PubMed Health⌕ Search

Biomedical subjects

Charles L Wilson

Publications and source records attributed to Charles L Wilson.

At least 19 recordsLinked to original sources
PubMed2007

Characterizing interneuron and pyramidal cells in the human medial temporal lobe in vivo using extracellular recordings.

The goal of this study was to characterize the electrophysiological features of single neurons recorded deep within the medial temporal lobes in humans. Using three physiological criteria to distinguish principal cells and interneurons (firing rate, burst propensity, and action potential waveform) and a large data set of human single neurons (585) from thirteen patients, we show that single neurons in the human MTL separate into two distinct classes comparable to the pyramidal cell and interneuron classes described in animals. We also find that the four different MTL brain regions that we examined (amygdala, hippocampus, entorhinal cortex, and posterior parahippocampal cortex) show unique action potential characteristics, which may in turn relate to the role that neurons from these regions play in behavior. A subset of cells were recorded while patients engaged in both slow-wave (SWS) and rapid-eye movement (REM) sleep and a comparison of the electrophysiological features during these different sleep stages showed that interneurons tended to burst more during SWS compared to REM, while only principal cells in the EC and hippocampus showed a greater propensity for bursting during SWS. Together, our results support the idea that human single neurons have electrophysiologically identifiable cell types, similar to those observed in other mammals, and provide insight into regional and functional differences in spike-wave characteristics relevant to considerations about neural populations in the human brain.

Action Potentials↗
PubMed2006

Changes in extracellular glutamate levels in rat orbitofrontal cortex during sleep and wakefulness.

BACKGROUND: Functional neuroimaging studies have shown that limbic and paralimbic areas display increased activity during REM sleep when compared to wakefulness. This increase in limbic activity is specific to the REM period of sleep. PET scanners do not provide a neurochemical explanation for this increased activity during REM sleep. In order to better understand the neurochemical basis of this increase, extracellular glutamate levels were measured in the rat orbitofrontal cortex during the stages of sleep and wakefulness. METHODS: EEG and EMG activity were registered to score the behavioral state in epochs of 15 sec into three stages: wakefulness, non-REM sleep and rapid eye movement (REM) sleep. To correlate the glutamate concentration of the orbitofrontal cortex with sleep-wake states, 1-min dialysate samples were taken and classified as wakefulness, non-REM or REM sleep if all four of the 15-sec epochs occurring during the collection of that sample and after correction for dead time corresponded to the respective state. High-performance liquid chromatography (HPLC) with electrochemical detection was used to measure glutamate levels. RESULTS: Glutamate levels of the orbitofrontal cortex were increased during REM sleep, diminished during wakefulness, and the lowest levels were found during non-REM sleep. CONCLUSIONS: These findings demonstrate an increase in the concentration of the excitatory neurotransmitter glutamate in the orbitofrontal cortex during REM sleep, which could be related to the increased activity in paralimbic structures observed in humans using functional neuroimaging, as well as to the proposed role of REM sleep on retention of emotional memories.

Animals↗
PubMed2006

Low frequency electrical stimulation through subdural electrodes in a case of refractory status epilepticus.

OBJECTIVE: We delivered low frequency stimulation through subdural electrodes to suppress seizures in a case of refractory status epilepticus (RSE). METHODS: A 26-year-old female developed RSE after several days of febrile illness. Seizure control required continuous infusion of two anesthetics plus high doses of 2-4 enteral antiepileptic drugs. After 3 months of RSE, subdural strips were placed to determine surgical candidacy. Five independent ictal onset zones were identified. Because she was a poor candidate for epilepsy surgery and had a poor prognosis, the implanted subdural electrodes were used to administer 0.5 Hz stimulations to the ictal onset zones in 30 min trains daily for 7 consecutive days in an attempt to suppress seizures. RESULTS: After 1 day of stimulation, one anesthetic agent was successfully discontinued. Seizures only returned by the 4th day when the second anesthetic had been reduced by 60%. Upon returning, seizures arose from only one of the 5 original ictal onset zones. Unfortunately, RSE persisted, and she eventually died. CONCLUSIONS: In this case of RSE, low frequency stimulation through subdural electrodes transiently suppressed seizures from all but one ictal onset zone and allowed significant reduction in seizure medication. SIGNIFICANCE: Low frequency cortical stimulation may be useful in suppressing seizures.

