Biomedical subjects

Anthony G Hudetz

Publications and source records attributed to Anthony G Hudetz.

13 recordsLinked to original sources

PubMed2006

Digit tapping model of functional activation in the rat somatosensory cortex.

To establish a non-invasive model for functional activation of the rat somatosensory cortex, the forepaw digits of halothane-anesthetized rats were tapped while the blood flow (laser-Doppler flow, LDF) and somatosensory evoked potential (SSEP) responses in the forelimb area of the somatosensory cortex (S1FL) were measured. The distal phalanges of the forepaw digits were lightly tapped for 10s with an aluminum bar at frequencies between 1 and 40 Hz, with 0.4 cm total bar displacement. The LDF signal was normalized to the baseline preceding each stimulus block and averaged. The LDF response to digit tapping in the contralateral, but not ipsilateral S1FL, commenced within 1s, peaked at 11+/-0.5% (S.E.M.) above baseline within 2-3s, decreased to a plateau of 5+/-0.3% for the duration of the stimulation, and returned to baseline within 5-10s following tapping cessation. The LDF peak and plateau were not significantly different at different tapping frequencies. In the contralateral, but not ipsilateral, S1FLs, tapping produced an SSEP with positive (P1) and negative (N1) peaks at 27+/-0.5 and 47+/-0.2m s, respectively, after onset of the tap stimulation. As the tapping frequency increased from 1 to 20 Hz, the P1-N1 peak-to-peak amplitude decreased. At 30 and 40 Hz, the shortened interstimulus interval entrained the individual SSEPs into a steady-state evoked response. This study demonstrates that a robust functional activation of the forelimb region of primary somatosensory cortex of halothane-anesthetized rats can be produced by non-invasively tapping the forepaw digits and quantified with LDF and SSEP.

Analysis of Variance↗

PubMed2006

Isoflurane disrupts anterio-posterior phase synchronization of flash-induced field potentials in the rat.

Consciousness presumes a set of integrated functions such as sensory processing, attention, and interpretation, and may depend upon both local and long-range phase synchronization of neuronal activity in cerebral cortex. Here we investigated whether volatile anesthetic isoflurane at concentrations that produce loss of consciousness (LOC) disrupts long-range anterio-posterior and local anterior synchronization of neuronal activity in the rat. In six rats, deep electrodes were chronically implanted in the primary visual cortex (V1) and in two areas of the motor cortex (M1 and M2) for recording of intracortical event-related potentials (ERP). Thirty discrete flashes were presented at random interstimulus intervals of 15-45 s, and ERPs were recorded at stepwise increasing isoflurane concentrations of 0-1.1%. Neuronal synchronization was estimated using wavelet coherence computed from the ERP data band-pass filtered at 5-50 Hz. We found that (1) in the waking state, long-range anterio-posterior coherence in 5-25 Hz and 25-50 Hz frequency bands was significantly higher than local anterior coherence; (2) anterio-posterior coherence in both 5-25 Hz and 26-50 Hz bands was significantly reduced by isoflurane in a concentration-dependent manner; (3) local anterior coherence was not affected by isoflurane at any of the concentrations studied. These findings suggest that a disruption of long-range anterio-posterior rather than local anterior synchronization of neuronal activity precedes the anesthetic-induced loss of consciousness.

Anesthetics, Inhalation↗

PubMed2005

Volatile anesthetics disrupt frontal-posterior recurrent information transfer at gamma frequencies in rat.

We seek to understand neural correlates of anesthetic-induced unconsciousness. We hypothesize that cortical integration of sensory information may underlie conscious perception and may be disrupted by anesthetics. A critical role in frontal-posterior interactions has been proposed, and gamma (20-60 Hz) oscillations have also been assigned an essential role in consciousness. Here we investigated whether general anesthetics may interfere with the exchange of information encoded in gamma oscillations between frontal and posterior cortices. Bipolar electrodes for recording of event-related potentials (ERP) were chronically implanted in the primary visual cortex, parietal association and frontal association cortices of six rats. Sixty light flashes were presented every 5s, and ERPs were recorded at increasing concentrations of halothane or isoflurane (0-2%). Information exchange was estimated by transfer entropy, a novel measure of directional information transfer. Transfer entropy was calculated from 1-s wavelet-transformed ERPs. We found that (1) feedforward transfer entropy (FF-TE) and feedback transfer entropy (FB-TE) were balanced in conscious-sedated state; (2) anesthetics at concentrations producing unconsciousness augmented both FF-TE and FB-TE at 30 Hz but reduced them at 50 Hz; (3) reduction at 50 Hz was more pronounced for FB-TE, especially between frontal and posterior regions; (4) at high concentrations, both FF-TE and FB-TE at all frequencies were at or below conscious-sedated baseline. Our findings suggest that inhalational anesthetics preferentially impair frontal-posterior FB information transfer at high gamma frequencies consistent with the postulated role of frontal-posterior interactions in consciousness.

