Dopaminergic Modulation of Attentional Selection: Implications for Lexical Access Gabriele Scheler
Department of Computer Science Technical University of Munich D-80290 Munchen
[email protected]
Jean-Marc Fellous Computational Neurobiology Laboratory The Salk Institute for Biological Studies La Jolla, Ca. 92037
[email protected]
Abstract In this paper we present a model of attentional (contextual) selection of verbal information using a spiking neural network model with dopaminergic neuromodulation. The in uence of dopamine on single neurons has been determined from rat prefrontal cortex slices and a modi ed integrate-and- re model has been developed. Dopaminergic modulation allows for the modeling of selection behaviors corresponding to di erent arousal states of the brain. Working memory is modeled here as an interaction of materialindependent executive processes like selection and material-speci c maintenance functions. Verbal selection as well as working memory in general is known to be impaired in low dopaminergic states. In our model we could show that dopamine-modulated conditions allow for a fast and reliable selection processes, while dopaminedepleted conditions tend to create persevering behavior.
1 Introduction Studies on brain imaging have revealed that the task of word generation, such as in a constrained association task ("name a typical verb for a noun"), reliably produces activity in two distinct brain regions: in parietal cortex, the putative storage area for long-term semantic knowledge, and in areas 44 and 45 (Broca's area) in prefrontal cortex (PFC) as sites for attentional selection [3]. Prefrontal activity increases with the diculty of the task. A stereotypical response like "scissors-cut" will generate less activity (and be less impaired in patients with focal damage in left PFC) than a task requiring more suppression of alternatives such as "table-eat" [19]. Similarly, a role of PFC and verbal working memory must be assumed in lexical selection, the task of selecting an appropriate word meaning on the basis of the Part of this research was conducted as a visiting fellow at the Sloan Center for Theoretical Neurobiology, Salk Institute, La Jolla, Ca.
context in which it occurs ('mean' signi es 'average' in the context of mathematics, but 'shabby' when used to describe a person). With a feature-based model of word meaning, this task consists in accessing a word meaning as a constellation of individual features in long-term memory, where certain features are more strongly activated (as part of the dominant or most frequent word meaning) and others de ning alternative meanings are activated less. The process of contextual integration will therefore depend on the selection (enhancement and suppression) of certain features on the basis of previously activated contextual knowledge. Neuroimaging studies of verbal working memory [14] suggest that two distinct regions are involved. Lateral areas of the PFC are activated during the active maintenance (up to 1-2 s) of information for the purpose of manipulation, while dorso-lateral areas (9, 46) are activated for "central executive processes" such as selection, suppression of alternatives and sequential planning. Processes of word meaning selection therefore require the short-term memory storage of several contextual items as well as a selection of relevant information from di erent semantic features. This selection further involves the resolution of competition between retrieved representations. While the exact mechanisms underlying this selection are unknown, information about its time-course are available. Psycholinguistic studies of lexical access [20, 9, 5] have shown that (a) all semantically related meanings are activated during the access of a contextual meaning within a time window of up to 400 ms as shown by semantic priming [9] ("exhaustive access") (b) there may be an initial period during lexical access ( < 200 ms) where only the dominant meaning of a word is accessible, based on ERP data [20]. The role of catecholaminergic neuromodulation on lexical access has been shown indirectly in schizophrenic impairment of contextual selection [2]: instead of retrieving a less frequent, contextually appropriate meaning, schizophrenic patients retrieve the more frequent but contextually irrelevant meaning. This inability to select the appropriate meaning is coupled to a general impairment of attentional selection and a tendency for perseverance as it is documented by performance on the Wisconsin Card Sorting Test, the Stroop [2] and Eriksen [13] tests. Schizophrenia is at least partly characterized by a disturbance of dopamine regulation leading to a low dopaminergic tone and a general hypofrontality [4]. There is a wealth of evidence linking both dopamine and norepinephrine levels in PFC to performance on working memory and attentional selection in di erent species [1], indicating that both very low or very high levels are detrimental to performance. These results suggest that there is an optimal range of dopamine receptor occupancy that allow for short reaction times and few errors in di erent tasks of delayed alternation or delay match-to-sample. We interpret the impairment of contextual integration in schizophrenia as a failure to inhibit dominant feature associations leading to the inability to select relevant associations prompted by the activation of a contextual structure in working memory. A similar theoretical account has been given by [2]. Dopamine modulation in this model involves a gain parameter of a sigmoidal activation function of a ratecoding neuron: i.e. a high dopaminergic state is associated with a steep activation function, and a low dopaminergic state with a shallow one [12]. The architecture of the model consisted of a pool of neurons for word meanings and a di erent pool of neurons for discourse units (contextual information). Bidirectional excitatory connections between these units were responsible for the task of accessing a certain
word meaning in a winner-take-all manner. It could be shown that this ability was compromised for non-modulated neurons, i.e. neurons with a low gain parameter. In the following we shall present a model that is related but di ers in some important respects: (a) we attempt to model the three-stage time course of lexical access, (b) we use a realistic simulation of single-neuron modulation of spiking characteristics, (c) we distinguish between an unspeci c attentional module and speci c task or context representations.
