Systems Neuroscience

Project Summary Understanding how neural circuits create animal behavior requires knowing the system-wide activity patterns that connect sensory experience to motor activities, all within the full set of feedback loops by which actuated motor decisions modulate the animal's perceptions of itself and the outside world during naturally executed and unrestrained behaviors. Mechanistic understanding further requires interpretation of system-wide activity patterns in terms of the connectivity, synaptic, and cellular properties of all relevant neurons.

Project Summary/Abstract Impairments in social functioning is a prominent, debilitating symptom in many neuropsychiatric disorders, such as autism spectrum disorders, schizophrenia, and major depressive disorder. Currently the neural underpinnings of these social deficits are poorly understood, and effective therapeutic approaches are still lacking. Elucidation of the neural circuit mechanisms for social behaviors will improve our understanding of the disease mechanisms of neuropsychiatric disorders, facilitating the development of potent treatments.

Project Abstract Our project aims to form a multi-site consortium that will carry out fundamental exper- iments to elucidate the mesoscopic and microscopic neural dynamics underlying human memory and use direct brain stimulation as a manipulative tool to study those dynamics. Additionally, we seek to create a dynamical timeseries model that predicts the evolution of brain activity during cognitive tasks and incorporates the e ects of stimulation-induced perturbations on the system.

PROJECT SUMMARY The thalamic reticular nucleus (TRN), the major source of thalamic inhibition, plays essential roles in sensory processing, arousal and cognition. Receiving inputs from cortical and subcortical regions, this structure is strategically positioned to influence thalamo-cortical interactions. During quiescence, the TRN participate in sleep rhythm generation, sleep stability and memory consolidation, while in active states, TRN neurons contribute to sensory filtering underlying attention.

NEURONAL CIRCUITS FOR CONTEXT-DRIVEN BIAS IN AUDITORY CATEGORIZATION In everyday life, because both sensory signals and neuronal responses are noisy, important cognitive tasks, such as auditory categorization, are based on uncertain information. To overcome this limitation, listeners incorporate other types of signals, such as the statistics of sounds over short and long time scales and signals from other sensory modalities into their categorization decision processes. At the behavioral level, such contextual signals bias categorization by shifting the listener's psychometric curve.

Project Summary/Abstract Speech perception is inherently multisensory: when conversing with someone that we can see, our brains combine auditory information from the voice with visual information from the face. Speech perception lies at the heart of our interactions with other people and is thus one of our most important cognitive abilities. However, there is a large gap in our knowledge about this uniquely human skill because most experimental techniques available in humans suffer from poor spatiotemporal resolution.

PROJECT SUMMARY The basic mechanisms underlying comprehension of spoken language are unknown. We are only beginning to understand how the human brain extracts the most fundamental linguistic elements (consonants and vowels) from a complex and highly variable acoustic signal. Traditional theories have posited a ‘universal’ phonetic inventory shared by all humans, but this has been challenged by other newer theories that each language has its own unique and specialized code.

PROJECT SUMMARY Actions are not mediated solely by cortical processes but rely on communication within basal ganglia- thalamocortical loops. Speech is one example, although how the basal ganglia participate in this uniquely human behavior is not clear, due to a lack of empirical data. For instance, the leading computational model of speech production ignores the hyperdirect cortical pathway to the subthalamic nucleus (STN), a basal ganglia node that has been implicated in multiple cognitive processes relevant to speech production (e.g.

Project Summary/Abstract Decades of research and clinical observations have established that successful spatial navigation and memory depend on the hippocampus and associated structures in the medial temporal lobe (MTL), including entorhinal, perirhinal and parahippocampal cortices [1, 2]. It is thought that the supporting neuronal mechanisms rely on key oscillatory patterns of activity within the MTL that change dynamically when navigating through an environment [3-10].

Project Summary The rapid formation of new memories and the recall of old memories to inform decisions is essential for human cognition, but the underlying neural mechanisms remain poorly understood. The long-term goal of this research is a circuit-level understanding of human memory to enable the development of new treatments for the devastating effects of memory disorders. Our experiments utilize the rare opportunity to record in-vivo from human single neurons simultaneously in multiple brain areas in patients undergoing treatment for drug resistant epilepsy.