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Biomedical subjects

I Feinberg

Publications and source records attributed to I Feinberg.

At least 19 recordsLinked to original sources
PubMed2006

Homeostatic behavior of fast Fourier transform power in very low frequency non-rapid eye movement human electroencephalogram.

Basic research shows that the physiological and molecular mechanisms of very low frequency (<1 Hz) electroencephalogram (EEG) waves of non-rapid eye movement (NREM) sleep differ from those of the higher (1-4 Hz) delta frequencies. Human studies show that the across-NREM period dynamics of very low frequency and 1-4 Hz EEG also differ. These differences and the reported failure of very low frequency EEG power to increase after a night of total sleep deprivation raise the question of whether very low frequency EEG shows the other homeostatic properties established for higher delta frequencies. Here we tested the relation of very low frequency EEG power density to prior waking duration across a normal day and whether these low frequencies meet another criterion for homeostatic sleep EEG: conservation of power across a late nap and post-nap sleep. Data from 19 young adults recorded in four separate sessions of baseline, daytime nap and post-nap sleep were analyzed. Power density in very low frequency NREM EEG increased linearly when naps were taken later in the day (i.e. were preceded by longer waking durations). In the night following an 18:00 h nap, very low frequency power was reduced by roughly the amount of power in the nap. Thus, very low frequency EEG meets two major homeostatic criteria. We hypothesize that these low frequencies reflect the executive rather than the functional processes by which NREM sleep reverses the effects of waking brain activity.

Adult↗
PubMed2004

The metabotropic glutamate (mGLU)2/3 receptor antagonist LY341495 [2S-2-amino-2-(1S,2S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-yl)propanoic acid] stimulates waking and fast electroencephalogram power and blocks the effects of the mGLU2/3 receptor agonist ly379268 [(-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate] in rats.

The highly selective metabotropic glutamate (mGlu)2/3 receptor agonist LY379268 [(-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate] completely suppresses rapid eye movement (REM) sleep and strongly depresses theta (6-10 Hz) and high-frequency (10-60 Hz) power in the waking and nonrapid eye movement (NREM) EEG, effects consistent with depressed brain excitation (arousal). We hypothesized the selective mGlu2/3 receptor antagonist LY341495 [2S-2-amino-2-(1S,2S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-yl)propanoic acid] given alone would 1) increase arousal, producing sleep-wake EEG effects opposite those of LY379268, and 2) block/reverse the effects of LY379268 when the drugs are coadministered. Rats with implanted electrodes were injected with 1, 5, or 10 mg/kg LY341495 at hour 5.5 of the dark period. In the coadministration study the rats received the same dose of LY341495 followed 30 min later by 1 mg/kg LY379268. LY341495 alone increased waking by reducing NREM and REM sleep. LY341495 also depressed low-frequency and stimulated high-frequency EEG power. It produced a sharp spike in theta power in waking but not NREM sleep, a striking state-dependent difference in pharmacological response. These changes indicate that blocking mGlu2/3 receptors increases brain arousal. Moreover, they show that mGlu2/3 receptors actively support arousal even in the absence of heightened glutamate excitation. The coadministration experiment demonstrates that LY341495 is selective in vivo since it dose-dependently attenuates or reverses the sleep-wake EEG effects of the highly selective mGlu2/3 receptor agonist LY379268. The capacity of mGlu2/3 receptor agonists and antagonists to alter the sleep wake balance suggests they could be developed to enhance sleep or sustain arousal. Their opposing actions on theta EEG could test the putative role of these oscillations in memory consolidation.

Amino Acids↗
PubMed2002

The selective group mGlu2/3 receptor agonist LY379268 suppresses REM sleep and fast EEG in the rat.

Studies of ionotropic receptors indicate that glutamate (Glu) neurotransmission plays a role in sleep. Here, we show for the first time that metabotropic 2/3 Glu (mGlu2/3) receptors play an active or permissive role in the control of REM sleep. The potent, selective, and systemically active mGlu2/3 receptor agonist LY379268 was administered systemically in doses of 1.0 and 0.25 mg/kg sc. The drug produced a dose-dependent suppression of rapid eye movement (REM) sleep and fast (10-50 Hz) EEG in non-rapid eye movement (NREM) sleep. The 1.0-mg/kg effect on REM sleep was remarkably powerful: REM sleep was totally suppressed in the 6-h postinjection and reduced by 80% in the next 6 h. NREM duration was unchanged during the REM suppression in spite of the strong and unusual depression of EEG power in fast NREM frequencies. These sleep and EEG effects were unaccompanied by motor or behavioral abnormalities. We hypothesize that the REM and the fast EEG suppression were both caused by a depression of brain arousal levels by LY379268. If correct, depressing arousal by reducing excitatory neurotransmission with an mGlu2/3 receptor agonist produces electrophysiological effects that differ drastically from those produced by depressing arousal by enhancing neural inhibition with GABAergic drugs. This different approach to modifying the excitation/inhibition balance in the brain might yield novel therapeutic actions.

