The evolutionary origins of volition

It appears to be a straightforward implication of distributed cognition principles that there is no integrated executive control system (e.g. Brooks 1991, Clark 1997). If distributed cognition is taken as a credible paradigm for cognitive science this in turn presents a challenge to volition because the concept of volition assumes integrated information processing and action control. For instance the process of forming a goal should integrate information about the available action options. If the goal is acted upon these processes should control motor behavior. If there were no executive system then it would seem that processes of action selection and performance couldn’t be functionally integrated in the right way. The apparently centralized decision and action control processes of volition would be an illusion arising from the competitive and cooperative interaction of many relatively simple cognitive systems. Here I will make a case that this conclusion is not well-founded. Prima facie it is not clear that distributed organization can achieve coherent functional activity when there are many complex interacting systems, there is high potential for interference between systems, and there is a need for focus. Resolving conflict and providing focus are key reasons why executive systems have been proposed (Baddeley 1986, Norman and Shallice 1986, Posner and Raichle 1994). This chapter develops an extended theoretical argument based on this idea, according to which selective pressures operating in the evolution of cognition favor high order control organization with a ‘highest-order’ control system that performs executive functions

Inferring and perturbing cell fate regulomes in human brain organoids

Self-organizing neural organoids grown from pluripotent stem cells(1-3) combined with single-cell genomic technologies provide opportunities to examine gene regulatory networks underlying human brain development. Here we acquire single-cell transcriptome and accessible chromatin data over a dense time course in human organoids covering neuroepithelial formation, patterning, brain regionalization and neurogenesis, and identify temporally dynamic and brain-region-specific regulatory regions. We developed Pando-a flexible framework that incorporates multi-omic data and predictions of transcription-factor-binding sites to infer a global gene regulatory network describing organoid development. We use pooled genetic perturbation with single-cell transcriptome readout to assess transcription factor requirement for cell fate and state regulation in organoids. We find that certain factors regulate the abundance of cell fates, whereas other factors affect neuronal cell states after differentiation. We show that the transcription factor GLI3 is required for cortical fate establishment in humans, recapitulating previous research performed in mammalian model systems. We measure transcriptome and chromatin accessibility in normal or GLI3-perturbed cells and identify two distinct GLI3 regulomes that are central to telencephalic fate decisions: one regulating dorsoventral patterning with HES4/5 as direct GLI3 targets, and one controlling ganglionic eminence diversification later in development. Together, we provide a framework for how human model systems and single-cell technologies can be leveraged to reconstruct human developmental biology

Vector Field Embryogeny

We present a novel approach toward evolving artificial embryogenies, which omits the graph representation of gene regulatory networks and directly shapes the dynamics of a system, i.e., its phase space. We show the feasibility of the approach by evolving cellular differentiation, a basic feature of both biological and artificial development. We demonstrate how a spatial hierarchy formulation can be integrated into the framework and investigate the evolution of a hierarchical system. Finally, we show how the framework allows the investigation of allometry, a biological phenomenon, and its role for evolution. We find that direct evolution of allometric change, i.e., the evolutionary adaptation of the speed of system states on transient trajectories in phase space, is advantageous for a cellular differentiation task

What does the amygdala contribute to social cognition?

The amygdala has received intense recent attention from neuroscientists investigating its function at the molecular, cellular, systems, cognitive, and clinical level. It clearly contributes to processing emotionally and socially relevant information, yet a unifying description and computational account have been lacking. The difficulty of tying together the various studies stems in part from the sheer diversity of approaches and species studied, in part from the amygdala's inherent heterogeneity in terms of its component nuclei, and in part because different investigators have simply been interested in different topics. Yet, a synthesis now seems close at hand in combining new results from social neuroscience with data from neuroeconomics and reward learning. The amygdala processes a psychological stimulus dimension related to saliency or relevance; mechanisms have been identified to link it to processing unpredictability; and insights from reward learning have situated it within a network of structures that include the prefrontal cortex and the ventral striatum in processing the current value of stimuli. These aspects help to clarify the amygdala's contributions to recognizing emotion from faces, to social behavior toward conspecifics, and to reward learning and instrumental behavior

Genetic correlates of the development of theta event related oscillations in adolescents and young adults

The developmental trajectories of theta band (4–7 Hz) event-related oscillations (EROs), a key neurophysiological constituent of the P3 response, were assessed in 2170 adolescents and young adults ages 12 to 25. The theta EROs occurring in the P3 response, important indicators of neurocognitive function, were elicited during the evaluation of task-relevant target stimuli in visual and auditory oddball tasks. Associations between the theta EROs and genotypic variants of 4 KCNJ6 single nucleotide polymorphisms (SNPs) were found to vary with age, sex, scalp location, and task modality. Three of the four KCNJ6 SNPs studied here were found to be significantly associated with the same theta EROs in adults in a previous family genome wide association study. Since measures of the P3 response have been found to be a useful endophenotypes for the study of a number of clinical and behavioral disorders, studies of genetic effects on its development in adolescents and young adults may illuminate neurophysiological factors contributing to the onset of these conditions

Behavioral And Heart-Defined Attention in Infants at High Genetic Risk for Autism

