scholarly journals Neuromodulation of Persistent Activity and Working Memory Circuitry in Primate Prefrontal Cortex by Muscarinic Receptors

2021 ◽  
Vol 15 ◽  
Author(s):  
Susheel Vijayraghavan ◽  
Stefan Everling
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Cognitive Control ◽  
Muscarinic Receptors ◽  
Vital Role ◽  
State Transitions ◽  
Brain State ◽  
Persistent Activity ◽  
Memory Representations ◽  
Underlying Mechanisms

Neuromodulation by acetylcholine plays a vital role in shaping the physiology and functions of cerebral cortex. Cholinergic neuromodulation influences brain-state transitions, controls the gating of cortical sensory stimulus responses, and has been shown to influence the generation and maintenance of persistent activity in prefrontal cortex. Here we review our current understanding of the role of muscarinic cholinergic receptors in primate prefrontal cortex during its engagement in the performance of working memory tasks. We summarize the localization of muscarinic receptors in prefrontal cortex, review the effects of muscarinic neuromodulation on arousal, working memory and cognitive control tasks, and describe the effects of muscarinic M1 receptor stimulation and blockade on the generation and maintenance of persistent activity of prefrontal neurons encoding working memory representations. Recent studies describing the pharmacological effects of M1 receptors on prefrontal persistent activity demonstrate the heterogeneity of muscarinic actions and delineate unexpected modulatory effects discovered in primate prefrontal cortex when compared with studies in rodents. Understanding the underlying mechanisms by which muscarinic receptors regulate prefrontal cognitive control circuitry will inform the search of muscarinic-based therapeutic targets in the treatment of neuropsychiatric disorders.

scholarly journals Brain state stability during working memory is explained by network control theory, modulated by dopamine D1/D2 receptor function, and diminished in schizophrenia

2019 ◽  
Author(s):  
Urs Braun ◽  
Anais Harneit ◽  
Giulio Pergola ◽  
Tommaso Menara ◽  
Axel Schaefer ◽  
...  
Keyword(s):  
Working Memory ◽  
Receptor Gene ◽  
D2 Receptor ◽  
Network Control ◽  
D1 Receptor ◽  
Receptor Expression ◽  
State Transitions ◽  
Brain State ◽  
Memory Representations ◽  
The Stability

Dynamical brain state transitions are critical for flexible working memory but the network mechanisms are incompletely understood. Here, we show that working memory entails brain-wide switching between activity states. The stability of states relates to dopamine D1 receptor gene expression while state transitions are influenced by D2 receptor expression and pharmacological modulation. Schizophrenia patients show altered network control properties, including a more diverse energy landscape and decreased stability of working memory representations.

scholarly journals Prefrontal and Parietal Attractor Networks Mediate Working Memory Judgments

2020 ◽  
Author(s):  
Sihai Li ◽  
Christos Constantinidis ◽  
Xue-Lian Qi
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Dorsolateral Prefrontal Cortex ◽  
Critical Role ◽  
Memory Task ◽  
Delayed Response ◽  
Persistent Activity ◽  
Neural Basis ◽  
Brain Areas ◽  
Dorsolateral Prefrontal