Anesthetics, Inhalation↗

PubMed2005

Functional hyperemic response in the rat visual cortex under halothane anesthesia.

To establish a model for functional hyperemia in the rat visual cortex, cortical blood flow responses to flash stimulation were measured with the laser Doppler flow (LDF) technique at various levels of halothane anesthesia. The concentration-dependent effect of halothane on arterial pressure and its consequent effect on the hyperemic response were also investigated. Using a stroboscopic light source, 10 flashes at 1 min intervals were delivered to the left eye of 12 Sprague-Dawley rats. LDF responses were measured bilaterally in the monocular primary visual cortex (V1M) at steady state halothane concentrations between 0.4 and 1.4%. In six rats, methoxamine (MX) was infused to prevent halothane-induced hypotension; the remaining rats did not receive MX. In all rats, LDF response to flash commenced within 1s and peaked at 2.5s in the contralateral V1M, but not in ipsilateral V1M. The maximum LDF response was 25% at 0.5% halothane and 12% at 1.4% halothane. In rats without MX infusion, mean arterial pressure (MAP) fell from 138 to 90 mmHg when halothane increased from 0.4 to 1.4%. MX infusion prevented the hypotension, but did not influence the LDF response, suggesting that the halothane's effect was direct rather than pressure-mediated. We demonstrate for the first time, a robust functional hyperemic response to discrete flash stimuli in the primary visual cortex of halothane-anesthetized albino rats that can be measured with LDF over a wide range of halothane concentrations and is not fully suppressed at surgical levels of halothane anesthesia.

Anesthetics, Inhalation↗

PubMed2005

Volatile anesthetics enhance flash-induced gamma oscillations in rat visual cortex.

BACKGROUND: The authors sought to understand neural correlates of anesthetic-induced unconsciousness. Cortical gamma oscillations have been associated with neural processes supporting conscious perception, but the effect of general anesthesia on these oscillations is controversial. In this study, the authors examined three volatile anesthetics, halothane, isoflurane, and desflurane, and compared their effects on flash-induced gamma oscillations in terms of equivalent concentrations producing the loss of righting reflex (1 minimum alveolar concentration for the loss of righting [MAC(LR)]). METHODS: Light flashes were presented every 5 s for 5 min, and event-related potentials were recorded from primary visual cortex of 15 rats with a chronically implanted bipolar electrode at increasing anesthetic concentrations (0-2.4 MAC(LR)). Early cortical response was obtained by averaging poststimulus (0-100 ms) potentials filtered at 20-60 Hz across 60 trials. Late (100-1,000 ms) gamma power was calculated using multitaper power spectral technique. Wavelet decomposition was used to determine spectral and temporal distributions of gamma power. RESULTS: The authors found that (1) halothane, isoflurane, and desflurane enhanced the flash-evoked early cortical response in a concentration-dependent manner; (2) the effective concentration for this enhancement was the lowest for isoflurane, intermediate for halothane, and the highest for desflurane when compared at equal fractions of the concentration that led to a loss of righting; (3) the power of flash-induced late (> 100 ms) gamma oscillations was augmented at intermediate concentrations of all three anesthetic agents; and (4) flash-induced gamma power was not reduced below waking baseline even in deep anesthesia. CONCLUSIONS: These findings suggest that a reduction in flash-induced gamma oscillations in rat visual cortex is not a unitary correlate of anesthetic-induced unconsciousness.

Anesthetics, Inhalation↗

PubMed2004

Effect of relaxation on working memory and the Bispectral Index of the EEG.

Beneficial effects of relaxation on cardiovascular and immune functions and on memory has been implied but an empirical relationship between task performance and anxiety reduction has not been reported. In this study, we investigated whether guided imagery of relatively short duration would decrease S-Anxiety and electroencephalogram Bispectral Index and improve working memory. 42 participants (age: M=39, SD=11, 14 men, 28 women, university students and VA Medical Center employees, recruited by their professor or by fellow employees) underwent relaxation by 16-min. guided imagery or no treatment (control). Spielberger's State-Trait Anxiety Inventory and the WAIS-III Letter-Number Sequencing Test were administered before and after relaxation. S-Anxiety and BIS Index decreased and the Letter-Number test score increased by 30% after relaxation but not in the control group. This score was higher for participants with low anxiety and BIS Index. There was no significant difference between the groups before treatment. The results suggest that guided imagery of short duration produces relaxation as measured by psychological and neurophysiological indices and improves working memory performance.

