Jeff Wickens

Space, time and dopamine.

In recent years, dopamine has emerged as a key neurotransmitter that is crucially involved in incentive motivation and reinforcement learning. Dopamine release is evoked by rewards. The extensive divergence of outputs from a small number of dopaminergic neurons suggests a spatially nonselective action of dopamine, but it reinforces the specific actions that led to reward. How is this achieved? We propose that the selectivity of dopamine effects is achieved by the timing of dopamine release in relation to the activity of glutamatergic synapses, rather than by spatial localization of the dopamine signal to specific synaptic contacts. The synaptic mechanisms of these actions are unknown but reduced levels of dopamine, for example in Parkinsons disease, leads to a paucity of behavioural output, whereas its excess production has been associated with psychiatric problems. Clearly, there are therapeutic imperatives that require a better understanding of how dopamine functions at a synaptic level.

Cortical cell assemblies: a possible mechanism for motor programs.

The concept of a motor program has been used to interpret a diverse range of empirical findings related to preparation and initiation of voluntary movement. In the absence of an underlying mechanism, its exploratory power has been limited to that of an analogy with running a stored computer program. We argue that the theory of cortical cell assemblies suggests a possible neural mechanism for motor programming. According to this view, a motor program may be conceptualized as a cell assembly, which is stored in the form of strengthened synaptic connections between cortical pyramidal neurons. These connections determine which combinations of corticospinal neurons are activated when the cell assembly is ignited. The dynamics of cell assembly ignition are considered in relation to the problem of serial order. These considerations lead to a plausible neural mechanism for the programming of movements and movement sequences that is compatible with the effects of precue information and sequence length on reaction times. Anatomical and physiological guidelines for future quantitative models of cortical cell assemblies are suggested. By taking into account the parallel re-entrant loops between the cerebral cortex and basal ganglia, the theory of cortical cell assemblies suggests a mechanism for motor plans that involve longer sequences. The suggested model is compared with other existing neural network models for motor programming.

Basal ganglia: structure and computations

Until recently the basal ganglia of the mammalian brain have attracted little attention from theoretical neurobiologists. Traditional views of the functioning of the basal ganglia are based on their biomedical importance in disorders such as Parkinsons disease. Their contribution to normal brain functions has remained poorly understood. Experimental investigations over the past few decades have produced a wealth of detailed information about the structure of the basal ganglia and the physiological properties of their component neurones. It has become evident that the basal ganglia play a role in the selection and performance of learnt behaviours, and also in the effects of reinforcement on acquisition and maintenance of new behaviours. At present it is difficult to link the symptoms of basal ganglia disorders to these basic facts, in part because very few theoretical models attempt to incorporate the information that is now available. Computational modelling can help to advance theoretical understanding ...

Interactions of glutamate and dopamine in a computational model of the striatum

A network model of simplified striatal principal neurons with mutual inhibition was used to investigate possible interactions between cortical glutamatergic and nigral dopaminergic afferents in the neostriatum. Glutamatergic and dopaminergic inputs were represented by an excitatory synaptic conductance and a slow membrane potassium conductance, respectively. Neuronal activity in the model was characterized by episodes of increased action potential firing rates of variable duration and frequency. Autocorrelation histograms constructed from the action potential activity of striatal model neurons showed that reducing peak excitatory conductance had the effect of increasing interspike intervals. On the other hand, the maximum value of the dopamine-sensitive potassium conductance was inversely related to the duration of firing episodes and the maximal firing rates. A smaller potassium conductance restored normal firing rates in the most active neurons at the expense of a larger proportion of neurons showing reduced activity. Thus, a homogeneous network with mutual inhibition can produce equally complex dynamics as have been proposed to occur in a striatal network with two neuron populations that are oppositely regulated by dopamine. Even without mutual inhibition it appears that increased dopamine concentrations could partially compensate for the effects of reduced glutamatergic input in individual neurons.