2 The e ect of dopamine modulation on single-neuron properties Dopamine acts on single neurons in prefrontal cortex primarily via two types of receptors, D1-receptors and D2-receptors. A preferential distribution of D1-receptors on excitatory neurons and D2-receptors on inhibitory neurons has been found [7]. The e ect of D1-receptor activation on excitatory (pyramidal) cells in rat PFC has been characterized experimentally in vitro and theoretically in terms of the signal transmission capacity of a single neuron with respect to various types of signals [10]. A modi ed integrate-and- re neuron model for both the unmodulated and the D1-modulated conditions has been developed and can be used in network simulations. Figure 1 shows the e ects of modulation on spike frequency adaptation for a square pulse in the experimental condition and for the simulated neuron. D1-
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Figure 1: Reduction of square-pulse accomodation with D1-modulation A: simulated neurons B: experimental measurements receptor activation induces a G-protein mediated second-messenger process which among other e ects - changes the ecacy of calcium-activated afterhyperpolarizing potassium channels [21]. This means that the temporal dependence of the spiking behavior of a neuron on its internal state is greatly diminished. In essence, a modulated neuron resets quickly, and can process many signals in quick succession faithfully, while the unmodulated neuron shows signal dampening e ects over a period of up to 400 ms. In the latter case, we have signal masking e ects, whereby the strength of a synaptic input required to further induce ring diminishes with the length of the inter-spike interval, while this "relative refractory period" is greatly reduced for a modulated neuron. The temporally varying properties of the single cell are modeled by di erent parameters for resistance (R) and driving force (E ,E2 ), cf. [16]. These parameters capture temporal dependencies of various duration and are thus exible enough to provide a close t to experimental data [10]. The basic
integrate-and- re model is thus augmented as follows:
V = V exp( R(t)t?(1t0+ E (t)) ) ? E (t) 2 with E (t) = E0 exp( t? Et0 ), R(t) = R0 exp( t? Rt0 ), and E2 (t) = E20 exp( t ?Et2f ).
Experimentally determined parameters for the D1-modulated (non-modulated) condition are: = 18:5(16:5) ms, R = 50(50) ms, E = 60(50) ms, R0 = 16(1:8), E0 = ?15:5(?13) mV , E2 = n:a:(9) mv=spike, E2 = n:a:(250) ms, = ?46(?44:5) mV max = n:a:(?36:5) mV . D2-receptor activation increases GABA-ergic activity in prefrontal cortex [8], probably through a depolarization of inhibitory neurons [23]. Furthermore, there is a presynaptic e ect of D2-receptors limiting glutamate eux and reducing the size of excitatory postsynaptic potentials [15]. Inhibitory neurons are usually nonaccomodating and can be adequately modeled by a classic integrate-and- re model. Depolarization and increase in the amount of inhibition can be modeled by a change in ring threshold, while a size reduction of EPSP's as a function of D2-receptor occupancy amounts to a transient reduction of synaptic ecacy. There are considerably more D1-receptors in rat and monkey prefrontal cortex than D2-receptors, and D2-receptors need a much higher level of dopamine to become active [6]. The net e ect of D2-activation is thus an increase of inhibition which serves to stabilize network activity at higher levels of D1-activation.