Adolescent↗

PubMed2003

Cholinergic reversal of isoflurane anesthesia in rats as measured by cross-approximate entropy of the electroencephalogram.

BACKGROUND: Pharmacologic modulation of the state of consciousness is of interest for clinical practice and for a better understanding of anesthetic mechanisms. The cholinergic activating system is an important regulator of the state of consciousness during general anesthesia. Entropy of the electroencephalogram has been proposed as a promising measure of anesthetic depth. The authors have shown that volatile anesthetics decrease cross-approximate entropy (C-ApEn) of the bihemispheric frontal electroencephalogram in rats. The effect of cholinergic agents on C-ApEn has not been examined. Here, the authors test the hypothesis that cholinergic activation reverses the effect of isoflurane anesthesia on C-ApEn. METHODS: An electroencephalogram in the 1- to 100-Hz range was recorded bipolarly, with epidural leads from the frontal cortex of both hemispheres, and used to calculate C-ApEn, which reflects statistical independence of bihemispheric electroencephalographic activity. Cholinesterase inhibitor, neostigmine (25 mug), or the muscarinic agonist oxotremorine (25 mug) were infused intracerebroventricularly while the rats were inhaling 1.0% (0.7 minimum alveolar concentration) isoflurane. In other animals, isoflurane was lowered to 0.4% (0.3 minimum alveolar concentration) to assess the electroencephalogram in a sedated, waking state. RESULTS: At 1.0% isoflurane, C-ApEn decreased by 54% compared with that at 0.4%, but the motor reflex response to tail pinch was still present. Cholinergic agents reversed the electroencephalogram-depressant effect of isoflurane, i.e., C-ApEn rose to the level measured at 0.4% isoflurane. The rise in C-ApEn was paralleled by the appearance of spontaneous limb and orofacial explorative movements, suggesting a return of consciousness. In contrast, cholinergic agents fully blocked the motor reflex to tail pinch. CONCLUSIONS: C-ApEn of the bihemispheric electroencephalogram correlates with the return of spontaneous motor signs but not with the nociceptive reflex. Cerebral cholinergic activation dissociates central and peripheral anesthetic effects. C-ApEn, a novel measure of interhemispheric electroencephalogram independence, is a promising correlate of depth of sedation and state of consciousness.

Algorithms↗

PubMed2002

Effect of volatile anesthetics on interhemispheric EEG cross-approximate entropy in the rat.

Dissimilarity of the electroencephalogram (EEG) between the two hemispheres was characterized by cross-approximate entropy (C-ApEn), an information statistical parameter applicable to nonlinear, aperiodic signals. EEGs were recorded bipolarly with pairs of epidural electrodes in the left and right frontal cortices. The signals were filtered for 1-100 Hz and digitized at 200 Hz. Inhaled anesthetic concentration was varied between 0.3 and 2.1% with 45-min equilibration periods while the rats were breathing spontaneously. Anesthetics produced concentration-dependent changes in C-ApEn. A greater dynamic range of C-ApEn was obtained by reducing the epoch length from 2 s to 100 ms. At a 0.4% inspired agent concentration halothane caused an increase of C-ApEn, whereas isoflurane did not. When the inspired concentrations of both agents were greater than 0.4%, C-ApEn dose-dependently decreased as agent concentrations increased. Isoflurane depressed C-ApEn more than did halothane at all equivalent minimum alveolar concentration levels, but the two agents became equipotent at 1.5% inspired concentration. C-ApEn fell below the awake baseline at 0.8% anesthetic concentration that also abolished the righting reflex. C-ApEn increased after high-pass filtering (>20 Hz) and decreased after-low pass filtering (<20 Hz) of the digitized EEG; the anesthetic dependence of C-ApEn was diminished by both filters. The results suggest that C-ApEn of bihemispheric EEG is a sensitive, agent-specific correlate of anesthetics' central effect.

Anesthetics, Inhalation↗

PubMed2002

Functional cerebral hyperemia is unaffected by isovolemic hemodilution.