Action Potentials↗
PubMed2006

Extracellular adenosine in the human brain during sleep and sleep deprivation: an in vivo microdialysis study.

STUDY OBJECTIVES: To examine the pattern of extracellular adenosine in the human brain during sleep deprivation, sleep, and normal wake. DESIGN: Following recovery from implantation of clinical depth electrodes, epilepsy patients remained awake for 40 continuous hours, followed by a recovery sleep episode. SETTING: Neurology ward at UCLA Medical Center. PATIENTS OR PARTICIPANTS: Seven male epilepsy patients undergoing depth electrode localization of pharmacologically refractory seizures. INTERVENTIONS: All subjects were implanted with depth electrodes, a subset of which were customized to contain microdialysis probes. Microdialysis samples were collected during normal sleep, sleep deprivation, and recovery sleep from human amygdalae (n = 8), hippocampus (n = 1), and cortex (n = 1). MEASUREMENTS AND RESULTS: In none of the probes did we observe an increase in extracellular adenosine during the sleep deprivation. There was a significant, though very small, diurnal oscillation (2.5%) in 5 of the 8 amygdalae. There was no effect of epileptogenicity on the pattern of extracellular adenosine. CONCLUSIONS: Our observations, along with those in animal studies, indicate that the role of extracellular adenosine in regulating sleep pressure is not a global brain phenomenon but is likely limited to specific basal forebrain areas. Thus, if energy homeostasis is a function of sleep, an increased rate of adenosine release into the extracellular milieu of the amygdala, cortex, or hippocampus is unlikely to be a marker of such a process.

Adenosine↗
PubMed2005

A lack of effect from transcranial magnetic stimulation (TMS) on the vagus nerve stimulator (VNS).

OBJECTIVE: The effects of transcranial magnetic stimulation (TMS) on vagus nerve stimulation (VNS) are unknown. Understanding these effects is important before exposing individuals with an implanted VNS to TMS, as could occur in epilepsy or depression TMS research. To explore this issue, the TMS-induced current in VNS leads and whether TMS has an effect on the VNS pulse generator was assessed. METHODS: Ex vivo measurement of current in VNS leads during single-pulse TMS and pulse generator function before, during, and after single-pulse TMS was assessed. RESULTS: At the highest intensity and with the TMS coil held approximately 5 mm from the VNS wires, a 200 nA, 1.0 ms current was induced by TMS. This translates to an induced charge density of 3.3 nC/cm2/phase. The function of the pulse generator was unaffected by single-pulse TMS, even when its case was directly stimulated by the coil. CONCLUSIONS: TMS-induced current in VNS electrodes was not only well outside of the range known to be injurious to peripheral nerve, but also below the activation threshold of nerve fibers. SIGNIFICANCE: Using single-pulse TMS in individuals with VNS should not result in nerve stimulation or damage. Furthermore, single-pulse TMS does not affect the VNS pulse generator's function.

Brain↗
PubMed2005

Characterization of an S-locus receptor protein kinase-like gene from peach.

A receptor-like protein kinase gene (Ppsrkl1) was isolated from a peach (Prunus persica (L.) Batsch.) bark cDNA library prepared with RNAs isolated from bark collected in December (cold acclimated). Sequence analysis indicated that this gene is related to the S-locus family of receptor protein kinases (SRKs) and that it shares greatest homology with ZMPK1 from maize and At4g32300 from Arabidopsis, both of which are intron-less genes. In bark tissues, Ppsrkl1 is induced by water deficit treatment, repressed by short-day photoperiods and showed no response to cold treatment. The Ppsrkl1 mRNA also increased in roots in response to water deficit. In fruit, Ppsrkl1 shows no response up to 6 h after wounding, but at 12 and 24 h after wounding, Ppsrkl1 mRNA shows an abrupt decline. This decline was prevented by the addition of salicylic acid to the wound site. The Ppsrkl1 mRNA rapidly decreased in fruit after 10-min exposure to UV-C radiation, followed by a return to normal levels within 1.5 h. Taken together, these experiments indicate that Ppsrkl1 is negatively regulated by light and positively influenced by salicylic acid treatment in fruit and water stress in bark and roots.