Abnormal Striatal BOLD Responses to Reward Anticipation and Reward Delivery in ADHD

Altered reward processing has been proposed to contribute to the symptoms of attention deficit hyperactivity disorder (ADHD). The neurobiological mechanism underlying this alteration remains unclear. We hypothesize that the transfer of dopamine release from reward to reward-predicting cues, as normally observed in animal studies, may be deficient in ADHD. Functional magnetic resonance imaging (fMRI) was used to investigate striatal responses to reward-predicting cues and reward delivery in a classical conditioning paradigm. Data from 14 high-functioning and stimulant-naïve young adults with elevated lifetime symptoms of ADHD (8 males, 6 females) and 15 well-matched controls (8 males, 7 females) were included in the analyses. During reward anticipation, increased blood-oxygen-level-dependent (BOLD) responses in the right ventral and left dorsal striatum were observed in controls, but not in the ADHD group. The opposite pattern was observed in response to reward delivery; the ADHD group demonstrated significantly greater BOLD responses in the ventral striatum bilaterally and the left dorsal striatum relative to controls. In the ADHD group, the number of current hyperactivity/impulsivity symptoms was inversely related to ventral striatal responses during reward anticipation and positively associated with responses to reward. The BOLD response patterns observed in the striatum are consistent with impaired predictive dopamine signaling in ADHD, which may explain altered reward-contingent behaviors and symptoms of ADHD.

Striatal mechanisms in Parkinson’s disease: new insights from computer modeling

We review data and hypotheses concerning the functional anatomy of the striatum and the role of its corticostriatal and nigrostriatal afferents in Parkinsons disease (PD). Starting from molecular mechanisms of glutamatergic and dopaminergic actions in the striatum we have developed a compartmental model of striatal principal neurons that displays a significant degree of biological realism. Simulations of a network of striatal projection neurons under conditions likely to be found in healthy subjects as well as untreated and therapeutic situations of advanced PD provide clues concerning the dynamics of neuronal interactions and their possible effects on downstream motor structures in the generation of positive and negative motor symptoms. We present tentative biological explanations of the symptoms of rigidity and akinesia in PD leading to predictions concerning the origin of abnormal movements and the beneficial effects of dopaminergic treatment. Although these attempts are not yet sufficient to account for the complexity of clinical symptoms found in PD they can guide further empirical research and foster fruitful interactions between experimentalists, theoreticians, and clinicians in unraveling the functional anatomy of the basal ganglia.

The Contribution of the Striatum to Cortical Function

In the struggle for survival the ability to learn to associate temporally contiguous events is clearly advantageous. By forming such associations it becomes possible to reconstruct the external world from the fragments of information impinging on the senses. Equally so, it is important to be able to learn from the effects of actions directed outward upon the external world. Only then does it becomes possible to learn how to act upon the world in order to obtain a desired result. Thus, there appear to be at least two different types of learning. The distinction between these two types of learning is logical as well as psychological. This has been pointed out in various terms by a number of authors (Hirsh 1974; Mishkin et al. 1984; Miller 1988).

Corticostriatal interactions in neuromotor programming

Abstract Considerable evidence suggests that the neostriatum contributes to certain aspects of motor programming. However, the neostriatum does not appear to be a site at which the motor programmes are stored. A likely site for the storage of motor programmes is the cerebral cortex, especially areas which receive input from the neostriatum via the globus pallidus and thalamus. A motor programme may be conceptualized as a cell assembly, which is stored in the form of strengthened synaptic connections between cortical pyramidal neurones. These connections constrain the combinations of movements and the sequence that will result when the cell assembly is activated. This model for a motor programme may be used to explain, in terms of the dynamical behaviour of cortical cell assemblies, how a specific goal can consistently be attained by patterns of muscular activity that are highly variable. The contribution of the corticostriatal interactions may be ensure that cortical activity is attracted towards a state which corresponds to the goal of the movement.