Amino Acids↗
PubMed2001

Internight reliability and benchmark values for computer analyses of non-rapid eye movement (NREM) and REM EEG in normal young adult and elderly subjects.

OBJECTIVE: To determine the reliability of computer measured non-rapid eye movement (NREM) and REM frequency bands in the 0.3-45 Hz range and to provide benchmark data for these measures in young normal (YN) and elderly normal (EN) subjects (Ss). METHODS: Sleep EEG was recorded in 19 YN and 19 EN Ss on 4 non-consecutive baseline nights and simultaneously quantified as fast Fourier transform (FFT) power and 3 zero-cross period-amplitude (PA) measures: integrated amplitude, time in band and average wave amplitude. RESULTS: The shapes of both the FFT and PA spectra differed among Ss but were highly consistent within individuals. Inter-night reliability of the separate frequency bands was correspondingly high. Despite substantial age effects, the reliability of computer-measured sleep EEG in the elderly equaled that of the YN Ss. Within both the YN and EN groups, the shapes of the NREM and REM spectral curves differed significantly. The NREM and REM also differed significantly in the two age groups. CONCLUSIONS: Computer-measured sleep EEG is highly reliable across non-consecutive nights in both young and elderly normal Ss. The trait-like stability of these measures suggests they are genetically determined. This possibility is supported by twin study data that show strong heritability for FFT-measured waking EEG. The different shapes of NREM and REM spectra add further evidence that these are fundamentally different states of brain organization. The age differences in spectral shape, along with PA data for wave incidence, demonstrate that age effects on sleep EEG are not caused by changes in skull impedance or other non-cerebral factors.

Adult↗
PubMed2001

A simple method for computer quantification of stage REM eye movement potentials.

We describe a simple method for computer quantification of eye movement (EM) potentials during REM sleep. This method can be applied by investigators using either period-amplitude (PA) or Fast Fourier Transform (FFT) spectral EEG analysis without special hardware or computer programming. It provides good correlations with visual ratings of EM in baseline sleep and after administration of GABAergic hypnotics. We present baseline data for both PA and FFT measures for 16 normal subjects, studied for 5 consecutive nights. Both visually rated and computer-measured EM density (EMD) showed high night-to-night correlations across baseline and drug nights and the computer measures detected the EMD suppression that is produced by GABAergic drugs. Measurement of EM in addition to stage REM provides biologically significant information and application of this simple computer method, which does not require pattern recognition algorithms or special hardware, could provide reliable data that can be compared across laboratories.

Computers↗
PubMed2000

High internight reliability of computer-measured NREM delta, sigma, and beta: biological implications.

BACKGROUND: Computer analysis of the sleep electroencephalogram (EEG) waveforms is widely employed, but there have been no systematic studies of its reliability. METHODS: The most commonly used computer methods are power spectral analysis with the fast-Fourier transform (FFT) and period amplitude analysis (PAA) with zero cross or zero first derivative half-wave measurement. We applied all three computer methods to the digitized EEG of 16 normal subjects who underwent 5 consecutive nights of baseline (placebo) recording. We evaluated the internight reliability of three non-rapid eye movement (NREM) frequency bands of special importance to sleep research: delta (0.3-3 Hz), sigma (12-15 Hz), and beta (15-23 Hz). RESULTS: Both FFT and the two methods of PAA gave excellent internight reliability for delta and sigma. Even a single night of recording correlated highly (r >.9) with the 5-night mean. Beta reliability was lower but still highly significant for both the PAA and the FFT measures. CONCLUSIONS: Computer-analyzed sleep EEG data are highly reliable. Period amplitude methods demonstrate that wave incidence and period as well as amplitude are reliable, indicating that the reliability of composite measures (FFT power, PAA integrated amplitude) is not solely based on individual differences in EEG amplitude. The high internight stability of NREM delta indicates that it possesses traitlike characteristics and is relatively independent of day-to-day variations in state.

Adult↗
PubMed2000

Depression and sleep disorders: clinical relevance, economic burden and pharmacological treatment.