BACKGROUND: The cerebral hyperemic effect of hemodilution is well known; however, its mechanism and potential modifying effect on the functional hyperemic response to neuronal activation are unclear. The authors investigated the effects of isovolemic hemodilution on vibrissal stimulation-induced changes in cerebrocortical laser Doppler flow and tissue oxygen tension in the rat. METHODS: The hyperemic response to whisker stimulation was assessed in the whisker barrel cortex of 12 rats anesthetized with chloralose-urethane before and after hemodilution. Graded, isovolemic hemodilution was performed by three repeated withdrawals of 3 ml blood with replacement of equal volume of 5% serum albumin. Measured systemic hematocrit values were 39.3 +/- 1.3% (control), 29.5 +/- 1.0%, 22.3 +/- 1.5%, and 17.0 +/- 1.6% (after the three hemodilution steps). Arterial blood pressure was maintained at control levels with an infusion of methoxamine. Unilateral whisker stimulation was performed with a mechanical actuator at 8 Hz, and 10 cycles of 10 s on-30 s off periods. In six control animals, shed blood was immediately reinfused, resulting in no change in hematocrit, and whisker stimulation was performed using the same timeline as in the other animals. In six additional experiments, resting cerebral cortical oxygen tension was measured using the phosphorescence quenching technique following the same hemodilution protocol. RESULTS: Graded hemodilution increased baseline laser Doppler flow by 5.5 +/- 0.9%, 13 +/- 1.6%, and 23.7 +/- 2.2%. Vibrissal stimulation transiently increased laser Doppler flow by 17.0 +/- 2.0%. The hyperemic response was unchanged after hemodilution and was identical to that seen in the control group in all conditions. Tissue oxygen tension increased slightly but significantly with hemodilution at a rate of 1.4 mmHg per 10% hematocrit change (r = 0.83). Mean arterial pressure, arterial oxygen tension, carbon dioxide tension, and pH were within normal limits in each experimental group and were not different from control during hemodilution. CONCLUSIONS: The results suggest that an increase in baseline flow during hemodilution maintains cortical oxygen supply and consequently preserves the normal functional hyperemic response.

Animals↗

PubMed2002

Isoflurane-induced cerebral hyperemia is partially mediated by nitric oxide and epoxyeicosatrienoic acids in mice in vivo.

BACKGROUND: Despite intense investigation, the mechanism of isoflurane-induced cerebral hyperemia is unclear. The current study was designed to determine the contributions of neuronal nitric oxide synthase, prostaglandins, and epoxyeicosatrienoic acids to isoflurane-induced cerebral hyperemia. METHODS: Regional cerebral cortical blood flow was measured with laser Doppler flowmetry during stepwise increases of isoflurane from 0.0 to 1.2, 1.8, and 2.4 vol% end-tidal concentration in alpha-chloralose-urethane-anesthetized, C57BL/6 mice before and 45 min after administration of the neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI, 40 mg/kg, intraperitoneal), the cyclooxygenase inhibitor indomethacin (INDO, 10 mg/kg, intravenous), and the cytochrome P450 epoxygenase inhibitor N-methylsulfonyl-6-(2-proparglyoxyphenyl)hexanoic acid (PPOH, 20 mg/kg, intravenous). RESULTS: Isoflurane increased regional cerebral cortical blood flow by 9 +/- 3, 46 +/- 21, and 101 +/- 26% (SD) at 1.2, 1.8, and 2.4 vol%, respectively. The increases in regional cerebral cortical blood flow were significantly (*P < 0.05) smaller after 7-NI (5 +/- 6, 29 +/- 19*, 68 +/- 15%*) or PPOH (4 +/- 8, 27 +/- 17*, 67 +/- 30%*), but not after administration of INDO (4 +/- 4, 33 +/- 18 [NS], 107 +/- 35% [NS]). The effect of combined treatment with 7-NI, PPOH, and INDO was not additive and was equal to that of either 7-NI or PPOH alone (5 +/- 5, 30 +/- 12*, 76 +/- 24%*). Chronic treatment of mice for 5 days with 7-NI (2 x 40 mg/kg, intraperitoneal) produced similar decreases in regional cerebral cortical blood flow as those seen with acute administration. Neither PPOH nor INDO conferred a significant additional block of the hyperemia in these animals. CONCLUSIONS: Nitric oxide and epoxyeicosatrienoic acids contribute to isoflurane-induced hyperemia. However, only approximately one third of the cerebral hyperemic response to isoflurane is mediated by autacoids. The remaining part of this response appears to be mediated by a direct action of isoflurane on smooth muscle by some yet-unknown mechanism.

Animals↗

PubMed2002

20-HETE contributes to the acute fall in cerebral blood flow after subarachnoid hemorrhage in the rat.

