The Effect of Dopamine on Working Memory (original) (raw)
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Dopamine modulation in the basal ganglia locks the gate to working memory
Journal of Computational Neuroscience, 2006
The prefrontal cortex and basal ganglia are deeply implicated in working memory. Both structures are subject to dopaminergic neuromodulation in a way that exerts a critical influence on the proper operation of working memory. We present a novel network model to elucidate the role of phasic dopamine in the interaction of these two structures in initiating and maintaining mnemonic activity. We argue that neuromodulation plays a critical role in protecting memories against both internal and external sources of noise. Increases in cortical gain engendered by prefrontal dopamine release help make memories robust against external distraction, but do not offer protection against internal noise accompanying recurrent cortical activity. Rather, the output of the basal ganglia provides the gating function of stabilization against noise and distraction by enhancing select memories through targeted disinhibition of cortex. Dopamine in the basal ganglia effectively locks this gate by influencing the stability of Action editor: up and down states in the striatum. Dopamine's involvement in affective processing endows this gating with specificity to motivational salience. We model a spatial working memory task and show that these combined effects of dopamine lead to superior performance.
A neurocomputational theory of the dopaminergic modulation of working memory functions
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1999
The dopaminergic modulation of neural activity in the prefrontal cortex (PFC) is essential for working memory. Delay-activity in the PFC in working memory tasks persists even if interfering stimuli intervene between the presentation of the sample and the target stimulus. Here, the hypothesis is put forward that the functional role of dopamine in working memory processing is to stabilize active neural representations in the PFC network and thereby to protect goal-related delay-activity against interfering stimuli. To test this hypothesis, we examined the reported dopamine-induced changes in several biophysical properties of PFC neurons to determine whether they could fulfill this function. An attractor network model consisting of model neurons was devised in which the empirically observed effects of dopamine on synaptic and voltage-gated membrane conductances could be represented in a biophysically realistic manner. In the model, the dopamine-induced enhancement of the persistent Na+...
Dopamine Alters the Fidelity of Working Memory Representations according to Attentional Demands
Journal of Cognitive Neuroscience, 2017
Capacity limitations in working memory (WM) necessitate the need to effectively control its contents. Here, we examined the effect of cabergoline, a dopamine D2 receptor agonist, on WM using a continuous report paradigm that allowed us to assess the fidelity with which items are stored. We assessed recall performance under three different gating conditions: remembering only one item, being cued to remember one target among distractors, and having to remember all items. Cabergoline had differential effects on recall performance according to whether distractors had to be ignored and whether mnemonic resources could be deployed exclusively to the target. Compared with placebo, cabergoline improved mnemonic performance when there were no distractors but significantly reduced performance when distractors were presented in a precue condition. No significant difference in performance was observed under cabergoline when all items had to be remembered. By applying a stochastic model of respo...
International journal of neural systems, 2010
How do organisms select and organize relevant sensory input in working memory (WM) in order to deal with constantly changing environmental cues? Once information has been stored in WM, how is it protected from and altered by the continuous stream of sensory input and internally generated planning? The present study proposes a novel role for dopamine (DA) in the maintenance of WM in the prefrontal cortex (Pfc) neurons that begins to address these issues. In particular, DA mediates the alternation of the Pfc network between input-driven and internally-driven states, which in turn drives WM updates and storage. A biologically inspired neural network model of Pfc is formulated to provide a link between the mechanisms of state switching and the biophysical properties of Pfc neurons. This model belongs to the recurrent competitive fields(33) class of dynamical systems which have been extensively mathematically characterized and exhibit the two functional states of interest: input-driven a...
Working memory is responsible for the temporary manipulation and storage of information to support reasoning, learning and comprehension in the human brain. Background oscillations from subcortical structures may drive a gating or switching mechanism during working memory computations, and different frequency bands may be associated with different processes while working memory tasks are performed. There are three well-known relationships between working memory processes and specific frequency bands of subcortical oscillations, namely: the storage of new information which correlates positively with beta/gamma-frequency band oscillations, the maintenance of information while ignoring irrelevant stimulation which is directly linked to theta-frequency band oscillations, and the clearance of memory which is associated with alpha-frequency band oscillations. Although these relationships between working memory processes and subcortical background oscillations have been observed, a full explanation of these phenomena is still needed. This paper will aid understanding of the working memory’s operation and phase switching by proposing a novel and biophysical realistic mathematical-computational framework which unifies the generation of subcortical background oscillations, the role of basal ganglia-thalamo-cortical circuits and the influence of dopamine in the selection of working memory operations and phases: this has never been attempted before.
