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(Medical Xpress)—Translating stored information into behaviorally appropriate responses is a pretty fundamental brain activity, supporting biological, social and survival behaviors. Researchers have long believed that the lateral prefrontal cortex (PFC) is a hub of the working memory system, but haven't yet been able to establish whether working memory is supported by a single distributed network or if multiple specialized networks in the PFC express working memory function.

In order to establish the network structure of a working memory task, a group of researchers at New York University made neuronal recordings of the arcuate gyruses of two macaque monkeys engaged in either a memory-guided or visually guided oculomotor delayed response (ODR) task. They subsequently analyzed the recordings to determine whether the networks involved in working memory contained components with different identifiable functions. They have published their results in the Proceedings of the National Academy of Sciences.

The work is important, because many neuropsychiatric disorders are characterized by degraded working memory function; establishing the network basis for such disorders could point toward therapeutic interventions.

The study establishes that working memory nodes are mapped to specific anatomical regions. Two of these network modes encode early and late forms of information storage; the third encodes response preparation. They also uncovered a previously unknown distinction between storage and response modes of persistent brain activity—these modes display different functions, have different anatomical patterns, and exhibit distinct patterns of firing and the coordination of spike timing.

The response network is identified in the study with a preparatory process because it exhibited a delay following stimulus before neuronal firing occurred. However, the researchers note, "the response population identified here might not exclusively mediate response preparation and may also be involved in response selection." They add that the task design itself may not be able to distinguish between different response-related activities.

Across the studied anatomical domain, the researchers found that the storage and response networks were prevalent at different topographic locations and depths of the PFC, which is notable due to its contrast with the findings of previous studies. The note that "a difference of only a few millimeters in recording location was critical to finding this network in PFC."

A temporal analysis revealed a precisely organized phase lag between action potentials from the storage and response networks, which could be a mechanism for coordinating memory storage and contingent responses. The researchers posit that the brain uses coherent activity in order to process behavior dependent on both past stimulus and rule-based responses.

The researchers conclude that the study's results indicate that the impairments in memory-guided behavior that characterize neuropsychiatric disorders could arise from disrupted response preparation rather than disrupted storage, as commonly believed. "Therefore, it is plausible that pharmacologic agents used in the treatment of working memory disorders act primarily by counteracting degraded activity in the response network," they write, noting that future work is needed to test the linkage between dopaminergic brain function and network activity in the PFC.

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More information: "Multiple component networks support working memory in prefrontal cortex." PNAS 2015 ; published ahead of print August 17, 2015, "Multiple component networks support working memory in prefrontal cortex."2015 ; published ahead of print August 17, 2015, DOI: 10.1073/pnas.1504172112 Abstract

Lateral prefrontal cortex (PFC) is regarded as the hub of the brain's working memory (WM) system, but it remains unclear whether WM is supported by a single distributed network or multiple specialized network components in this region. To investigate this problem, we recorded from neurons in PFC while monkeys made delayed eye movements guided by memory or vision. We show that neuronal responses during these tasks map to three anatomically specific modes of persistent activity. The first two modes encode early and late forms of information storage, whereas the third mode encodes response preparation. Neurons that reflect these modes are concentrated at different anatomical locations in PFC and exhibit distinct patterns of coordinated firing rates and spike timing during WM, consistent with distinct networks. These findings support multiple component models of WM and consequently predict distinct failures that could contribute to neurologic dysfunction. Journal information: Proceedings of the National Academy of Sciences

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