Acetylcholine neuromodulation in normal and abnormal learning and memory: vigilance control in waking, sleep, autism, amnesia, and Alzheimer's disease

This article provides a unified mechanistic neural explanation of how learning, recognition, and cognition break down during Alzheimer's disease, medial temporal amnesia, and autism. It also clarifies whey there are often sleep disturbances during these disorders. A key mechanism is how acetylcholine modules vigilance control in cortical layer

Interplay between pleiotropy and secondary selection determines rise and fall of mutators in stress response

Dramatic rise of mutators has been found to accompany adaptation of bacteria in response to many kinds of stress. Two views on the evolutionary origin of this phenomenon emerged: the pleiotropic hypothesis positing that it is a byproduct of environmental stress or other specific stress response mechanisms and the second order selection which states that mutators hitchhike to fixation with unrelated beneficial alleles. Conventional population genetics models could not fully resolve this controversy because they are based on certain assumptions about fitness landscape. Here we address this problem using a microscopic multiscale model, which couples physically realistic molecular descriptions of proteins and their interactions with population genetics of carrier organisms without assuming any a priori fitness landscape. We found that both pleiotropy and second order selection play a crucial role at different stages of adaptation: the supply of mutators is provided through destabilization of error correction complexes or fluctuations of production levels of prototypic mismatch repair proteins (pleiotropic effects), while rise and fixation of mutators occur when there is a sufficient supply of beneficial mutations in replication-controlling genes. This general mechanism assures a robust and reliable adaptation of organisms to unforeseen challenges. This study highlights physical principles underlying physical biological mechanisms of stress response and adaptation

Towards a Unified Theory of Neocortex: Laminar Cortical Circuits for Vision and Cognition

A key goal of computational neuroscience is to link brain mechanisms to behavioral functions. The present article describes recent progress towards explaining how laminar neocortical circuits give rise to biological intelligence. These circuits embody two new and revolutionary computational paradigms: Complementary Computing and Laminar Computing. Circuit properties include a novel synthesis of feedforward and feedback processing, of digital and analog processing, and of pre-attentive and attentive processing. This synthesis clarifies the appeal of Bayesian approaches but has a far greater predictive range that naturally extends to self-organizing processes. Examples from vision and cognition are summarized. A LAMINART architecture unifies properties of visual development, learning, perceptual grouping, attention, and 3D vision. A key modeling theme is that the mechanisms which enable development and learning to occur in a stable way imply properties of adult behavior. It is noted how higher-order attentional constraints can influence multiple cortical regions, and how spatial and object attention work together to learn view-invariant object categories. In particular, a form-fitting spatial attentional shroud can allow an emerging view-invariant object category to remain active while multiple view categories are associated with it during sequences of saccadic eye movements. Finally, the chapter summarizes recent work on the LIST PARSE model of cognitive information processing by the laminar circuits of prefrontal cortex. LIST PARSE models the short-term storage of event sequences in working memory, their unitization through learning into sequence, or list, chunks, and their read-out in planned sequential performance that is under volitional control. LIST PARSE provides a laminar embodiment of Item and Order working memories, also called Competitive Queuing models, that have been supported by both psychophysical and neurobiological data. These examples show how variations of a common laminar cortical design can embody properties of visual and cognitive intelligence that seem, at least on the surface, to be mechanistically unrelated.National Science Foundation (SBE-0354378); Office of Naval Research (N00014-01-1-0624

How does the Cerebral Cortex Work? Learning, Attention, and Grouping by the Laminar Circuits of Visual Cortex

The organization of neocortex into layers is one of its most salient anatomical features. These layers include circuits that form functional columns in cortical maps. A major unsolved problem concerns how bottom-up, top-down, and horizontal interactions are organized within cortical layers to generate adaptive behaviors. This article models how these interactions help visual co1tex to realize: (I) the binding process whereby cortex groups distributed data into coherent object representations; (2) the attentional process whereby cortex selectively processes important events; and (3) the developmental and learning processes whereby cortex shapes its circuits to match environmental constraints. New computational ideas about feedback systems suggest how neocortex develops and learns in a stable way, and why top-down attention requires converging bottom-up inputs to fully activate cortical cells, whereas perceptual groupings do not.Defense Advanced Research Projects Agency; National Science Foundation (IRI-97-20333); Office of Naval Research (N00014-95-1-0409, N00014-95-1-0657

Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems

A generic mechanism - networked buffering - is proposed for the generation of robust traits in complex systems. It requires two basic conditions to be satisfied: 1) agents are versatile enough to perform more than one single functional role within a system and 2) agents are degenerate, i.e. there exists partial overlap in the functional capabilities of agents. Given these prerequisites, degenerate systems can readily produce a distributed systemic response to local perturbations. Reciprocally, excess resources related to a single function can indirectly support multiple unrelated functions within a degenerate system. In models of genome:proteome mappings for which localized decision-making and modularity of genetic functions are assumed, we verify that such distributed compensatory effects cause enhanced robustness of system traits. The conditions needed for networked buffering to occur are neither demanding nor rare, supporting the conjecture that degeneracy may fundamentally underpin distributed robustness within several biotic and abiotic systems. For instance, networked buffering offers new insights into systems engineering and planning activities that occur under high uncertainty. It may also help explain recent developments in understanding the origins of resilience within complex ecosystems. \ud \u

The hippocampus and cerebellum in adaptively timed learning, recognition, and movement

The concepts of declarative memory and procedural memory have been used to distinguish two basic types of learning. A neural network model suggests how such memory processes work together as recognition learning, reinforcement learning, and sensory-motor learning take place during adaptive behaviors. To coordinate these processes, the hippocampal formation and cerebellum each contain circuits that learn to adaptively time their outputs. Within the model, hippocampal timing helps to maintain attention on motivationally salient goal objects during variable task-related delays, and cerebellar timing controls the release of conditioned responses. This property is part of the model's description of how cognitive-emotional interactions focus attention on motivationally valued cues, and how this process breaks down due to hippocampal ablation. The model suggests that the hippocampal mechanisms that help to rapidly draw attention to salient cues could prematurely release motor commands were not the release of these commands adaptively timed by the cerebellum. The model hippocampal system modulates cortical recognition learning without actually encoding the representational information that the cortex encodes. These properties avoid the difficulties faced by several models that propose a direct hippocampal role in recognition learning. Learning within the model hippocampal system controls adaptive timing and spatial orientation. Model properties hereby clarify how hippocampal ablations cause amnesic symptoms and difficulties with tasks which combine task delays, novelty detection, and attention towards goal objects amid distractions. When these model recognition, reinforcement, sensory-motor, and timing processes work together, they suggest how the brain can accomplish conditioning of multiple sensory events to delayed rewards, as during serial compound conditioning.Air Force Office of Scientific Research (F49620-92-J-0225, F49620-86-C-0037, 90-0128); Advanced Research Projects Agency (ONR N00014-92-J-4015); Office of Naval Research (N00014-91-J-4100, N00014-92-J-1309, N00014-92-J-1904); National Institute of Mental Health (MH-42900

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

Neural Dynamics of Autistic Behaviors: Cognitive, Emotional, and Timing Substrates

What brain mechanisms underlie autism and how do they give rise to autistic behavioral symptoms? This article describes a neural model, called the iSTART model, which proposes how cognitive, emotional, timing, and motor processes may interact together to create and perpetuate autistic symptoms. These model processes were originally developed to explain data concerning how the brain controls normal behaviors. The iSTART model shows how autistic behavioral symptoms may arise from prescribed breakdowns in these brain processes.Air Force Office of Scientific Research (F49620-01-1-0397); Office of Naval Research (N00014-01-1-0624

Linking Visual Development and Learning to Information Processing: Preattentive and Attentive Brain Dynamics

National Science Foundation (SBE-0354378); Office of Naval Research (N00014-95-1-0657

The Laminar Organization of Visual Cortex: A Unified View of Development, Learning, and Grouping

Why are all sensory and cognitive neocortex organized into layered circuits? How do these layers organize circuits that form functional columns in cortical maps? How do bottom-up, top-down, and horizontal interactions within the cortical layers generate adaptive behaviors. This chapter summarizes an evolving neural model which suggests how these interactions help the visual cortex to realize: (1) the binding process whereby cortex groups distributed data into coherent object representations; (2) the attentional process whereby cortex selectively processes important events; and (3) the developmental and learning processes whereby cortex shapes its circuits to match environmental constraints. It is suggested that the mechanisms which achieve property (3) imply properties of (I) and (2). New computational ideas about feedback systems suggest how neocortex develops and learns in a stable way, and why top-down attention requires converging bottom-up inputs to fully activate cortical cells, whereas perceptual groupings do not.Defense Advanced Research Projects Agency and the Office of Naval Research (N00014-95-1-0409); National Science Foundation (IRI-97-20333); Office of Naval Research (N00014-95-1-0657