A Neural Model of Timed Response Learning in the Cerebellum

A spectral timing model is developed to explain how the cerebellum learns adaptively timed responses during the rabbit's conditioned nictitating membrane response (NMR). The model posits two learning sites that respectively enable conditioned excitation and timed disinhibition of the response. Long-term potentiation of mossy fiber pathways projecting to interpositus nucleus cells allows conditioned excitation of the response's adaptive gain. Long-term depression of parallel fiber- Purkinje cell synapses in the cerebellar cortex allows learning of an adaptively timed reduction in Purkinje cell inhibition of the same nuclear cells. A spectrum of partially timed responses summate to generate an accurately timed population response. In agreement with physiological data, the model Purkinje cell activity decreases in the interval following the onset of the conditioned stimulus, and nuclear cell responses match conditioned response (CR) topography. The model reproduces key behavioral features of the NMR, including the properties that CR peak amplitude occurs at the unconditioned stimulus (US) onset, a discrete CR peak shift occurs with a change in interstimulus interval (ISI) between conditioned stim- ulus (CS) and US, mixed training at two different ISis produces a double-peaked CR, CR acquisition and rate of responding depend unimodally on the lSI, CR onset latency decreases during training, and maladaptively-timed, small-amplitude CRs result from ablation of cerebellar cortex.National Science Foundation (IRI-90-24877); Office of Naval Research (N00014-92-J-1309); Air Force Office of Scientific Research (F49620-92-J-0225

Metabotropic Glutamate Receptor Activation in Cerebelar Purkinje Cells as Substrate for Adaptive Timing of the Classicaly Conditioned Eye Blink Response

To understand how the cerebellum adaptively times the classically conditioned nictitating membrane response (NMR), a model of the metabotropic glutamate receptor (mGluR) second messenger system in cerebellar Purkinje cells is constructed. In the model slow responses, generated postsynaptically by mGluR-mediated phosphoinositide hydrolysis, and calcium release from intracellular stores, bridge the interstimulus interval (ISI) between the onset of parallel fiber activity associated with the conditioned stimulus (CS) and climbing fiber activity associated with unconditioned stimulus (US) onset. Temporal correlation of metabotropic responses and climbing fiber signals produces persistent phosphorylation of both AMPA receptors and Ca2+-dependent K+ channels. This is responsible for long-term depression (LTD) of AMPA receptors. The phosphorylation of Ca2+-dependent K+ channels leads to a reduction in baseline membrane potential and a reduction of Purkinje cell population firing during the CS-US interval. The Purkinje cell firing decrease disinhibits cerebellar nuclear cells which then produce an excitatory response corresponding to the learned movement. Purkinje cell learning times the response, while nuclear cell learning can calibrate it. The model reproduces key features of the conditioned rabbit NMR: Purkinje cell population response is properly timed, delay conditioning occurs for ISIs of up to four seconds while trace conditioning occurs only at shorter ISIs, mixed training at two different ISis produces a double-peaked response, and ISIs of 200-400ms produce maximal responding. Biochemical similarities between timed cerebellar learning and photoreceptor transduction, and circuit similarities between the timed cerebellar circuit and a timed dentate-CA3 hippocampal circuit, are noted.Office of Naval Research (N00014- 92-J-4015, N00014-92-J-1309, N00014-95-1-0409); Air Force Office of Scientific Research (F49620-92-J-0225);National Science Foundation (IRI-90-24877

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

Adaptive Neural Models of Queuing and Timing in Fluent Action

Temporal structure in skilled, fluent action exists at several nested levels. At the largest scale considered here, short sequences of actions that are planned collectively in prefrontal cortex appear to be queued for performance by a cyclic competitive process that operates in concert with a parallel analog representation that implicitly specifies the relative priority of elements of the sequence. At an intermediate scale, single acts, like reaching to grasp, depend on coordinated scaling of the rates at which many muscles shorten or lengthen in parallel. To ensure success of acts such as catching an approaching ball, such parallel rate scaling, which appears to be one function of the basal ganglia, must be coupled to perceptual variables, such as time-to-contact. At a fine scale, within each act, desired rate scaling can be realized only if precisely timed muscle activations first accelerate and then decelerate the limbs, to ensure that muscle length changes do not under- or over-shoot the amounts needed for the precise acts. Each context of action may require a much different timed muscle activation pattern than similar contexts. Because context differences that require different treatment cannot be known in advance, a formidable adaptive engine-the cerebellum-is needed to amplify differences within, and continuosly search, a vast parallel signal flow, in order to discover contextual "leading indicators" of when to generate distinctive parallel patterns of analog signals. From some parts of the cerebellum, such signals controls muscles. But a recent model shows how the lateral cerebellum, such signals control muscles. But a recent model shows how the lateral cerebellum may serve the competitive queuing system (in frontal cortex) as a repository of quickly accessed long-term sequence memories. Thus different parts of the cerebellum may use the same adaptive engine system design to serve the lowest and the highest of the three levels of temporal structure treated. If so, no one-to-one mapping exists between levels of temporal structure and major parts of the brain. Finally, recent data cast doubt on network-delay models of cerebellar adaptive timing.National Institute of Mental Health (R01 DC02852