Acclimatization↗
PubMed2005

Analysis of chronic seizure onsets after intrahippocampal kainic acid injection in freely moving rats.

PURPOSE: The goal of this study was to analyze the transition period between interictal and ictal activity in freely moving rats with recurrent spontaneous seizures after unilateral intrahippocampal kainic acid (KA) injection. METHODS: Pairs of tungsten electrodes (50 microm O/D) were implanted bilaterally under anesthesia at symmetrical points in the dentate gyrus (DG) and CA1 regions of anterior and posterior hippocampi and entorhinal cortex of adult Wistar rats. Stimulating electrodes were placed in the right angular bundle and KA was injected into the right posterior CA3 area of hippocampus after 1 week of baseline EEG recording. Beginning 24 h after injection, electrographic activity was recorded with video monitoring for seizures every day for 8 h/day for 60 days. RESULTS: Seventy percent of seizures started locally in the DG ipsilateral to injection, with an increase in frequency of interictal EEG spikes (hypersynchronous type, HYP), and 26% of seizures started with a decrease of EEG amplitude with parallel increase in frequency (low-voltage fast type, LVF). During HYP seizures, a significant increase was observed in amplitude of beta-gamma range frequencies, ripple frequency, and fast ripple (FR) frequency, whereas during LVF seizure, an increase was noted only in the beta-gamma range. In all cases but one, an EEG wave preceded ripple and FR oscillations. Before seizure onset, the amplitude of DG-evoked responses to single pulses decreased, whereas the amplitude of the response to the second pulse delivered at 30-ms interval increased. CONCLUSIONS: If ripple and FR oscillations indicate the seizure-generating neuronal substrate, these areas must be small and widespread, so that the probability of recording from them directly is very low. The decreased response to electrical stimulation before seizures could indicate a protective inhibitory mechanism that contains or prevents seizure occurrence. The presence of decreased paired-pulse suppression could indicate a network predisposition to follow an external input with a certain frequency.

Animals↗
PubMed2005

Analysis of seizure onset on the basis of wideband EEG recordings.

Seventy-five seizure onsets recorded with depth electrodes in the frequency band from 0.1 to 70 Hz were analyzed in 19 patients with intractable temporal lobe epilepsy. It was shown that 89% of low-voltage fast-type seizures contained an initial slow wave, whereas hypersynchronous-type seizures did not show an initial slow wave. Voltage depth profile analysis illustrated that the peak amplitude of the initial slow-wave onset was in white matter, whereas the peak amplitude of hypersynchronous onset was in deep temporal areas (hippocampus, entorhinal cortex, or amygdala). The difference in voltage depth profiles suggests that these two types of seizure onsets have different mechanisms of generation. The absence of phase reversal of the initial slow wave in white matter or at the border of deep temporal areas indicates a possible nonneuronal mechanism of generation.

Amygdala↗
PubMed2004

Large-scale microarray gene expression analysis in discrete electrophysiologically identified neuronal clusters.

The normal processes of learning and memory as well as the pathological progress of various neurological diseases may result in changes in gene expression in small, local populations of neurons in any given brain area, leading to the occurrence of specific patterns of electrical activity without easily detectable changes in the morphology of this brain area. One way of identifying these changes might be the comparison of gene expression of areas which generate and areas which do not generate specific patterns of electrical activity. A method for microbiopsy of limited (0.5-1.0 mm3) tissue samples from electrophysiologically identified areas of neurons generating epileptiform activity in the rat brain is described. Here we demonstrate that total RNA isolated from individual microbiopsy samples might be successfully used for microarray based gene expression analysis of any discretely localized neuronal group which can be identified electrophysiologically, including neurons in cortical columns, cell assemblies or other functional units.

