and behavioral dynamics. Yet, these studies captured only local dynamics in brain sub-networks.

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Background: The ability of psychedelic compounds to profoundly alter mental function has been long known, but the underlying changes in cellular-level information encoding remain poorly understood.

Methods: We used two-photon microscopy to record from the retrosplenial cortex in head-fixed mice running on a treadmill before and after injection of the nonclassic psychedelic ibogaine (40 mg/kg intraperitoneally).

Results: We found that the cognitive map, formed by the representation of position encoded by ensembles of individual neurons in the retrosplenial cortex, was destabilized by ibogaine when mice had to infer position between tactile landmarks.

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Does the brain optimize itself for storage and transmission of information, and if so, how? The critical brain hypothesis is based in statistical physics and posits that the brain self-tunes its dynamics to a critical point or regime to maximize the repertoire of neuronal responses. Yet, the robustness of this regime, especially with respect to changes in the functional connectivity, remains an unsolved fundamental challenge. Here, we show that both scale-free neuronal dynamics and self-similar features of behavioral dynamics persist following significant changes in functional connectivity.

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Gastrointestinal tract (gut) inflammation increases stress and threat-coping behaviors, which are associated with altered activity in fear-related neural circuits, such as the basolateral amygdala and hippocampus. It remains to be determined whether inflammation from the gut affects neural activity by altering dendritic spines. We hypothesized that acute inflammation alters dendritic spines in a brain region-specific manner.

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When the outcome of a choice is less favorable than expected, humans and animals typically shift to an alternate choice option on subsequent trials. Several lines of evidence indicate that this "lose-shift" responding is an innate sensorimotor response strategy that is normally suppressed by executive function. Therefore, the lose-shift response provides a covert gauge of cognitive control over choice mechanisms.

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Psychostimulants such as d-amphetamine (AMPH) often have behavioral effects that appear paradoxical within the framework of optimal choice theory. AMPH typically increases task engagement and the effort animals exert for reward, despite decreasing reward valuation. We investigated neural correlates of this phenomenon in the anterior cingulate cortex (ACC), a brain structure implicated in signaling cost-benefit utility.

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Inflammatory bowel disease (IBD) is characterized by relapsing periods of gut inflammation, and is comorbid with depression, anxiety, and cognitive deficits. Animal models of IBD that explore the behavioral consequences almost exclusively use acute models of gut inflammation, which fails to recapitulate the cyclic, chronic nature of IBD. This study sought to identify behavioral differences in digging, memory, and stress-coping strategies in mice exposed to one (acute) or three (chronic) cycles of gut inflammation, using the dextran sodium sulfate (DSS) model of colitis.

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Closed-loop neurophysiological systems use patterns of neuronal activity to trigger stimuli, which in turn affect brain activity. Such closed-loop systems are already found in clinical applications, and are important tools for basic brain research. A particularly interesting recent development is the integration of closed-loop approaches with optogenetics, such that specific patterns of neuronal activity can trigger optical stimulation of selected neuronal groups.

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Behavior provides important insights into neuronal processes. For example, analysis of reaching movements can give a reliable indication of the degree of impairment in neurological disorders such as stroke, Parkinson disease, or Huntington disease. The analysis of such movement abnormalities is notoriously difficult and requires a trained evaluator.

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Decision-making in the mammalian brain typically involves multiple brain structures within the midbrain, thalamus, striatum, limbic system, and cortex. Although task specific contributions of each brain region have been identified, neurons responding to reinforcement have been found throughout these structures. We sought to determine if any brain area, or cluster of areas, are the source of information, and if the fidelity of information varies among the areas.

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Oscillatory activity is a ubiquitous property of brain signals, and yet relatively few studies have investigated how the phase of such ongoing oscillations affects our cognition. One of the main findings in this field is that the phase of electroencephalography (EEG) in the alpha band can affect perception of milliseconds-long stimuli. However, the importance of the phase of EEG for processing more naturalistic stimuli, which have a much longer duration, is still not clear.

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Multiple neural systems contribute to choice adaptation following reinforcement. Recent evidence suggests that the lateral habenula (LHb) plays a key role in such adaptations, particularly when reinforcements are worse than expected. Here, we investigated the effects of bilateral LHb lesions on responding in a binary choice task with no discriminatory cues.

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Animals tend to repeat actions that are associated with reward delivery, whereas they tend to shift responses to alternate choices following reward omission. These so-called win-stay and lose-shift responses are employed by a wide range of animals in a variety of decision-making scenarios, and depend on dissociated regions of the striatum. Specifically, lose-shift responding is impaired by extensive excitotoxic lesions of the lateral striatum.

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The anterior cingulate cortex (ACC) encodes information supporting mnemonic and cognitive processes. We show here that a rat's position can be decoded with high spatiotemporal resolution from ACC activity. ACC neurons encoded the current state of the animal and task, except for brief excursions that sometimes occurred at target feeders.

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The propensity of animals to shift choices immediately after unexpectedly poor reinforcement outcomes is a pervasive strategy across species and tasks. We report here on the memory supporting such lose-shift responding in humans, assessed using a binary choice task in which random responding is the optimal strategy. Participants exhibited little lose-shift responding when fully attending to the task, but this increased by 30%-40% in participants that performed with additional cognitive load that is known to tax executive systems.

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Although male and female rats appear to perform differently in some tasks, a clear picture of sex differences in decision-making has yet to develop. This is in part due to significant variability arising from differences in strains and tasks. The aim of this study was to characterize the effects of sex on specific response elements in a reinforcement learning task so as to help identify potential explanations for this variability.

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Animals quickly learn to approach sources of food. Here, we report on a form of approach in which rats made volitional orofacial contact with inactive feeders between trials of a self-paced operant task. This extraneous feeder sampling (EFS) was never reinforced and therefore imposed an opportunity and effort cost.

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Δ-9-Tetrahydrocannabinol (THC) is the main psychoactive component of marijuana and has potent effects on decision-making, including a proposed reduction in cognitive flexibility. We demonstrate here that acute THC administration differentially affects some of the processes that contribute to cognitive flexibility. Specifically, THC reduces lose-shift responding in which female rats tend to immediately shift choice responses away from options that result in reward omission on the previous trial.

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Gambling studies have described a "near-miss effect" wherein the experience of almost winning increases gambling persistence. The near-miss has been proposed to inflate the value of preceding actions through its perceptual similarity to wins. We demonstrate here, however, that it acts as a conditioned stimulus to positively or negatively influence valuation, dependent on reward expectation and cognitive engagement.

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The reinforcement learning (RL) paradigm allows agents to solve tasks through trial-and-error learning. To be capable of efficient, long-term learning, RL agents should be able to apply knowledge gained in the past to new tasks they may encounter in the future. The ability to predict actions' consequences may facilitate such knowledge transfer.

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The mammalian brain is thought to use a version of Model-based Reinforcement Learning (MBRL) to guide "goal-directed" behavior, wherein animals consider goals and make plans to acquire desired outcomes. However, conventional MBRL algorithms do not fully explain animals' ability to rapidly adapt to environmental changes, or learn multiple complex tasks. They also require extensive computation, suggesting that goal-directed behavior is cognitively expensive.

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