This study examined the effects of blocking the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) on the acute fall in cerebral blood flow after subarachnoid hemorrhage (SAH) in the rat. In vehicle-treated rats, regional cerebral blood flow (rCBF) measured with laser-Doppler flowmetry fell by 30% 10 min after the injection of 0.3 ml of arterial blood into the cisterna magna, and it remained at this level for 2 h. Pretreatment with inhibitors of the formation of 20-HETE, 17-octadecynoic acid (17-ODYA; 1.5 nmol intrathecally) and N-hydroxy-N'-(4-butyl-2-methylphenyl)formamidine (HET0016; 10 mg/kg iv), reduced the initial fall in rCBF by 40%, and rCBF fully recovered 1 h after induction of SAH. The concentration of 20-HETE in the cerebrospinal fluid rose from 12 +/- 2 to 199 +/- 17 ng/ml after SAH in vehicle-treated rats. 20-HETE levels averaged only 15 +/- 11 and 39 +/- 13 ng/ml in rats pretreated with 17-ODYA or HET0016, respectively. HET0016 selectively inhibited the formation of 20-HETE in rat renal microsomes with an IC(50) of <15 nM and human recombinant CYP4A11, CYP4F2, and CYP4F3 enzymes with an IC(50) of 42, 125, and 100 nM, respectively. These results indicate that 20-HETE contributes to the acute fall in rCBF after SAH in rats.

Amidines↗

PubMed2002

Focal cerebral ischemia in rats produced by intracarotid embolization with viscous silicone.

Many factors contribute to the severity of neuronal cell death and the functional outcome in stroke. We describe an embolic model of focal cerebral ischemia in the rat that does not require craniotomy and is compatible with continuous measurement of regional CBF using multichannel laser Doppler flow (LDF) technique. Either a 22 microliters (large lesion) or 11 microliters (small lesion) bolus of viscous silicone was injected cephalad into the internal carotid artery. Upon injection, LDF decreased abruptly, most severely in the parietal cortex (-74% +/- 5%) in the large lesion and in the occipital cortex (-69% +/- 10%) in the small lesion model. Over the first hour, post-embolization LDF improved in most areas (e.g. -48% +/- 9% parietal, large lesion) but declined in the small lesion group in the occipital region (-81% +/- 8%). CBF measured by [C]14-IAP autoradiography 1 h post-embolization in the large lesion model demonstrated near-hemispheric ischemia (70% of hemisphere) with sparing of cingulate cortex. Autoradiography demonstrated that ischemia in the small lesion was largely cortical. Light microscopy of brains embolized with 11 microliters of dyed silicone showed filling of pial vessels with no silicone in the Circle of Willis or parenchyma. No animals in the large lesion group survived 24 h. Thirteen of 15 animals in the small lesion group survived for two weeks with resolution of initial hemiplegia, ocular asymmetry and weight loss. Hematoxylin-eosin staining two weeks post-embolization showed signs of severe hypoxia and infarction. In conclusion, the intracarotid silicone embolization technique produces a titrable, reproducible permanent ischemic injury by blocking perfusion in the pial circulation, and is amenable to multisite monitoring with laser Doppler flowmetry. The smaller embolus produces cortical infarction with high rate of survival and neurological recovery.

Animals↗

PubMedDate not supplied

Decoupling of the hemodynamic and activation-induced delays in functional magnetic resonance imaging.

PURPOSE: The objective of this study was to develop a technique to decouple the hemodynamic delay from the task-induced delay on a voxel-by-voxel basis in functional magnetic resonance imaging (fMRI) data sets. Prior fMRI studies have reported variability in temporal delays of up to several seconds among activated voxels. It is currently assumed that this variability primarily arises from differences in the onset of task-induced activation, although the precise source of these delays has not been well characterized. Here, we hypothesize that the total delay during task activation can be modeled as a combination of neuronal (caused by differences in onset of neuronal firing), vasomotor (caused by flow changes during activation), and transit (caused by differences in the red blood cell arrival time) delays. METHOD: Subjects were scanned using a sequential dynamic susceptibility contrast (DSC) protocol during rest and fMRI of the motor cortex using a bilateral finger-tapping task. The total delay was determined using correlation coefficient analysis, whereas the intrinsic delay was determined from the DSC MRI. Subtraction of the transit delay from the corresponding total delay for each voxel yielded the task-induced delay. RESULTS: In all subjects, a transit delay of 2.3 (+/-1.1) seconds and a task-induced delay of 0.7 (+/-0.6) second was observed between voxels, which is in good agreement with reports in the literature using other techniques. These results demonstrate the feasibility of the DSC MRI for separating the hemodynamic and task-induced delays in fMRI studies. CONCLUSION: This approach has the potential to elucidate the temporal characteristics of the blood oxygenation level-dependent signal during fMRI as well as to further our understanding of the dynamics of the activation-induced signal in neuroimaging.

Adult↗