A wide range of studies have been published over the past two decades that involve the intersection of sleep EEG, insomnia, psychiatric illness (especially depressive disorders) and psychopharmacology. Much of value has been discovered, but there have also been false starts and contradictory results. There is in fact strong evidence that insomnia is associated with medical and psychiatric illness and that the sleepiness associated with insomnia is the cause of many accidents. Thus, the direct (visits to doctors, cost of sleeping medication, complications from use of these medications) and indirect (accidents, quality of life) costs of insomnia are enormous and constitute a major public health problem in the industrialized countries. Believing that it is now timely to assess the state of this important research area, a consensus conference was convened on June 26-28, 1998, in Porto Cervo (Italy) to attempt to clarify the important issues and findings on the clinical effect of the different classes of antidepressant drugs on sleep quality in depression. The participants' consensus on some of the main topics is presented with the hope that this discussion and analysis will contribute to productive research in this important field.

Antidepressive Agents↗
PubMed1999

A comparison of period amplitude analysis and FFT power spectral analysis of all-night human sleep EEG.

Zero-cross and zero-derivative period amplitude analysis (PAA) data were compared with power spectral analysis (PSA) data obtained with the fast Fourier transform in all-night sleep EEG from 10 subjects. Although PAA zero-cross-integrated amplitude showed good agreement with PSA power in 0.3-2 Hz, zero-cross analysis appears relatively ineffective in measuring 2-4 Hz and above waves. However, PAA zero-derivative measures of peak-trough amplitude correlated well with PSA power in 2-4 Hz. Thus, while PAA appears able to measure the entire EEG spectrum, the analytic technique should be changed from zero cross to zero derivative at about 2 Hz in human sleep EEG. PAA and PSA both demonstrate robust and interrelated across-night oscillations in three frequency bands: delta (0.3-4 Hz); sigma (12-16 Hz); and fast beta (20-10 Hz). The frequencies between delta and sigma, and between sigma and fast beta, did not show clear across-night oscillations using either method, and the two methods showed lower epoch-to-epoch agreement in these intermediate bands. The causes of this reduced agreement are not immediately clear, nor is it obvious which method gives more valid results. We believe that the three strongly oscillating frequency bands represent fundamental properties of the human sleep EEG that provide important clues to underlying physiological mechanisms. These mechanisms are more likely to be understood if their dynamic properties are preserved and measured naturalistically rather than being forced into arbitrary sleep stages or procrustean models. Both PAA and PSA can be employed for such naturalistic studies. PSA has the advantages of applying the same analytic method across the EEG spectrum and rests on more fully developed theory. Combined zero-cross and zero-derivative PAA demonstrates EEG oscillations that closely parallel those observed with spectral power, and the PAA measures do not rely on assumptions about the spectral composition of the signal. In addition, both PAA techniques can measure the relative contributions of wave amplitude and incidence to total power: These waveform characteristics represent different biological processes and respond differentially to a wide range of experimental conditions.

Adult↗
PubMed1999

Comparison of MK-801 and sleep deprivation effects on NREM, REM, and waking spectra in the rat.

In previous studies, we showed that blockade of the cation channel gated by NMDA glutamate receptors with ketamine or MK-801 massively stimulates NREM delta. We now test whether this NREM delta stimulation is physiological by comparing the EEG response following MK-801 to the EEG response following sleep deprivation (SD). Our previous studies measured only NREM 1-4 Hz EEG with period-amplitude analysis (PAA). Here we extended the analysis of MK-801 effects on sleep EEG by applying power spectral analysis (PSA) to examine delta and higher frequency spectra (.2-100 Hz) in NREM and by including REM and waking spectra. The changes in EEG spectra following MK-801 and SD were remarkably similar. Both SD and MK-801 produced their largest changes in NREM delta and REM 10-20 Hz power. There were some differences in the high frequency EEG, but the overall similarity of the PSA spectra in all three vigilance states after MK-801 and SD supports the possibility that MK-801 stimulated physiologic sleep, perhaps by increasing the need for homeostatic recovery from the metabolic effects of NMDA channel blockade.

Animals↗
PubMed1999

Schizophrenia--a disorder of the corollary discharge systems that integrate the motor systems of thought with the sensory systems of consciousness.

BACKGROUND: In spite of intensive research, no causal anatomical lesion has been found in schizophrenia. It may instead be caused by malfunctioning circuits in the corollary discharge, feed forward (CD-FF) systems of thought. AIMS: To integrate with the CD-FF hypothesis recent data showing that subcortical motor systems participate in thinking. METHODS: We review CD-FF concepts in relation to recent evidence that 'motor' brain structures participate in cognitive processing. RESULTS: Malfunctioning of CD-FF systems that integrate thinking and consciousness could produce auditory hallucinations, delusions and disorganised thought. CONCLUSIONS: We hypothesise that the pathophysiology of schizophrenia lies in integrative circuits of basal ganglia, thalamus and frontal cortex. Fruitful research directions would include elucidation of CD-FF circuits at even higher brain levels, the behaviour of these circuits during dreaming, and their responses to late maturational events including synaptic elimination.

