James C. Houk

A sensitive low artifact TMB procedure for the demonstration of WGA-HRP in the CNS

A TMB reaction with increased sensitivity and lower artifact can be obtained by dividing the Mesulam reaction into two stages. Use of the modified reaction with HRP conjugated wheat germ agglutinin (WGA-HRP) yields a powerful technique for anterograde and retrograde tracing.

Models of the cerebellum and motor learning

This article reviews models of the cerebellum and motor learning starting with the landmark papers by Marr and Albus and going through present times. The unique architecture of the cerebellar cortex is ideally suited for pattern recognition, but how is pattern recognition incorporated into motor control and learning systems? The present analysis begins with a discussion of what the cerebellar cortex needs to regulate through its anatomically defined projections to premotor networks. Next we examine various models of how the microcircuitry in the cerebellar cortex may be used to achieve its regulatory functions. Having thus defined what it is that Purkinje cells in the cerebellar cortex must learn, we then evaluate theories of motor learning. We examine current models of synaptic plasticity, credit assignment and the generation of training information, indicating how they could function cooperatively to guide the processes of motor learning. Lesion studies carried out in the 19th century demonstrated that the cerebellum is important for coordinating movements (Florens, 1824). However, mechanistic models of the cerebellum awaited an analysis of the histology of the cerebellum (Braitenberg & Atwood, 1958), and combined analyses of histology and electrophysiology (Marr, 1969; Albus, 1971). The clear orthogonal relationships between parallel and climbing fibers and the dendritic trees of Purkinje cells convinced Braitenberg that the cerebellum functions as a timing organ. He viewed the parallel fibers as delay lines and climbing fibers as clock read-out mechanisms, with Purkinje cells firing only when there was a coincidence of a parallel fiber volley and a climbing fiber activation. In one of his examples, a Purkinje cell innervating an antagonist muscle fired at an appropriate time delay to terminate a movement at its intended target. Even though parallel fibers have small diameters and low conduction velocities, the time delays only amount to a few milliseconds, rather short for most problems in motor control. Another limitation of this theory is its requirement for foci of synchronized activation in the granular layer. For these and other reasons, Braitenberg’ s timing theory has not been as vigorously pursued as the learned pattern recognition theories developed subsequently by Marr (1969) and Albus (1971).

The role of the basal ganglia and cerebellum in language processing

The roles of the cerebellum and basal ganglia have typically been confined in the literature to motor planning and control. However, mounting evidence suggests that these structures are involved in more cognitive domains such as language processing. In the current study, we looked at effective connectivity (the influence that one brain region has on another) of the cerebellum and basal ganglia with regions thought to be involved in phonological processing, i.e. left inferior frontal gyrus and left lateral temporal cortex. We analyzed functional magnetic resonance imaging data (fMRI) obtained during a rhyming judgment task in adults using dynamic causal modeling (DCM). The results showed that the cerebellum has reciprocal connections with both left inferior frontal gyrus and left lateral temporal cortex, whereas the putamen has unidirectional connections into these two brain regions. Furthermore, the connections between cerebellum and these phonological processing areas were stronger than the connections between putamen and these areas. This pattern of results suggests that the putamen and cerebellum may have distinct roles in language processing. Based on research in the motor planning and control literature, we argue that the putamen engages in cortical initiation while the cerebellum amplifies and refines this signal to facilitate correct decision making.

Distributed motor commands in the limb premotor network

Neuroanatomical studies have demonstrated extensive interconnections between the motor cortex, red nucleus and cerebellum, forming a premotor network for controlling limb movement. Single-unit studies indicate that command signals for limb movements are distributed broadly throughout this network. Cellular studies have demonstrated multiple recurrent loops in this network, and the presence of excitatory and inhibitory amino acid neurotransmitters. A recent model suggests that movement commands are initiated by sensory inputs to these loops, and that positive feedback, regulated by inhibition from cerebellar Purkinje cells, distributes commands throughout the limb premotor network. This model offers a new framework for exploring relationships between basic neural mechanisms and concepts of motor performance that derive from experimental psychology.

Action selection and refinement in subcortical loops through basal ganglia and cerebellum

Subcortical loops through the basal ganglia and the cerebellum form computationally powerful distributed processing modules (DPMs). This paper relates the computational features of a DPMs loop through the basal ganglia to experimental results for two kinds of natural action selection. First, functional imaging during a serial order recall task was used to study human brain activity during the selection of sequential actions from working memory. Second, microelectrode recordings from monkeys trained in a step-tracking task were used to study the natural selection of corrective submovements. Our DPM-based model assisted in the interpretation of puzzling data from both of these experiments. We come to posit that the many loops through the basal ganglia each regulate the embodiment of pattern formation in a given area of cerebral cortex. This operation serves to instantiate different kinds of action (or thought) mediated by different areas of cerebral cortex. We then use our findings to formulate a model of the aetiology of schizophrenia.

Agents of the mind

The higher order circuitry of the brain is comprised of a large-scale network of cerebral cortical areas that are individually regulated by loops through subcortical structures, particularly through the basal ganglia and cerebellum. These subcortical loops have powerful computational architectures. Using, as an example, the relatively well-understood processing that occurs in the cortical/basal ganglionic/cerebellar distributed processing module that generates voluntary motor commands, I postulate that a network of analogous agents is an appropriate framework for exploring the dynamics of the mind.

