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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...

Prior to a joint meeting of the Neurodiab Association and International Symposium on Diabetic Neuropathy held in Toronto, Ontario, Canada, 13-18 October 2009, Solomon Tesfaye, Sheffield, UK, convened a panel of neuromuscular experts to provide an update on polyneuropathies associated with diabetes (Toronto Consensus Panels on DPNs, 2009). Herein, we provide definitions of typical and atypical diabetic polyneuropathies (DPNs), diagnostic criteria, and approaches to diagnose sensorimotor polyneuropathy as well as to estimate severity. Diabetic sensorimotor polyneuropathy (DSPN), or typical DPN, usually develops on long-standing hyperglycaemia, consequent metabolic derangements and microvessel alterations. It is frequently associated with microvessel retinal and kidney disease-but other causes must be excluded. By contrast, atypical DPNs are intercurrent painful and autonomic small-fibre polyneuropathies. Recognizing that there is a need to detect and estimate severity of DSPN validly and reproducibly, we define subclinical DSPN using nerve conduction criteria and define possible, probable, and confirmed clinical levels of DSPN. For conduct of epidemiologic surveys and randomized controlled trials, it is necessary to pre-specify which attributes of nerve conduction are to be used, the criterion for diagnosis, reference values, correction for applicable variables, and the specific criterion for DSPN. Herein, we provide the performance characteristics of several criteria for the diagnosis of sensorimotor polyneuropathy in healthy subject- and diabetic subject cohorts. Also outlined here are staged and continuous approaches to estimate severity of DSPN.

Abstract-Objective:This assessment evaluates the clinical utility, efficacy, and safety of quantitative sensory testing (QST). Methods: By searching MEDLINE, Current Contents, and their personal files, the authors identified 350 articles. Selected articles utilized computer operated threshold systems, manually operated threshold systems, and electrical threshold devices. The authors evaluated the use of normal values and the degree of reproducibility between the same and different systems. Articles were rated using a standard classification of evidence scheme. Results: Because of differences between systems, normal values from one system cannot be transposed to others. Reproducibility of results was also an important concern, and there is no consensus on how it should be defined. The authors identified no adequately powered class I studies demonstrating the effectiveness of QST in evaluating any particular disorder. A number of class II and III studies demonstrated that QST is probably or possibly useful in identifying small or large fiber sensory abnormalities in patients with diabetic neuropathy, small fiber neuropathies, uremic neuropathies, and demyelinating neuropathy. Conclusions: QST is a potentially useful tool for measuring sensory impairment for clinical and research studies. However, QST results should not be the sole criteria used to diagnose pathology. Because malingering and other nonorganic factors can influence the test results, QST is not currently useful for the purpose of resolving medicolegal matters. Well-designed studies comparing different QST devices and methodologies are needed and should include patients with abnormalities detected solely by QST. NEUROLOGY 2003;60:898 -904 Quantitative sensory testing (QST) systems have been developed to assess and quantify sensory function in patients with neurologic symptoms or in those at risk of developing neurologic disease. QST measures the detection threshold of accurately calibrated sensory stimuli. Vibratory, thermal, or painful stimuli are often chosen because they relate to distinct neuroanatomic pathways with discrete fiber populations.1-3 It should be appreciated, however, that natural stimuli rarely activate single types of receptors but rather activate different combinations of receptors. 1Quantitative sensory tests are psychophysical in nature, requiring cooperation from the patient. While the sensory stimulus is an objective physical event, the response represents the subjective report from a patient or control subject. If abnormal, the result may signal dysfunction anywhere along the sensory pathway between the receptor apparatus, the primary sensory cortex, and the association cortex. Furthermore, psychological factors figure prominently in sensory function perception. Thus, QST differs from nerve conduction and evoked potential testing in which the stimulus generates an evoked response that is generally independent of cooperation from the subject. 4QST devices. QST systems are separable into devices that generate specific physical...

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Auditory stream segregation refers to the organization of sequential sounds into "perceptual streams" reflecting individual environmental sound sources. In the present study, sequences of alternating high and low tones, "...ABAB...," similar to those used in psychoacoustic experiments on stream segregation, were presented to awake monkeys while neural activity was recorded in primary auditory cortex (A1). Tone frequency separation (AF), tone presentation rate (PR), and tone duration (TD) were systematically varied to examine whether neural responses correlate with effects of these variables on perceptual stream segregation. "A" tones were fixed at the best frequency of the recording site, while "B" tones were displaced in frequency from "A" tones by an amount = delta F. As PR increased, "B" tone responses decreased in amplitude to a greater extent than "A" tone responses, yielding neural response patterns dominated by "A" tone responses occurring at half the alternation rate. Increasing TD facilitated the differential attenuation of "B" tone responses. These findings parallel psychoacoustic data and suggest a physiological model of stream segregation whereby increasing delta F, PR, or TD enhances spatial differentiation of "A" tone and "B" tone responses along the tonotopic map in A1.

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