Characterizing early predictors of autism facilitates earlier identification, diagnosis and treatment. Although aberrant visual attention is one of the earliest identified predictors of autism and may play an integral role in developmental cascades that contribute to associated impairments, the emergence of atypical attention in infancy is poorly understood. The present dissertation includes three related manuscripts examining early patterns of visual attention in two infant samples at elevated risk for autism: infant siblings of children with autism (ASIBs) and infants with fragile X syndrome (FXS). Together, these manuscripts identify patterns of abnormal heart defined attention among ASIBs (Study 1), investigate the association between abnormal heart defined attention and attention orienting in ASIBs (Study 2), and examine the generalizability of these patterns to infants with FXS (Study 3). Together, findings provide novel evidence of atypical heart-defined and associated behavioral attention in ASIBs and FXS, with abnormalities emerging as early as 6 months of age in ASIBs. Importantly, Study 3 revealed diverging patterns of attention-arousal relationships in infants with FXS, suggesting potentially unique biological pathways subserving similar patterns of abnormal behavior across two infant samples at high risk for autism. These findings provide evidence of both shared and diverging endophenotypic features of autism in infants at high genetic risk, potentially informing early detection and interventions that target mechanisms, rather than symptoms, of impairment

Information processing in biology

To survive, organisms must respond appropriately to a variety of challenges posed by a dynamic and uncertain environment. The mechanisms underlying such responses can in general be framed as input-output devices which map environment states (inputs) to associated responses (output. In this light, it is appealing to attempt to model these systems using information theory, a well developed mathematical framework to describe input-output systems. Under the information theoretical perspective, an organism’s behavior is fully characterized by the repertoire of its outputs under different environmental conditions. Due to natural selection, it is reasonable to assume this input-output mapping has been fine tuned in such a way as to maximize the organism’s fitness. If that is the case, it should be possible to abstract away the mechanistic implementation details and obtain the general principles that lead to fitness under a certain environment. These can then be used inferentially to both generate hypotheses about the underlying implementation as well as predict novel responses under external perturbations. In this work I use information theory to address the question of how biological systems generate complex outputs using relatively simple mechanisms in a robust manner. In particular, I will examine how communication and distributed processing can lead to emergent phenomena which allow collective systems to respond in a much richer way than a single organism could

The free energy principle induces neuromorphic development

We show how any finite physical system with morphological, i.e. three-dimensional embedding or shape, degrees of freedom and locally limited free energy will, under the constraints of the free energy principle, evolve over time towards a neuromorphic morphology that supports hierarchical computations in which each ‘level’ of the hierarchy enacts a coarse-graining of its inputs, and dually, a fine-graining of its outputs. Such hierarchies occur throughout biology, from the architectures of intracellular signal transduction pathways to the large-scale organization of perception and action cycles in the mammalian brain. The close formal connections between cone-cocone diagrams (CCCD) as models of quantum reference frames on the one hand, and between CCCDs and topological quantum field theories on the other, allow the representation of such computations in the fully-general quantum-computational framework of topological quantum neural networks

The molecular basis of the development and diversity of proprioceptive neurons : a story of surviving and thriving

Proprioception, also known as the sixth sense, describes the sensation of our body position and movement. Its proper function is essential for our daily activities from coarse movements, e.g. locomotion, to precise movements, e.g. playing instruments. The key executors of proprioception are proprioceptive neurons (PNs), the peripheral sensory neurons which continuously monitor the status of muscles, and provide feedback to the central circuits to regulate motor outputs. This thesis aims to extend our current understanding of the development (study I) and functional organization (study II) of PNs. To contextualize the two studies, this thesis first reviews the relevant literatures in the chapter of Introduction, followed by the presentation of the major findings. In study I, we revisit the long-standing neurotrophic hypothesis, which features the exclusive role of target-derived factors in controlling programmed cell death in developing nervous system. Using PNs as a model, we try to understand whether neurons themselves are actively engaged or passively selected during this competition to survive. We find that right before the cell death period, PNs exhibit diverse molecular profiles, which underlie their different responsiveness to target-derived factors and maturation states. The PNs with certain molecular signatures out compete others in this selection to survive, showing that the intrinsic properties of neurons endow some neurons with competitive advantages and are involved in the regulation of neuronal death together with environmental factors. In study II, we use single-cell RNA sequencing to analyze the molecular profiles of adult PNs in mice. Through immunological, genetic and viral labeling, we identify three groups of PNs that correspond to the known functional subtypes (Ia, Ib and II) and provide long-awaited genetic markers to target them individually. We also unveil subtypes within Ia- and II-PNs (Ia1/2/3-PNs and II1/2/3/4-PNs) that have stereotyped distribution along the spinal cord, selective muscle targets, and unique molecular attributes, indicating an unanticipated and sophisticated organization of proprioceptive feedback. While all other subtypes are established neonatally before the onset of coordinated movements, Ia-PN subtypes emerge later along with the maturation of the animal’s motor skills, suggesting the influence of sensory experience on the diversification of Ia-PN subtypes. This is supported by the experiment in which Ia-PN subtypes adjust their relative abundance (Ia1-PNs switch to Ia2/3-PNs) after sustained exercise training, showing the plasticity of the proprioceptive system to adapt to changing motor activity