Abstracts of the Seventeenth International Aijstralasian Winter Conference on Brain Research Queenstown New Zealand August 1999

It has been recognised that in order to study the displacement, timing and co-ordination of articulatory components (i.e., tongue. lips, jaw) in speech production it is desirable to obtain high-resolution movement data on multiple structures inside and outside the vocal tract. Until recently, with the exception of X-ray techniques such as cineradiography, the study 0. speech movements has been hindered by the inaccessibility of the oral cavity during speech. X-ray techniques are generally not used because of unacceptable radiation exposure. The aim of the present study was to demonstrate the use of a new physiological device, the electromagnetic articulograph, for assessing articulatory dysfunction subsequent to traumatic brain injury. The components of the device together with the measuring principle are described and data collected from a single case presented. A 19 year-old male who exhibited dysarthria subsequent to a traumatic brain injury was fitted wit 2 the electromagnetic articulograph (Carstens AG-100) and a kinematic analysis of his tongue movements during production of the lingual consonants it, s, k/ within single syllable words was performed. Examination of kinematic parameters including movemmt trajectories, velocity, and acceleration revealed differences in the speed and accuracy of his tongue movements compared to those produced by a non-neurologically impaired adult male. It was concluded that the articulograph is a useful device for diagnosing speed and accuracy disorders in tongue movements during speech and that the device has potential for incorporation into physiologically based rehabilitation programs as a real-time biofeedback instrument.Dysfunction of the articulatory subsystem (i.c.. the lips, tongue, and jaw) has bccn identified as a major contributor to the reduction in speech intelligibility experienced by a high proportion of people with multiple sclerosis (MS). In particular. consonant imprecision has been reported to be the articulatory deficit that contributes most to variations in overall intelligibility of MS speakers. Electropalatography(EPG) IS an instrurncntal technique that visually documents the location and timing of tongue-topalatc contacts during speech. Although such a technique would be valuablc in objectively assessing the articulatory disturbances exhibited by individuals with dysarthria ia motor speech disorder) associated with MS, to-date no such study ha< been reported. The aim of the present study was to use EPG to assess tongue-to-palate contact patterns and articulatory timing in patients with dysarthria associated with MS. A dysarthric participant with a diagnosis of definite MS was fitted with an acrylic EPG palate (Reading EPG.?) and asked to read aloud a list of single syllable words which contained lingual consonants in the word-initial position and in consonant clusters. Each mord was repeated five times. The EPG palate was specifically moulded to tit the participants hard palate and contained 62 electrodes that detected the tongue contacts. A non-neurologically impaired participant matched for age and sex servcd as a control. The results of the study revealed that the tongue-to-palate contacts produced by the participant with MS varied from those produced by the control in a number of ways in regard to spatial configurations and timing characteristics exhibited. The rcsults arc discussed in relation to the neuropathophysiological effects of MS on speech production. The potcntial use of EPG in programs for treating speech disorders associated with MS will be highlightcd.No single standardised version (including standardised stimuli and administration instructions) of the Stroop Test (Stroop, 1935) exists. Instead, numerous versions of this task, with varying stimuli, administration guides and scoring procedures are used both clinically and in research settings. While several adaptations of Stroop-type have been created no one type has gained prominence either clinically or experimentally. When the Golden Stroop appeared commercially as a package measure (Golden, 1978) the administration guide suggested that items could be read either in columns or rows. Some research suggesting that reading down in columns rather than across rows reduced the degree to which reading skills influenced final scores was cited. An adaptation of the traditional Stroop test, the California Older Adult Stroop Test (COAST; Pachana, Marcopulos, Yoash-Gantz, and Thompson, 1995), has been developed specifically for use with a geriatric population, utilising larger typeface, fewer items (50) per trial, and more easily distinguished colours (red, yellow, and green). These two tests were compared in terms of administration instructions, rate of errors, and their acceptability to head-injured older adults. Administration was vulnerable to confounds of both speed and err,x rate when instructions varied in the Golden version. Furthermore, blue- green colour-,,onfusion was a significant problem for older head-injured adults on the Golden Stroop, mirroring previous results for normal and diabetic older adult populations as well as Alzheimer patients (Pachana, Marcopulos, Yoash-Gantz, and Thompson, 1995, 1997).