Research Overview
Neuronal mechanisms underlying the generation, maintenance, monitoring, and transformation of mental representations in working memory
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Our brain has the extraordinary ability to actively maintain and manipulate mental representations of sensory or abstract/conceptual nature. This ability is known as working memory. The mental image of a person we just met, or an address we are driving to, or today’s to-do list, or the sentence we are constructing to say next—they can all be maintained in working memory, even without the use of our senses. Representations in working memory can be manipulated by transforming them (e.g., mentally performing a mathematical calculation) or monitoring them (e.g., mentally going over a to-do list), among others. Our ability to manipulate representations—not to simply maintain or store them—is what makes working memory fundamental for other cognitive abilities such as attention, problem-solving, decision-making and action-planning, and is the core of human intelligence, imagination, and creativity.
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​One of the central research aims of the Mendoza-Halliday Lab is to understand the mechanisms underlying the manipulation (transformation and monitoring) of working memory representations at the level of single neurons, microcircuits, and neuronal populations across multiple brain regions. We also aim to understand the relationship between the mechanisms of working memory maintenance and manipulation, as well as how working memory mechanisms interact with and support other brain functions such as perception, attention, decision-making, and action-planning, among others.
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​To examine these mechanisms, we simultaneously monitor the activity of large numbers of individual neurons across cortical layers and across multiple brain regions using high-density laminar electrophysiological methods during the performance of complex visual cognitive tasks requiring the maintenance and manipulation (transformation or monitoring) of mental representations in working memory. This allows us to investigate how electrophysiological activity in different neurons, neuron types, cortical layers, and brain regions, as well as their communication, relates to these cognitive functions. To examine the causal role that neurons in different brain regions play in working memory maintenance and manipulation, we experimentally inactivate or activate these neurons using customized large-scale optogenetic methods we developed.
Optogenetic control of neuronal activity
(Schwerpunkt sculpture by Ralph Helmick)
Artistic photo by Diego Mendoza-Halliday
Methods for large-scale optogenetic inactivation of superficial cortex
Layer-specific oscillatory mechanisms of the cerebral cortex​
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One feature of the cortex that has been ignored by most electrophysiological studies is its anatomical organization into a six-layer motif, partly because it has been challenging to find a corresponding laminar motif of neural activity that is preserved across the cortex. In a large collaborative effort, we previously reported the discovery of a laminar motif of local field potential (LFP) activity that is preserved across a large number of cortical areas [LINK]. This motif is composed by an increasing deep-to-superficial layer gradient of gamma frequency LFP power peaking in layers 2/3, and an increasing superficial-to-deep gradient of alpha-beta power peaking in layers 5/6. This discovery demonstrated a preserved functional dissociation between superficial and deep layers across the cortex and suggest a ubiquitous layer and frequency-based mechanism for cortical computation. The discovery also opens up an entire new line of research.
Our lab is developing computational models of laminar LFP signals that can recreate the spectrolaminar motif, and that can also fit and parametrize real laminar LFP recordings. With these models, we are constructing a spectrolaminar framework to analyze and understand cortical oscillatory signals. With this framework, we aim to address fundamental question such as:
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Is the spectrolaminar motif present in the cortex of all mammals on Earth? Is there phylogenetic divergence in the spectrolaminar motif across species.
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​What are the neuron-level and circuit-level mechanisms that generate the oscillatory activity composing the spectrolaminar motif?
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What role do cortical oscillations composing the spectrolaminar motif play in cognitive functions?
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Our ultimate aim is to develop a generalized theory of cortical architecture and function that explains how precise variations in the canonical spectrolaminar and cytoarchitectonic motifs in each area enable it to specialize in a unique function, and how inter-areal variations of this motif lead to the diversity of functions performed across the cortex. This will require not only examining the cortical areas and functions studied directly in our lab, but also collaborating with other labs studying various cortical regions and functions.
Multi-area laminar
electrophysiological recordings
Spectrolaminar motif of LFP power