Isoperimetric Partitioning: A New Algorithm for Graph Partitioning

Temporal structure is skilled, fluent action exists at several nested levels. At the largest scale considered here, short sequences of actions that are planned collectively in prefronatal cortex appear to be queued for performance by a cyclic competitive process that operates in concert with a parallel analog representation that implicitly specifies the relative priority of elements of the sequence. At an intermediate scale, single acts, like reaching to grasp, depend on coordinated scaling of the rates at which many muscles shorten or lengthen in parallel. To ensure success of acts such as catching an approaching ball, such parallel rate scaling, which appears to be one function of the basal ganglia, must be coupled to perceptual variables such as time-to-contact. At a finer scale, within each act, desired rate scaling can be realized only if precisely timed muscle activations first accelerate and then decelerate the limbs, to ensure that muscle length changes do not under- or over- shoot the amounts needed for precise acts. Each context of action may require a different timed muscle activation pattern than similar contexts. Because context differences that require different treatment cannot be known in advance, a formidable adaptive engine-the cerebellum-is needed to amplify differences within, and continuosly search, a vast parallel signal flow, in order to discover contextual "leading indicators" of when to generate distinctive patterns of analog signals. From some parts of the cerebellum, such signals control muscles. But a recent model shows how the lateral cerebellum may serve the competitive queuing system (frontal cortex) as a repository of quickly accessed long-term sequence memories. Thus different parts of the cerebellum may use the same adaptive engine design to serve the lowest and highest of the three levels of temporal structure treated. If so, no one-to-one mapping exists between leveels of temporal structure and major parts of the brain. Finally, recent data cast doubt on network-delay models of cerebellar adaptive timing.National Institute of Mental Health (R01 DC02582

A Scalable Model of Cerebellar Adaptive Timing and Sequencing: The Recurrent Slide and Latch (RSL) Model

From the dawn of modern neural network theory, the mammalian cerebellum has been a favored object of mathematical modeling studies. Early studies focused on the fan-out, convergence, thresholding, and learned weighting of perceptual-motor signals within the cerebellar cortex. This led in the proposals of Albus (1971; 1975) and Marr (1969) to the still viable idea that the granule cell stage in the cerebellar cortex performs a sparse expansive recoding of the time-varying input vector. This recoding reveals and emphasizes combinations (of input state variables) in a distributed representation that serves as a basis for the learned, state-dependent control actions engendered by cerebellar outputs to movement related centers. Although well-grounded as such, this perspective seriously underestimates the intelligence of the cerebellar cortex. Context and state information arises asynchronously due to the heterogeneity of sources that contribute signals to compose the cerebellar input vector. These sources include radically different sensory systems - vision, kinesthesia, touch, balance and audition - as well as many stages of the motor output channel. To make optimal use of available signals, the cerebellum must be able to sift the evolving state representation for the most reliable predictors of the need for control actions, and to use those predictors even if they appear only transiently and well in advance of the optimal time for initiating the control action. Such a cerebellar adaptive timing competence has recently been experimentally verified (Perrett, Ruiz, & Mauk, 1993). This paper proposes a modification to prior, population, models for cerebellar adaptive timing and sequencing. Since it replaces a population with a single clement, the proposed Recurrent Slide and Latch (RSL) model is in one sense maximally efficient, and therefore optimal from the perspective of scalability.Defense Advanced Research Projects Agency and the Office of Naval Research (N00014-92-J-1309, N00014-93-1-1364, N00014-95-1-0409)

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

A neural network model of adaptively timed reinforcement learning and hippocampal dynamics

A neural model is described of how adaptively timed reinforcement learning occurs. The adaptive timing circuit is suggested to exist in the hippocampus, and to involve convergence of dentate granule cells on CA3 pyramidal cells, and NMDA receptors. This circuit forms part of a model neural system for the coordinated control of recognition learning, reinforcement learning, and motor learning, whose properties clarify how an animal can learn to acquire a delayed reward. Behavioral and neural data are summarized in support of each processing stage of the system. The relevant anatomical sites are in thalamus, neocortex, hippocampus, hypothalamus, amygdala, and cerebellum. Cerebellar influences on motor learning are distinguished from hippocampal influences on adaptive timing of reinforcement learning. The model simulates how damage to the hippocampal formation disrupts adaptive timing, eliminates attentional blocking, and causes symptoms of medial temporal amnesia. It suggests how normal acquisition of subcortical emotional conditioning can occur after cortical ablation, even though extinction of emotional conditioning is retarded by cortical ablation. The model simulates how increasing the duration of an unconditioned stimulus increases the amplitude of emotional conditioning, but does not change adaptive timing; and how an increase in the intensity of a conditioned stimulus "speeds up the clock", but an increase in the intensity of an unconditioned stimulus does not. Computer simulations of the model fit parametric conditioning data, including a Weber law property and an inverted U property. Both primary and secondary adaptively timed conditioning are simulated, as are data concerning conditioning using multiple interstimulus intervals (ISIs), gradually or abruptly changing ISis, partial reinforcement, and multiple stimuli that lead to time-averaging of responses. Neurobiologically testable predictions are made to facilitate further tests of the model.Air Force Office of Scientific Research (90-0175, 90-0128); Defense Advanced Research Projects Agency (90-0083); National Science Foundation (IRI-87-16960); Office of Naval Research (N00014-91-J-4100

Attentive Learning of Sequential Handwriting Movements: A Neural Network Model

Defense Advanced research Projects Agency and the Office of Naval Research (N00014-95-1-0409, N00014-92-J-1309); National Science Foundation (IRI-97-20333); National Institutes of Health (I-R29-DC02952-01)