While extracellular somatic action potentials from freely moving rats have been well characterized, axonal activity has not. We report direct extracellular tetrode recordings of putative axons whose principal feature is a short duration waveform (SDW) with an average peak-trough length less than 179 μs. While SDW recordings using tetrodes have previously been treated as questionable or classified as cells, we hypothesize that they are representative of axonal activity. These waveforms have significantly shorter duration than somatic action potentials, are triphasic and are therefore similar to classic descriptions of microelectrode recordings in white matter and of in vitro action potential propagation along axons. We describe SDWs recorded from pure white-matter tracts including the alveus and corpus callosum. Recordings of several SDWs in the alveus exhibit grid-like firing patterns suggesting these axons carry spatial information from entorhinal cortical neurons. Finally, we locally injected the GABAA agonist Muscimol into layer CA1 of the hippocampus while simultaneously recording somatic activity and SDWs on the same tetrodes. The persistent activity of SDWs during Muscimol inactivation of somatic action potentials indicates that SDWs are representative of action potential propagation along axons projecting from more distal somata. This characterization is important as it illustrates the dangers of exclusively using spike duration as the sole determinant of unit type, particularly in the case of interneurons whose peak-trough times overlap with SDWs. It may also allow future studies to explore how axonal projections from disparate brain regions integrate spatial information in the hippocampus, and provide a basis for studying the effects of pharmaceutical agents on signal transmission in axons, and ultimately to aid in defining the potential role of axons in cognition.
Epilepsy is often associated with cognitive and behavioral impairments that can have profound impact on the quality of life of patients. Although the mechanisms of cognitive impairment are not completely understood, we make an attempt to describe, from a systems perspective, how information processing is affected in epilepsy disorders. The aim of this review is to (1) define the nature of cognitive deficits associated with epilepsy, (2) review fundamental systems-level mechanisms underlying information processing, and (3) describe how information processing is dysfunctional in epilepsy and investigate the relative contributions of etiology, seizures, and interictal discharges (IDs). We conclude that these mechanisms are likely to be important and deserve more detailed scrutiny in the future.T he epilepsies are a group of disorders defined by the propensity for an individual to have epileptic seizures (Fisher et al. 2014). In addition to seizures, these common and serious neurological disorders are associated with cognitive and behavioral impairments (Berg and Scheffer 2011). The cognitive and behavioral impairments are critical determinants of the reductions in quality of life observed in patients with epilepsy (Ronen et al. 2003;Loring et al. 2004). It is, therefore, of major importance that the mechanisms underlying cognitive impairments are characterized as this is likely to lead to novel interventions that will ultimately improve the quality of life of people with epilepsy. Epilepsy is associated with a variety of physiological and molecular alterations at the level of changes in the genome, gene expression, receptor characteristics, peptides, and brain injury. These changes are not only responsible for seizures but also for functional abnormalities underlying cognitive impairment. It is likely that several of these mechanisms are occurring in concert, and, therefore, it is important to study the net effects of these alterations at the level of neural networks as this may also lead to novel interventions that could improve outcomes. The aims of this article are to (1) define the nature of cognitive deficits associated with epilepsy, (2) review fundamental systems-level mechanisms underlying information processing, and (3) describe how information processing is dysfunctional in epilepsy and investigate the relative contributions of etiology, seizures, and interictal discharges (IDs).
Summary Purpose: There is still controversy in deciding which patients with frontal lobe epilepsy (FLE) should undergo resective surgery, even though it is a well‐established therapy. The aim of this study is to define multiple outcome measures and determine whether there are certain subpopulations of preferred surgical candidates that have a more favorable seizure prognosis. Methods: Fifty‐eight patients underwent resective FLE surgery with a mean follow‐up period of 79.3 months (range 12–208 months). Patient demographics, clinical seizure characteristics, seizure‐onset zone within the frontal lobes, and diagnostic tests were tabulated. Engel class, International League Against Epilepsy (ILAE) class, postoperative seizure patterns, time to first recurrent seizure, and seizures and employment during the last year of follow‐up were used as outcome measures. Neuropsychological performance and Beck Depression Inventory (BDI) scores were used to define neuropsychological outcome and examined as predictors of seizure outcome. Key Findings: Thirty‐three (57%) patients with resective surgery had an Engel class I outcome and 29 (50%) had an ILAE class I outcome. Mean time to first seizure after surgery was 33.3 months (range 0–208). Only 14 patients (24%) were completely seizure‐free without auras (Engel IA) throughout the entire follow‐up period. The most common pattern of seizure recurrence was mixed, with prolonged periods of seizure freedom intermixed with recurrences. In addition, 32% of patients made gains in employment and 52% were able to reduce use of antiepileptic drugs (AEDs), although only 9% discontinued AEDs. No significant association was found between class I or class IA outcome and the presence of a focal magnetic resonance imaging (MRI) abnormality, any specific localization of seizure focus within the frontal lobe, or neuropsychological change. Significance: Findings indicate that that long‐term outcome is generally favorable in FLE resective surgery, and support the need for considering multiple outcome measures to more fully characterize clinically relevant postsurgical changes. Outcome can be favorable even in MRI‐negative patients.
With their ‘all-or-none’ action potential responses, single neurons (or units) are accepted as the basic computational unit of the brain. There is extensive animal literature to support the mechanistic importance of studying neuronal firing as a way to understand neuronal microcircuits and brain function. Although most studies have emphasized physiology, there is increasing recognition that studying single units provides novel insight into system level mechanisms of disease. Microelectrode recordings are becoming more common in humans, paralleling the increasing use of intracranial electroencephalography recordings in the context of presurgical evaluation in focal epilepsy. In addition to single unit data, microelectrode recordings also record local field potentials and high frequency oscillations, some of which may be different to that recorded by clinical macroelectrodes. However, microelectrodes are being used almost exclusively in research contexts and there are currently no indications for incorporating microelectrode recordings into routine clinical care. In this review, we summarise the lessons learnt from 65 years of microelectrode recordings in human epilepsy patients. We cover the electrode constructs that can be utilised, principles of how to record and process microelectrode data as well as insights into ictal dynamics, interictal dynamics and cognition. We end with a critique on the possibilities of incorporating single unit recordings into clinical care, with a focus on potential clinical indications, each with their specific evidence base and challenges.
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