Frontmatter

Cornell University Press eBooks · 2022-08-26

Decoding and perturbing decision states in real time

Nature · 2021 · 138 citations

• Computer Science
• Artificial Intelligence
• Computer Science

Differential Encoding in Prefrontal Cortex Projection Neuron Classes Across Cognitive Tasks

SSRN Electronic Journal · 2020-01-01 · 2 citations

Remote, brain region–specific control of choice behavior with ultrasonic waves

Science Advances · 2020 · 129 citations

• Computer Science
• Neuroscience
• Computer Science

The ability to modulate neural activity in specific brain circuits remotely and systematically could revolutionize studies of brain function and treatments of brain disorders. Sound waves of high frequencies (ultrasound) have shown promise in this respect, combining the ability to modulate neuronal activity with sharp spatial focus. Here, we show that the approach can have potent effects on choice behavior. Brief, low-intensity ultrasound pulses delivered noninvasively into specific brain regions of macaque monkeys influenced their decisions regarding which target to choose. The effects were substantial, leading to around a 2:1 bias in choices compared to the default balanced proportion. The effect presence and polarity was controlled by the specific target region. These results represent a critical step towards the ability to influence choice behavior noninvasively, enabling systematic investigations and treatments of brain circuits underlying disorders of choice.

Opportunities and limitations of genetically modified nonhuman primate models for neuroscience research

Proceedings of the National Academy of Sciences · 2020 · 122 citations

• Neuroscience
• Psychology
• Cognitive science

The recently developed new genome-editing technologies, such as the CRISPR/Cas system, have opened the door for generating genetically modified nonhuman primate (NHP) models for basic neuroscience and brain disorders research. The complex circuit formation and experience-dependent refinement of the human brain are very difficult to model in vitro, and thus require use of in vivo whole-animal models. For many neurodevelopmental and psychiatric disorders, abnormal circuit formation and refinement might be at the center of their pathophysiology. Importantly, many of the critical circuits and regional cell populations implicated in higher human cognitive function and in many psychiatric disorders are not present in lower mammalian brains, while these analogous areas are replicated in NHP brains. Indeed, neuropsychiatric disorders represent a tremendous health and economic burden globally. The emerging field of genetically modified NHP models has the potential to transform our study of higher brain function and dramatically facilitate the development of effective treatment for human brain disorders. In this paper, we discuss the importance of developing such models, the infrastructure and training needed to maximize the impact of such models, and ethical standards required for using these models.

Value and choice as separable, stable representations in orbitofrontal cortex

bioRxiv (Cold Spring Harbor Laboratory) · 2020-01-02 · 1 citations

Abstract Value-based decision-making operates on multiple variables—including offer value, choice, expected outcome, and recent history—each functioning at different times in the decision process. Orbitofrontal cortex (OFC) has long been implicated in value-based decision-making, but it is unclear how downstream circuits might read out complex OFC responses into separate representations of the relevant variables to support different cognitive functions at specific times. We recorded from single neurons in OFC while macaque monkeys made cost-benefit decisions to juice offers. Using a novel analysis—optimal targeted dimensionality reduction—we discovered orthogonal, static dimensions (i.e. linear combinations of neurons) that selectively represented the value, choice, and expected reward of the present and, separately, previous offers. The neural composition of most representations was stable over discrete time periods that aligned to concurrent cognitive demands. We applied a new set of statistical methods to determine that the sensitivity, specificity and stability of the representations were greater than expected from the low-level features—dimensionality and temporal smoothness—of the responses alone. The separability and stability of OFC representations suggest a mechanism by which downstream circuits can read out specific task-relevant variables at appropriate times.

Differential encoding in prefrontal cortex projection neuron classes across cognitive tasks

bioRxiv (Cold Spring Harbor Laboratory) · 2020-03-14 · 13 citations

SUMMARY Single-cell transcriptomics has been widely applied to classify neurons in the mammalian brain, while systems neuroscience has historically analyzed the encoding properties of cortical neurons without considering cell types. Here we examine how specific transcriptomic types of mouse prefrontal cortex (PFC) projection neurons relate to axonal projections and encoding properties across multiple cognitive tasks. We found that most types projected to multiple targets, and most targets received projections from multiple types, except PFC→PAG (periaqueductal gray). By comparing Ca 2+ -activity of the molecularly homogeneous PFC→PAG type against two heterogeneous classes in several two-alternative choice tasks in freely-moving mice, we found that all task-related signals assayed were qualitatively present in all examined classes. However, PAG-projecting neurons most potently encoded choice in cued tasks, whereas contralateral PFC-projecting neurons most potently encoded reward context in an uncued task. Thus, task signals are organized redundantly, but with clear quantitative biases across cells of specific molecular-anatomical characteristics.

Value and choice as separable and stable representations in orbitofrontal cortex

Nature Communications · 2020-07-10 · 43 citations

Value-based decision-making requires different variables-including offer value, choice, expected outcome, and recent history-at different times in the decision process. Orbitofrontal cortex (OFC) is implicated in value-based decision-making, but it is unclear how downstream circuits read out complex OFC responses into separate representations of the relevant variables to support distinct functions at specific times. We recorded from single OFC neurons while macaque monkeys made cost-benefit decisions. Using a novel analysis, we find separable neural dimensions that selectively represent the value, choice, and expected reward of the present and previous offers. The representations are generally stable during periods of behavioral relevance, then transition abruptly at key task events and between trials. Applying new statistical methods, we show that the sensitivity, specificity and stability of the representations are greater than expected from the population's low-level features-dimensionality and temporal smoothness-alone. The separability and stability suggest a mechanism-linear summation over static synaptic weights-by which downstream circuits can select for specific variables at specific times.

Differential encoding in prefrontal cortex projection neuron classes across cognitive tasks

Cell · 2020-12-17 · 128 citations