Animals↗
PubMed2004

High-frequency oscillations recorded in human medial temporal lobe during sleep.

The presence of fast ripple oscillations (FRs, 200-500 Hz) has been confirmed in rodent epilepsy models but has not been observed in nonepileptic rodents, suggesting that FRs are associated with epileptogenesis. Although studies in human epileptic patients have reported that both FRs and ripples (80-200 Hz) chiefly occur during non-rapid eye movement sleep (NREM), and that ripple oscillations in human hippocampus resemble those found in nonprimate slow wave sleep, quantitative studies of these oscillations previously have not been conducted during polysomnographically defined sleep and waking states. Spontaneous FRs and ripples were detected using automated computer techniques in patients with medial temporal lobe epilepsy during sleep and waking, and results showed that the incidence of ripples, which are thought to represent normal activity in animal and human hippocampus, was similar between epileptogenic and nonepileptogenic temporal lobe, whereas rates of FR occurrence were significantly associated with epileptogenic areas. The generation of both FRs and ripples showed the highest rates of occurrence during NREM sleep. During REM sleep, ripple rates were lowest, whereas FR rates remained elevated and were equivalent to rates observed during waking. The predominance of FRs within the epileptogenic zone not only during NREM sleep, but also during epileptiform-suppressing desynchronized episodes of waking and REM sleep supports the view that FRs are the product of pathological neuronal hypersynchronization associated with seizure-generating areas.

Animals↗
PubMed2004

High-frequency oscillations after status epilepticus: epileptogenesis and seizure genesis.

PURPOSE: To investigate the temporal relation between high-frequency oscillations (HFOs) in the dentate gyrus and recurrent spontaneous seizures after intrahippocampal kainite-induced status epilepticus. METHODS: Recording microelectrodes were implanted bilaterally in different regions of hippocampus and entorhinal cortex. A guide cannula for microinjection of kainic acid (KA) was implanted above the right posterior CA3 area of hippocampus. After recording baseline electrical activity, KA (0.4 microg/0.2 microl) was injected. Beginning on the next day, electrographic activity was recorded with video monitoring for seizures every day for 8 h/day for > or = 30 days. RESULTS: Of the 26 rats studied, 19 revealed the appearance of sharp-wave activity and HFOs in the frequency range of 80 to 500 Hz in the dentate gyrus ipsilateral to the KA injection. In the remaining seven rats, no appreciable activity was noted in this frequency range. In some rats with recurrent seizures, HFOs were in the ripple frequency range (100-200 Hz); in others, HFOs were in the fast ripple frequency range (200-500 Hz), or a mixture of both oscillation frequencies was found. The time of detection of the first HFOs after status epilepticus varied between 1 and 30 days, with a mean of 6.3 +/- 2.0 (SEM). Of the 19 rats in which HFO activity appeared, all later developed recurrent spontaneous seizures, whereas none of the rats without HFOs developed seizures. The sooner HFO activity was detected after status epilepticus, the sooner the first spontaneous seizure occurred. A significant inverse relation was found between the time to the first HFO detection and the subsequent rate of spontaneous seizures. CONCLUSIONS: A strong correlation was found between a decreased time to detection of HFOs and an increased rate of spontaneous seizures, as well as with a decrease in the duration of the latent period between KA injection and the detection of spontaneous seizures. Two types of HFOs were found after KA injection, one in the frequency range of 100 to 200 Hz, and the other, in the frequency range of 200 to 500 Hz, and both should be considered pathological, suggesting that both are epileptogenic.

Animals↗
PubMed2004

Electrical stimulation of the posteromedial thalamus modulates breathing in unanesthetized fetal sheep.