ABSTRACTThe dorsolateral prefrontal cortex plays a critical role in spatial working memory and its activity predicts behavioral responses in delayed response tasks. Here we addressed whether this predictive ability extends to categorical judgments based on information retained in working memory, and is present in other brain areas. We trained monkeys in a novel, Match-Stay, Nonmatch-Go task, which required them to observe two stimuli presented in sequence with an intervening delay period between them. If the two stimuli were different, the monkeys had to saccade to the location of the second stimulus; if they were the same, they held fixation. Neurophysiological recordings were performed in areas 8a and 46 of the dlPFC and 7a and lateral intraparietal cortex (LIP) of the PPC. We hypothesized that random drifts causing the peak activity of the network to move away from the first stimulus location and towards the location of the second stimulus would result in categorical errors. Indeed, for both areas, when the first stimulus appeared in a neuron’s preferred location, the neuron showed significantly higher firing rates in correct than in error trials. When the first stimulus appeared at a nonpreferred location and the second stimulus at a preferred, activity in error trials was higher than in correct. The results indicate that the activity of both dlPFC and PPC neurons is predictive of categorical judgments of information maintained in working memory, and the magnitude of neuronal firing rate deviations is revealing of the contents of working memory as it determines performance.SIGNIFICANCE STATEMENTThe neural basis of working memory and the areas mediating this function is a topic of controversy. Persistent activity in the prefrontal cortex has traditionally been thought to be the neural correlate of working memory, however recent studies have proposed alternative mechanisms and brain areas. Here we show that persistent activity in both the dorsolateral prefrontal cortex and posterior parietal cortex predicts behavior in a working memory task that requires a categorical judgement. Our results offer support to the idea that a network of neurons in both areas act as an attractor network that maintains information in working memory, which informs behavior.

scholarly journals Time-invariant working memory representations in the presence of code-morphing in the lateral prefrontal cortex

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Aishwarya Parthasarathy ◽  
Cheng Tang ◽  
Roger Herikstad ◽  
Loong Fah Cheong ◽  
Shih-Cheng Yen ◽  
...  
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Dimensional Subspace ◽  
Neural Data ◽  
Neuronal Populations ◽  
Attractor Model ◽  
Memory Representations ◽  
Low Dimensional ◽  
Types Of Information ◽  
Time Invariant

Abstract Maintenance of working memory is thought to involve the activity of prefrontal neuronal populations with strong recurrent connections. However, it was recently shown that distractors evoke a morphing of the prefrontal population code, even when memories are maintained throughout the delay. How can a morphing code maintain time-invariant memory information? We hypothesized that dynamic prefrontal activity contains time-invariant memory information within a subspace of neural activity. Using an optimization algorithm, we found a low-dimensional subspace that contains time-invariant memory information. This information was reduced in trials where the animals made errors in the task, and was also found in periods of the trial not used to find the subspace. A bump attractor model replicated these properties, and provided predictions that were confirmed in the neural data. Our results suggest that the high-dimensional responses of prefrontal cortex contain subspaces where different types of information can be simultaneously encoded with minimal interference.

scholarly journals Exploring the Inner Workings of Neuron Circuits That Exhibit Persistent Activity To Explain How Working Memory and Executive Function Are Implemented in The Brain

2021 ◽  
Author(s):  
Paul Gomez
Keyword(s):  
Decision Making ◽  
Working Memory ◽  
Prefrontal Cortex ◽  
Executive Function ◽  
Memory Task ◽  
Persistent Activity ◽  
Storage Mechanism ◽  
Minimum Number ◽  
Task Processing ◽  
The Brain

In this research we explore in detail how a phenomenon called sustained persistent activity is achieved by circuits of interconnected neurons. Persistent activity is a phenomenon that has been extensively studied (Papoutsi et al. 2013; Kaminski et. al. 2017; McCormick et al. 2003; Rahman, and Berger, 2011). Persistent activity consists in neuron circuits whose spiking activity remains even after the initial stimuli are removed. Persistent activity has been found in the prefrontal cortex (PFC) and has been correlated to working memory and decision making (Clayton E. Curtis and Daeyeol Lee, 2010). We go beyond the explanation of how persistent activity happens and show how arrangements of those basic circuits encode and store data and are used to perform more elaborated tasks and computations. The purpose of the model we propose here is to describe the minimum number of neurons and their interconnections required to explain persistent activity and how this phenomenon is actually a fast storage mechanism required for implementing working memory, task processing and decision making.

scholarly journals Distributed networks for auditory memory contribute differentially to recall precision