3 Contextual selection in verbal working memory Working memory tasks such as delay activity (maintenance), inhibition of alternatives and selection of targets (attentional switches) were found to increase dopamine levels in the prefrontal cortex of healthy monkeys [22]. The increase of dopamine may be either due to a short burst of dopamine-producing neurons in the ventral tegmental area (transient response) or to a sustained tonic ring that raises dopamine levels in prefrontal cortex [11]. In our model we simply compare a pathological state of low dopaminergic activity (non-modulated neurons) to a state of raised dopaminergic activity (D1-modulated pyramidal neurons and D2 e ects on inhibition). The discourse-guided adaptation of a word meaning can be modeled as an inhibition of alternatives (similar to constrained association), where a dominant word meaning is initially available and a switching to a new representation - involving suppression of the dominant meaning - has to be performed. A compromised attentional system, which has non-modulated neurons, i.e. a lack of dopamine in the prefrontal cortex, will fail to provide this fast contextual switch in all cases. The model consists of two separate pools of neurons corresponding to left inferior and dorsolateral PFC implementing verbal working memory (WM) and central executive functions respectively. A word meaning is represented as a set of features, where each dominant feature is surrounded by a number of alternative features and a structure of lateral inhibition prevails among competing features. There is an "attentional module" consisting of a pool of neurons with unspeci c connections to the working memory representation and a number of contextual units with a speci c pattern of excitatory connections to features of the target word. Working memory and attentional modules are linked by feedback connections (Fig. 2A). Initial activation of the dominant word meaning is maintained in an attractor-like reverberant
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Figure 2: A: Model architecture - left: verbal WM right: attentional module. Small circles - inhibitory neurons, lled circles - contextual units, dotted lines - inhibitory links, straight lines- excitatory links. On the right side, inhibitory neurons are not explicitly shown. B: Spiking activity for unmodulated neurons with strong input and strong synaptic weights state that is fairly stable against background noise or unspeci c input such as from the attentional module. A switch within a feature constellation is initiated by an external input to the attentional module. Throughout a period of about 200 ms activation in verbal WM rises due to the positive feedback loop with the attentional module obliterating the dominant feature representation and leading to a state of generally activated features (Fig. 3 A). The activation of speci c contextual units then boosts the activity of a selected feature attractor and inhibits the activity of unspeci c attentional neurons. A new single attractor is then present in verbal WM (Fig. 3 A). This process is compromised when dopaminergic modulation is reduced
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Figure 3: Contextual Feature Selection in verbal WM. A: with DA-modulation B: no DA-modulation. The dominant (initial) attractor is shown in front, the contextually selected one in the middle. 3 features are shown. (using the non-modulated set of parameters for excitatory neurons). (Fig. 3 B). This di erence is due to the changed information transmission properties of the single neurons involved. Modulated neurons reset quickly and are thus able to keep up a high ring rate and an initial synchronization of ring within a positive feedback loop. Unmodulated neurons have a signal dampening e ect due to an extended period of diminished excitability and a reduction of synchronicity due to a lower re-
liability of ring within that time. We can see that this e ect is independent of the strength of the outside inputs or the strength of synaptic weights within the network. If we try di erent weights for the feedback connection, a synchronized feedback oscillation never develops with strongly accomodating (unmodulated) neurons. I.e. it becomes speci cally dicult to achieve fast transitions between attractors, because neurons follow an all-or-none principle of strong activity followed by insensitivity to new input (Fig. 2 B). These results predict that schizophrenics should be impaired on verbal association tasks where selection is highly constrained. They should also show no semantic priming e ects for non-dominant, non-selected meanings. In our model, it is not only the contextual selection of an appropriate meaning is disturbed but also the preliminary state of de-activation of the dominant meaning. The persevering behavior does not result from the inability to perform a switch of representation, but rather it is due to a speci c inability of unlocking the dominant state. This hypothesis is consistent with comparable behavior on the Stroop task [18] and may be veri ed by reaction time tests or control of eye movements during the resolution of discourse ambiguities [17].
4 Conclusion We have presented a neural network model of contextual selection that uses integrate-and- re neurons subjected to the dopaminergic modulation of their spiking characteristics. Using this type of model neuron, we have built a two-module network consisting of a short-term storage device and a central executive function network which implements the function of directing attention. The functioning of contextual selection depends on a speci c dopaminergic tone that corresponds to an optimal activation of D1-receptors and their counterbalance by D2-receptors. This dopaminergic tone results in speci c temporal signal processing characteristics of single neurons. We could show that the function of selective contextual access and suppression of alternatives depends on these neuronal properties. Speci c impairments in word meaning access observed in schizophrenics and attributed to the general low dopaminergic tone in prefrontal cortex can thus be explained by the given model.
References
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