Having previously shown that lesions in the posteromedial group of thalamic nuclei abolish hypoxic inhibition of fetal breathing, we devised this study to identify thalamic loci that depress breathing by focal stimulation of specific sectors of the caudal thalamus and adjacent structures. Multipolar electrode arrays consisting of a series of eight stimulation contacts at 1.25-mm intervals were implanted vertically through guide cannulae into the caudal diencephalon of 12 chronically catheterized fetal sheep (>0.8 term), and central neural tissue was stimulated between adjacent contacts. Each site was stimulated repeatedly with increasing current searching for spatial and stimulus strength parameters for a reliable alteration in respiratory rate. Respiratory period increased when stimulation involved areas of the parafascicular nuclear complex (Pf), which more than doubled the mean period compared with the baseline of 0.90 +/- 0.19 s. The change in respiratory period was due to an increase in expiratory time, whereas inspiratory time and breath amplitude were not significantly affected. Breathing period and expiratory time were also increased when the stimulations involved the intralaminar wing surrounding the mediodorsal nucleus, the rostral central gray, zona incerta, and ventral tegmental area. Reductions in respiratory frequency occurred less consistently, with stimulation involving surrounding zones including the sub-Pf, ventromedial nucleus, and ventrobasal nuclear complex. These findings support the hypothesis that a restricted area of the posteromedial thalamus (principally Pf) constitutes part of a neuronal circuitry that modulates respiratory motoneurons.

Animals↗
PubMed2003

Spatial stability over time of brain areas generating fast ripples in the epileptic rat.

PURPOSE: Fast ripples (FRs) are interictal, pathological, high-frequency oscillations in the 200- to 600-Hz range, which can be recorded from limbic regions capable of generating spontaneous seizures in rodent models of epilepsy and in human mesial temporal lobe epilepsy. To evaluate the spatial stability of FR-generating brain areas over long periods, we monitored interictal FR oscillations in rats with chronic recurrent spontaneous seizures. METHODS: After unilateral intrahippocampal injection of kainic acid, 22 rats were video monitored until spontaneous behavioral seizures occurred, and then implanted with multiple hippocampal, dentate gyrus, and entorhinal cortex microelectrodes. Electrophysiological monitoring of microelectrode sites was carried out during daily 8-h recordings for periods ranging from 6 to 98 days. RESULTS: Interictal FRs were recorded from discretely localized areas, adjacent to non-FR-generating areas in dentate gyrus and entorhinal cortex. The location of interictal FR oscillations remained fixed, and the electrophysiological pattern of FRs remained the same over the time of our study. For the duration of monitoring, sites initially recording interictal FRs continued to display FR oscillations, and sites that initially did not record FRs never demonstrated FR activity. A direct relation was seen between the total number of electrode contacts recording interictal FRs and the frequency of spontaneous seizure generation (p < 0.0001). CONCLUSIONS: These results suggest that interictal FRs reflect abnormal discharges from a fixed pathologic substrate imbedded within less-epileptogenic tissue, and that spontaneous seizure frequency is dependent on the extent and distribution of this pathologic substrate.

Animals↗
PubMed2002

Sleep states differentiate single neuron activity recorded from human epileptic hippocampus, entorhinal cortex, and subiculum.