2021 ◽  
Author(s):  
Sung-Joo Lim ◽  
Christiane Thiel ◽  
Bernhard Sehm ◽  
Lorenz Deserno ◽  
Jöran Lepsien ◽  
...  
Keyword(s):  
Working Memory ◽  
Cognitive Control ◽  
Brain Networks ◽  
Temporal Cortex ◽  
Superior Temporal Sulcus ◽  
Brain Regions ◽  
Auditory Memory ◽  
Control Brain ◽  
Memory Representations ◽  
Auditory Objects

AbstractThe representations held in working memory are inherently noisy, but attention directed to relevant objects can effectively enhance their fidelity. While recent working memory models suggest that memory representations are distributed across sensory and cognitive-control brain regions, it remains unknown how multiple brain networks generate this attentional gain in fidelity. Here, we investigated the contributions of the distinct brain networks in maintaining and enhancing memory representations using psychophysical modeling and fMRI. Human listeners performed an auditory syllable pitch-discrimination task, in which they received valid (vs. neutral) retro-active cues to selectively attend to one of the two syllable categories maintained in memory. Valid (vs. neutral) retro-cues facilitated task performance, eliciting faster recall and enhanced recall precision of syllables in memory. Valid retro-cues also led to increased neural activation in fronto-parietal and cingulo-opercular networks, but not in sensory-specific superior temporal cortex. Multivariate pattern analysis as a proxy for representational fidelity in memory revealed that attended syllable objects were maintained in distributed areas across superior temporal, frontal, parietal, and sensorimotor brain areas. However, neural fidelity in left superior temporal sulcus and its enhancement through attention-to-memory best predicted the ensuing individual gain in recall precision of auditory objects from memory. These results demonstrate that maintaining versus attentionally enhancing auditory memory representations are functionally separable mechanisms across distributed brain regions.Significance StatementWorking memory is distributed across sensory and cognitive-control brain regions. But how do these brain networks enhance working memory precision when attention is re-directed to memory? We here investigate the contributions of distinct brain networks in maintaining and enhancing auditory memory representations through attention-to-memory using fMRI. We demonstrate that re-directing attention to the relevant auditory memory objects mainly recruits higher-order cognitive-control networks. Among the multiple brain regions retaining memory representations, however, attentional enhancement of the neural fidelity in superior temporal sulcus best predicts the individual gain in recall precision of auditory objects from memory. This study provides evidence of the interplay among the discrete, functionally specialized brain regions in maintaining and attentionally enhancing working memory representations.

scholarly journals Naturalistic coding of working memory in primate prefrontal cortex

2020 ◽  
Author(s):  
Megan Roussy ◽  
Rogelio Luna ◽  
Lyndon Duong ◽  
Benjamin Corrigan ◽  
Roberto A. Gulli ◽  
...  
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Memory Performance ◽  
Memory Function ◽  
Nmda Receptor Antagonist ◽  
Inhibitory Neurons ◽  
Natural Behavior ◽  
Neuronal Populations ◽  
Memory Representations ◽  
Decoding Accuracy

SummaryThe primate lateral prefrontal cortex (LPFC) is considered fundamental for temporarily maintaining and manipulating mental representations that serve behavior, a cognitive function known as working memory1. Studies in non-human primates have shown that LPFC lesions impair working memory2 and that LPFC neuronal activity encodes working memory representations3. However, such studies have used simple displays and constrained gaze while subjects held information in working memory3, which put into question their ethological validity4,5. Currently, it remains unclear whether LPFC microcircuits can support working memory function during natural behavior. We tested macaque monkeys in a working memory navigation task in a life-like virtual environment while their gaze was unconstrained. We show that LPFC neuronal populations robustly encode working memory representations in these conditions. Furthermore, low doses of the NMDA receptor antagonist, ketamine, impaired working memory performance while sparing perceptual and motor skills. Ketamine decreased the firing of narrow spiking inhibitory interneurons and increased the firing of broad spiking cells reducing population decoding accuracy for remembered locations. Our results show that primate LPFC generates robust neural codes for working memory in naturalistic settings and that such codes rely upon a fine balance between the activation of excitatory and inhibitory neurons.

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