Cognition Disorders↗
PubMed1998

Haloperidol potentiates the EEG slowing of MK-801 despite blocking its motor effects: implications for the PCP model of schizophrenia.

Haloperidol (HP) can block both the motor stimulation and the neurotoxic vacuolization of MK-801, suggesting that the two drugs have antagonistic brain actions. However, we show here that the modest EEG slowing produced by HP and MK-801 individually is massively potentiated when the drugs are combined. This finding challenges the argument for the PCP model of schizophrenia that assumes a general antagonism of neuroleptics and NMDA channel blockers. It further suggests that blockade of MK-801 motor effects is an inadequate test for antipsychotic drug actions. Our data indicate that intact function of D2 receptors (or other HP targets) is required to prevent generalized EEG slowing in the presence of NMDA channel blockade, a possibility of potential clinical interest.

Animals↗
PubMed1998

Overall survival of the medical oncologist: a new outcome measurement in cancer medicine.

BACKGROUND: Changing patterns of patient referral, decreasing payments for service provision, confusing network participation and reimbursement, as well as challenges to autonomous clinical decision-making jeopardize the traditional role of the oncologist in delivering cancer care. The cancer patient also may be at risk with unproven cancer delivery systems that displace the oncologist as decision-maker and care provider. The authors have constructed a model that preserves the oncologist's clinical and financial autonomy while meeting marketplace demands for improved access, decreasing costs and preserved quality of care. METHODS: During a 4-year period, a group of private practice medical oncologists initiated a formal business plan to evaluate marketplace needs, then designed and implemented a novel cancer care delivery model. The model required reconfiguring the practice into an integrated Joint Commission on Accreditation of Healthcare Organizations-certified cancer service corporation, providing medical, radiation, and gynecologic oncology. Palliative care, pain management, psychologic, and nutritional services were instituted as well as the vertical integration of home health and hospice care. Clinical pathways and treatment protocols were designed to enhance patient care and facilitate cost-of-care projections in designated populations using a cancer incidence forecasting model. Outcomes analysis are performed as part of ongoing continuous quality improvement, which continues to change this health care delivery system. RESULTS: In the 3 years since implementation of the model, the practice has increased from 16 to 24 physicians, and the number of offices has increased from 12 to 17. Patient encounters, both new and established, have doubled. Cost of services, specifically hospitalization, have been reduced by 50%. Clinical research referrals have increased 300%. Physician compensation has improved >20%. CONCLUSIONS: The model created a low cost, high value provider not burdened by allocated overhead. Decentralized care enhanced community access, which improved patient compliance, enhanced patient satisfaction, decreased hospitalization, and thereby decreased cost. The horizontal structure permited the flexibility for varied purchaser products and politically sensitive physician and hospital provider panels. Consensus-based protocol and pathway determination achieved maximum physician participation, which preserved clinical and financial autonomy, decreased variance, and facilitated clinical research.

Age Distribution↗
PubMed1997

Coadministered pentobarbital anesthesia postpones but does not block the motor and sleep EEG responses to MK-801.

In previous studies with Sprague-Dawley rats, we demonstrated that NMDA channel blockade during waking massively stimulates the delta (1-4 Hz) EEG of non-rapid eye movement (NREM) sleep. However, non-competitive channel blockers also produce neurotoxicity that is manifested by posterior cingulate vacuolization and heat shock protein production. These neurotoxic effects can be blocked by coadministering gabaergic drugs, including barbiturates and benzodiazepines, with the MK-801. To determine whether delta stimulation by MK-801 would be similarly blocked, we administered an anesthetic dose (40 mg/kg) of pentobarbital followed immediately by 0.3 mg/kg of MK-801. Neither the MK-801 motor syndrome nor the NREM delta stimulation was blocked. When the rats recovered from nearly two hours of barbiturate anesthesia, they behaved as though they had just received the MK-801 injection, exhibiting the typical motor syndrome, spikes in the waking EEG and strong stimulation of NREM delta EEG. These findings support our previous evidence that NREM delta stimulation by NMDA channel blockade does not depend on toxic brain changes. They also raise interesting questions regarding the fate of MK-801 during pentobarbital anesthesia. We propose that the drug is not metabolized during the period of anesthesia because it is sequestered within the NMDA cation channel. However, neurons do not respond to the channel block because they have been rendered inert by the anesthesia. When the neurons emerge from anesthesia, the cascade of MK-801 events unfolds. This and other possible explanations can be tested experimentally. Establishing the fate of MK-801 during barbiturate anesthesia could shed new light on the cellular processing of non-competitive NMDA channel blockers.

Animals↗