Animal models of epilepsy have shown that synchronous burst firing is associated with epileptogenesis, yet the evidence from human studies linking neuronal synchrony and burst firing to epileptogenesis remains equivocal. Sleep-wake states have been shown to differentially modulate the generation of epileptiform EEG spikes between brain regions of greater and lesser seizure-generating potential, providing information that helps to identify the primary epileptogenic region. Using these state-dependent mechanisms to assist us in identifying neuronal correlates of human epilepsy, we recorded interictal neuronal activity from mesial temporal lobe (MTL) areas in epileptic patients implanted with depth electrodes required for medical diagnosis during polysomnographically defined sleep-wake states. Results show that single neurons recorded ipsilateral to seizure-initiating MTL ("epileptic") areas had significantly higher firing rates (p = 0.01) and burst propensity (p = 0.01) and greater synchrony of discharges (p = 0.003) compared with neurons recorded from contralateral non-seizure-generating MTL ("non-epileptic") areas. In particular, during episodes of slow wave sleep (SWS) and rapid eye movement (REM) sleep, epileptic hippocampal neurons had significantly higher burst rates compared with non-epileptic hippocampal neurons (both p = 0.01). In contrast, during episodes of wakefulness (Aw), no difference in burst firing between epileptic and non-epileptic hippocampal neurons was observed. Furthermore, synchronous firing was significantly higher between epileptic MTL neurons compared with non-epileptic MTL neurons during SWS (p = 0.04) and REM sleep (p = 0.02), but no difference in neuronal synchrony was found between epileptic and non-epileptic neurons during Aw. These results provide evidence that sleep states differentially modulate abnormal epileptogenic neuronal discharge properties within human MTL and confirm that neuronal burst firing and enhanced neuronal synchrony observed in experimental animal models of epilepsy characterizes human epilepsy as well.

Action Potentials↗
PubMed2002

Increased afterdischarge threshold during kindling in epileptic rats.

The effects of daily electrical kindling stimulation of the perforant pathway were investigated in an excitotoxic rat model of epilepsy with chronic seizures in order to learn whether the preexisting epileptic condition would facilitate or retard kindling. Sprague-Dawley rats with recurrent spontaneous seizures 4-8 months after unilateral intrahippocampal kainic acid (KA) injection were implanted with recording electrodes in the hippocampus and stimulating electrodes in the perforant path. Daily stimulation for 10 s at 5 Hz was given for 15 days. The afterdischarge (AD) threshold and the AD duration of kindled KA rats were compared before and during kindling with those of a kindled control group. In the control group, as expected, mean AD thresholds decreased ( P<0.01), while AD duration progressively increased. Although AD threshold was the same in KA and control groups at the start of kindling, in the KA group a significant increase in threshold occurred from the beginning to the end of kindling ( P<0.01). Behaviorally, KA rats showed stage 4 or 5 seizures on the first stimulation, and stage 3-5 seizures during the remainder of kindling. Paired pulse testing showed facilitation of late components of the dentate gyrus field potential at the beginning of kindling, and suppression of late components at the end, in the KA rats. A significant decrease in the rate of spontaneous seizures in KA rats was noted during the period of kindling ( P=0.04). These results suggest that electrical stimulation of the perforant path may strengthen homeostatic seizure suppressing mechanisms, and may provide insights into novel approaches to the treatment of clinical seizures in temporal lobe epilepsy.

Animals↗
PubMed2002

Local generation of fast ripples in epileptic brain.

Aperiodic high-frequency oscillations (>100 Hz) reflect a short-term synchronization of neuronal electrical activity. It has been shown in the epileptic brain that spontaneous oscillations in the frequency range of 250-600 Hz reflect action potential population bursts of synchronously discharging neuronal clusters. These oscillations occur in the early stages of epileptogenesis in areas adjacent to the brain lesion and may trigger the formation of seizure-generating neuronal networks. We studied the extent of the area generating oscillations in the frequency range of 250-600 Hz [fast ripples (FRs)] in intrahippocampal kainic acid-treated rats with spontaneous seizures, by analyzing voltage versus depth profiles of FRs in hippocampal and parahippocampal areas in freely moving animals and by spatial mapping in hippocampal slice preparations in vitro. The strength of inhibition was compared in areas with and without FRs using a paired-pulse paradigm. The extent of the areas generating FRs did not exceed 1 mm(3). The areas generating FRs became broader after the application of the GABA(A) receptor antagonist bicuculline. Paired-pulse fast inhibition at 15-30 msec intervals was similar in areas generating FRs and areas not generating FRs. Our data illustrate that hypothesized clusters of highly interconnected neurons are capable of overcoming interneuron feedback inhibition, resulting in generation of epileptiform bursts, eventually leading to seizure activity.

Action Potentials↗