The Physiology and Computation of Pyramidal Neurons

A variety of neural signals have been measured as correlates to consciousness. In particular, late current sinks in layer 1, distributed activity across the cortex, and feedback processing have all been implicated. What are the physiological underpinnings of these signals? What computational role do they play in the brain? Why do they correlate to consciousness? This thesis begins to answer these questions by focusing on the pyramidal neuron. As the primary communicator of long-range feedforward and feedback signals in the cortex, the pyramidal neuron is set up to play an important role in establishing distributed representations. Additionally, the dendritic extent, reaching layer 1, is well situated to receive feedback inputs and contribute to current sinks in the upper layers. An investigation of pyramidal neuron physiology is therefore necessary to understand how the brain creates, and potentially uses, the neural correlates of consciousness. An important part of this thesis will be in establishing the computational role that dendritic physiology plays. In order to do this, a combined experimental and modeling approach is used.

This thesis beings with single-cell experiments in layer 5 and layer 2/3 pyramidal neurons. In both cases, dendritic nonlinearities are characterized and found to be integral regulators of neural output. Particular attention is paid to calcium spikes and NMDA spikes, which both exist in the apical dendrites, considerable distances from the spike initiation zone. These experiments are then used to create detailed multicompartmental models. These models are used to test hypothesis regarding spatial distribution of membrane channels, to quantify the effects of certain experimental manipulations, and to establish the computational properties of the single cell. We find that the pyramidal neuron physiology can carry out a coincidence detection mechanism. Further abstraction of these models reveals potential mechanisms for spike time control, frequency modulation, and tuning. Finally, a set of experiments are carried out to establish the effect of long-range feedback inputs onto the pyramidal neuron. A final discussion then explores a potential way in which the physiology of pyramidal neurons can establish distributed representations, and contribute to consciousness.

Quantifying synergistic information

Within the microcosm of information theory, I explore what it means for a system to be functionally irreducible. This is operationalized as quantifying the extent to which cooperative or “synergistic” effects enable random variables X₁, ... , X_n to predict (have mutual information about) a single target random variable Y . In Chapter 1, we introduce the problem with some emblematic examples. In Chapter 2, we show how six different measures from the existing literature fail to quantify this notion of synergistic mutual information. In Chapter 3 we take a step towards a measure of synergy which yields the first nontrivial lowerbound on synergistic mutual information. In Chapter 4, we find that synergy is but the weakest notion of a broader concept of irreducibility. In Chapter 5, we apply our results from Chapters 3 and 4 towards grounding Giulio Tononi’s ambitious φ measure which attempts to quantify the magnitude of consciousness experience.

Real-World Social Cognition: Context Effects in Face and Threat Processing

As borne out by everyday social experience, social cognition is highly dependent on context, modulated by a host of factors that arise from the social environment in which we live. While streamlined laboratory research provides excellent experimental control, it can be limited to telling us about the capabilities of the brain under artificial conditions, rather than elucidating the processes that come into play in the real world. Consideration of the impact of ecologically valid contextual cues on social cognition will improve the generalizability of social neuroscience findings also to pathology, e.g., to psychiatric illnesses. To help bridge between laboratory research and social cognition as we experience it in the real world, this thesis investigates three themes: (1) increasing the naturalness of stimuli with richer contextual cues, (2) the potentially special contextual case of social cognition when two people interact directly, and (3) a third theme of experimental believability, which runs in parallel to the first two themes. Focusing on the first two themes, in work with two patient populations, we explore neural contributions to two topics in social cognition. First, we document a basic approach bias in rare patients with bilateral lesions of the amygdala. This finding is then related to the contextual factor of ambiguity, and further investigated together with other contextual cues in a sample of healthy individuals tested over the internet, finally yielding a hierarchical decision tree for social threat evaluation. Second, we demonstrate that neural processing of eye gaze in brain structures related to face, gaze, and social processing is differently modulated by the direct presence of another live person. This question is investigated using fMRI in people with autism and controls. Across a range of topics, we demonstrate that two themes of ecological validity — integration of naturalistic contextual cues, and social interaction — influence social cognition, that particular brain structures mediate this processing, and that it will be crucial to study interaction in order to understand disorders of social interaction such as autism.