Functional and anatomic differentiation between parvicellular and magnocellular regions of red nucleus in the monkey

Single unit recording in awake monkeys was used to search for functional differences between the two divisions of the red nucleus, and anatomical tracing of WGA-HRP was used to investigate inputs to the two divisions. We studied a total of 323 units in 4 red nuclei of two monkeys. Recording sites were identified in histological sections by the locations of lesions and the reconstruction of electrode tracks. Of the units in the RNm 98.5% discharged in high frequency bursts during movement. Only 52% showed reliable responses to somatosensory stimulation, and the responses observed were weaker than the movement-related discharge. None of the units recorded in the RNp showed strong movement-related discharge, and 51% were completely unresponsive during both motor and sensory tests. A dorsolateral group of medium-sized cells that overlaps the rostral half of the main RNm and the caudal pole of RNp appears to represent an extension of the magnocellular region. Retrograde transport of WGA-HRP indicated that some of these cells are rubrospinal neurons. Furthermore, the discharge properties of dorsolateral neurons are like the main RNm neurons, except for lower discharge rates and smaller spike amplitudes. Mouth movements are strongly represented in the dorsolateral region. Anterograde transport of WGA-HRP from the motor cortex demonstrated dense terminal label in RNp as contrasted with light label in RNm. Retrograde transport of WGA-HRP from RNm labeled many more cells in the cerebellar interpositus nucleus than in motor cortex. We concluded that input to RNm from the cerebellum is the likely source of the strong movement-related activity recorded from cells in the RNm. The absence of appreciable movement-related activity in parvicellular red nucleus provides a clear functional distinction between this division and the magnocellular division of the red nucleus.

Distributed representation of limb motor programs in arrays of adjustable pattern generators

This paper describes the current state of our exploration of how motor program concepts may be related to neural mechanisms. We have proposed a model of sensorimotor networks with architectures inspired by the anatomy and physiology of the cerebellum and its interconnections with the red nucleus and the motor cortex. We proposed the concept of rubrocerebellar and corticocerebellar information processing modules that function as adjustable pattern generators (APGs) capable of the storage, recall, and execution of motor programs. The APG array model described in this paper extends the single APG model of Houk et al. (1990) to an array of APGs whose collective activity controls movement of a simple two degree-of-freedom simulated limb. Our objective was to examine the APG array theory in a simple computational framework with a plausible relationship to anatomy and physiology. Results of simulation experiments show that the APG array model is capable of learning how to control movement of the simulated limb by adjusting distributed motor programs. Although the model is based on many simplifying assumptions, and the simulated motor control task is much simpler than an actual reaching task, these results suggest that the APG array model may provide a useful step toward a more comprehensive understanding of how neural mechanisms may generate motor programs.

Correlation of primate red nucleus discharge with muscle activity during free-form arm movements.

1. We recorded from 239 neurons located in the magnocellular division of the red nucleus of four alert macaque monkeys. At the same time, we recorded electromyographic (EMG) signals from as many as twenty electrodes chronically implanted on muscles of the shoulder, arm, forearm and hand. We recorded EMG signals for periods ranging from several months to a year. 2. The monkeys were trained to perform three free‐form food retrieval tasks, each of which activated all of the recorded muscles and most of the neurons. The ‘prehension’ task required simply that the monkey grasp a piece of food from a fixed point in space. The ‘barrier’ task required the monkey to reach around a small barrier to obtain the food, and the ‘Kluver’ task required that food be removed from small holes. During the prehension task, we found approximately equal numbers of neurons that were strongly active while the hand was being moved toward the target (70% of units), and while the food was being grasped (60%). Relatively few units were active as the hand was returned to the mouth (15%). 3. Data files of 1‐2 min duration were collected while the monkey performed a single behavioural task. Whenever possible, we recorded files for all three tasks from each neuron. For each file we calculated long time‐span analog cross‐correlations (+/‐ 1.28 s) between instantaneous neuronal firing rate and each of the full‐wave rectified, low‐pass filtered EMG signals. We used the peak correlation and the time of the peak as two summary measures of the functional relation between modulation of neuronal activity and EMG. 4. The magnitude of the strongest correlations was between 0.4 and 0.5 (normalized to a perfect correlation of +/‐ 1.0). Distal muscles were the most frequently correlated, and extensors were more frequently correlated than flexors. For all monkeys, the lags for well correlated muscles were distributed broadly about a uni‐modal value near 0 ms. Eighty five per cent of the correlations larger than or equal to 0.25 had peaks between ‐150 and 200 ms. 5. The activity of each neuron was represented in a muscle co‐ordinate system by an n‐dimensional ‘functional linkage vector’, each element of which was the peak correlation with one of n muscles. The vector for any given neuron points in a particular direction in muscle space, depending on the similarity between the activity of the neuron and the activity of each muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

A cerebellar model of timing and prediction in the control of reaching

A simplified model of the cerebellum was developed to explore its potential for adaptive, predictive control based on delayed feedback information. An abstract representation of a single Purkinje cell with multistable properties was interfaced, using a formalized premotor network, with a simulated single degree-of-freedom limb. The limb actuator was a nonlinear spring-mass system based on the nonlinear velocity dependence of the stretch reflex. By including realistic mossy fiber signals, as well as realistic conduction delays in afferent and efferent pathways, the model allowed the investigation of timing and predictive processes relevant to cerebellar involvement in the control of movement. The model regulates movement by learning to react in an anticipatory fashion to sensory feedback. Learning depends on training information generated from corrective movements and uses a temporally asymmetric form of plasticity for the parallel fiber synapses on Purkinje cells.