Working memory refers to the ability of the brain to store and manipulate information over brief time periods, ranging from seconds to minutes. As opposed to long-term memory, which is critically dependent upon hippocampal processing, critical substrates for working memory are distributed in a modality-specific fashion throughout cortex. N-methyl-D-aspartate (NMDA) receptors play a crucial role in the initiation of long-term memory. Neurochemical mechanisms underlying the transient memory storage required for working memory, however, remain obscure. Auditory sensory memory, which refers to the ability of the brain to retain transient representations of the physical features (e.g., pitch) of simple auditory stimuli for periods of up to approximately 30 sec, represents one of the simplest components of the brain working memory system. Functioning of the auditory sensory memory system is indexed by the generation of a well-defined event-related potential, termed mismatch negativity (MMN). MMN can thus be used as an objective index of auditory sensory memory functioning and a probe for investigating underlying neurochemical mechanisms. Monkeys generate cortical activity in response to deviant stimuli that closely resembles human MMN. This study uses a combination of intracortical recording and pharmacological micromanipulations in awake monkeys to demonstrate that both competitive and noncompetitive NMDA antagonists block the generation of MMN without affecting prior obligatory activity in primary auditory cortex. These findings suggest that, on a neurophysiological level, MMN represents selective current flow through open, unblocked NMDA channels. Furthermore, they suggest a crucial role of cortical NMDA receptors in the assessment of stimulus familiarity/unfamiliarity, which is a key process underlying working memory performance.Working memory refers to the ability of the brain to store and manipulate information over brief time periods, ranging from seconds to minutes. As compared with long-term memory, which is critically dependent upon hippocampal long-term potentiation, critical substrates for working memory are distributed in a modality specific fashion throughout cortex (1, 2). On a neurophysiological level, working memory has been linked to transient, task-related alterations in the firing rates of neurons in modality-specific brain regions, permitting the use of intracortical recordings to investigate neurochemical mechanisms underlying functioning of the brain working memory system (3-5).Cortical information processing is critically dependent upon the interplay between glutamatergic and y-aminobutyric acid (GABA)ergic neurotransmission. Glutamate is the primary excitatory amino transmitter in mammalian cortex, being present in approximately 60% of cortical neurons and 100% of cortical pyramidal neurons. Glutamatergic fibers mediate all thalamocortical and corticortical projections within cortex, as well as corticofugal projections from cortex to subcortical structures. Within cortex, the interplay...

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The human superior temporal cortex plays a critical role in hearing, speech, and language, yet its functional organization is poorly understood. Evoked potentials (EPs) to auditory click‐train stimulation presented binaurally were recorded chronically from penetrating electrodes implanted in Heschl's gyrus (HG), from pial‐surface electrodes placed on the lateral superior temporal gyrus (STG), or from both simultaneously, in awake humans undergoing surgery for medically intractable epilepsy. The distribution of averaged EPs was restricted to a relatively small area on the lateral surface of the posterior STG. In several cases, there were multiple foci of high amplitude EPs lying along this acoustically active portion of STG. EPs recorded simultaneously from HG and STG differed in their sensitivities to general anesthesia and to changes in rate of stimulus presentation. Results indicate that the acoustically active region on the STG is a separate auditory area, functionally distinct from the HG auditory field(s). We refer to this acoustically sensitive area of the STG as the posterior lateral superior temporal area (PLST). Electrical stimulation of HG resulted in short‐latency EPs in an area that overlaps PLST, indicating that PLST receives a corticocortical input, either directly or indirectly, from HG. These physiological findings are in accord with anatomic evidence in humans and in nonhuman primates that the superior temporal cortex contains multiple interconnected auditory areas. J. Comp. Neurol. 416:79–92, 2000. © 2000 Wiley‐Liss, Inc.

The current study assessed the normal development of cortical auditory evoked potentials (CAEPs) in humans presented with pure tone stimuli at relatively fast stimulus rates. Traditionally, maturation of sound processing indexed by CAEPs has been studied in paradigms using inter-stimulus intervals (ISIs) generally slower than 1 Hz. While long ISIs may enhance the amplitude of CAEP components, speech information generally occurs at more rapid rates. These slower rates of sound presentation may not accurately assess auditory cortical functions in more realistic sound environments. We examined the effect of temporal rate on the elicitation of the P1-N1-P2-N2 components to unattended sounds at four levels of stimulus onset asynchrony (SOA, onset to onset, 200, 400, 600, and 800 ms) in children grouped separately by year (ages 8, 9, 10, 11 years), in adolescents (age 16 years) and in one group of young adults (ages 22-40 years). We found that both age and stimulus rate produced profound changes in CAEP morphology. Between the ages of 8-11 years, the P1 and N2 components dominated the ERP waveform at all stimulus rates. N1, the dominant CAEP component in adults, appeared as a bifurcation in a broad positive peak at earlier ages, and did not emerge as a separate component until adolescence. While the P1-N1-P2 components are more "adult-like" than "child-like" in the adolescent subjects, the N2 component, a hallmark of the child obligatory response, was still present. Faster rates resulted in the suppression of discrete components such that by 200 ms, only P1 in the adults and adolescents, and both P1 and N2 in the youngest children were discernable. We conclude that both age and ISI are important variables in the assessment of auditory cortex function and maturation. The presence of N2 in adolescents indicates that auditory cortical maturation persists into teen years.