Dopamine and the regulation of cognition and attention
Progress in neurobiology, 2002
Dopamine (DA) acts as a key neurotransmitter in the brain. Numerous studies have shown its regulatory role for motor and limbic functions. However, in the early stages of Parkinson's disease (PD), alterations of executive functions also suggest a role for DA in regulating cognitive functions. Some other diseases, which can also involve DA dysfunction, such as schizophrenia or attention deficit hyperactivity disorder (ADHD) in children, as shown from the ameliorative action of dopaminergic antagonists and agonists, respectively, also show alteration of cognitive functions. Experimental studies showed that selective lesions of the dopaminergic neurons in rats or primates can actually provide cognitive deficits, especially when the mesocorticolimbic component of the dopaminergic systems is altered. Data from the experiments also showed significant alteration in attentional processes, thus raising the question of direct involvement of DA in regulating attention. Since the dopaminergic influence is mainly exerted over the frontal lobe and basal ganglia, it has been suggested that cognitive deficits express alteration in these subcortical brain structures closely linked to cortical areas, more than simple deficit in dopaminergic transmission. This point is still a matter of debate but, undoubtedly, DA acts as a powerful regulator of different aspects of cognitive brain functions. In this respect, normalizing DA transmission will contribute to improve the cognitive deficits not only related to neurologic or psychiatric diseases, but also in normal aging. Ontogenic and phylogenetic analysis of dopaminergic systems can provide evidences for a role of DA in the development of cognitive general capacities. DA can have a trophic action during maturation, which may influence the later cortical specification, particularly of pre-frontal cortical areas. Moreover, the characteristic extension of the dopaminergic cortical innervation in the rostro-caudal direction during the last stages of evolution in mammals can also be related to the appearance of progressively more developed cognitive capacities. Such an extension of cortical DA innervation could be related to increased processing of cortical information through basal ganglia, either during the course of evolution or development. DA has thus to be considered as a key neuroregulator which contributes to behavioral adaptation and to anticipatory processes necessary for preparing voluntary action consequent upon intention. All together, it can be suggested that a correlation exists between DA innervation and expression of cognitive capacities. Altering the dopaminergic transmission could, therefore, contribute to cognitive impairment.
bioRxiv (Cold Spring Harbor Laboratory), 2023
Working memory is considered as the scratchpad to write, read, and process information to perform cognitive tasks. Basal Ganglia (BG) and Prefrontal Cortex are two important parts of the brain that are involved in working memory functions and both the structures receive projections from dopaminergic nuclei. In this modelling study, we specifically focus on modelling the working memory functions of the BG, the working memory deficits in Parkinson's disease conditions, and the impact of dopamine deficiency on different kinds of working memory functions. Though there are many experimental and modelling studies of working memory properties, there is a paucity of models of the BG that provide insights into the contributions of the BG in working memory functions. The proposed model of the BG is a unified model that can explain the working memory functions of the BG over a wide variety of tasks in normal and Parkinson's disease conditions.
Dopamine Modulation in a Basal Ganglio-Cortical Network Implements Saliency-Based Gating of
Dopamine exerts two classes of effect on the sustained neural activity in prefrontal cortex that underlies working memory. Direct release in the cortex increases the contrast of prefrontal neurons, enhancing the robustness of storage. Release of dopamine in the striatum is associated with salient stimuli and makes medium spiny neurons bistable; this modulation of the output of spiny neurons affects prefrontal cortex so as to indirectly gate access to working memory and additionally damp sensitivity to noise. Existing models have treated dopamine in one or other structure, or have addressed basal ganglia gating of working memory exclusive of dopamine effects. In this paper we combine these mechanisms and explore their joint effect. We model a memory-guided saccade task to illustrate how dopamine's actions lead to working memory that is selective for salient input and has increased robustness to distraction.
A dopamine gradient controls access to distributed working memory in monkey cortex
2020
SummaryDopamine is critical for working memory. However, its effects throughout the large-scale primate cortex are poorly understood. Here we report that dopamine receptor density per neuron, measured by receptor autoradiography in the macaque monkey cortex, displays a macroscopic gradient along the cortical hierarchy. We developed a connectome- and biophysically-based model for distributed working memory that incorporates multiple neuron types and a dopamine gradient. The model captures an inverted U-shaped dependence of working memory on dopamine. The spatial distribution of mnemonic persistent activity matches that observed in over 90 experimental studies. We show that dopamine filters out irrelevant stimuli by enhancing inhibition of pyramidal cell dendrites. The level of cortical dopamine can also determine whether memory encoding is through persistent activity or an internal synaptic state. Taken together, our work represents a cross-level understanding that links molecules, c...
The Journal of Neuroscience, 2018
Dopamine (DA) modulates corticostriatal connections. Studies in which imaging of the DA system is integrated with functional imaging during cognitive performance have yielded mixed findings. Some work has shown a link between striatal DA (measured by PET) and fMRI activations, whereas others have failed to observe such a relationship. One possible reason for these discrepant findings is differences in task demands, such that a more demanding task with greater prefrontal activations may yield a stronger association with DA. Moreover, a potential DA-BOLD association may be modulated by task performance. We studied 155 (104 normal-performing and 51 lowperforming) healthy older adults (43% females) who underwent fMRI scanning while performing a working memory (WM) n-back task along with DA D 2/3 PET assessment using [ 11 C]raclopride. Using multivariate partial-least-squares analysis, we observed a significant pattern revealing positive associations of striatal as well as extrastriatal DA D 2/3 receptors to BOLD response in the thalamo-striatalcortical circuit, which supports WM functioning. Critically, the DA-BOLD association in normal-performing, but not low-performing, individuals was expressed in a load-dependent fashion, with stronger associations during 3-back than 1-/2-back conditions. Moreover, normal-performing adults expressing upregulated BOLD in response to increasing task demands showed a stronger DA-BOLD association during 3-back, whereas low-performing individuals expressed a stronger association during 2-back conditions. This pattern suggests a nonlinear DA-BOLD performance association, with the strongest link at the maximum capacity level. Together, our results suggest that DA may have a stronger impact on functional brain responses during more demanding cognitive tasks.