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PubMed1999

Increased episodic release and disorderliness of prolactin secretion in both micro- and macroprolactinomas.

To quantify prolactin (PRL) secretion patterns, ten untreated (female) microprolactinoma patients and six (male) macroprolactinoma patients underwent repetitive blood sampling every 10 min over 24 h. PRL release activity was analyzed from plasma PRL concentration (immunofluorimetric assay) profiles via a model-independent discrete peak detection program (Cluster) and a waveform-independent deconvolution technique (Pulse). Diurnal variations were analyzed by cosinor analysis. The number of distinct PRL pulses (mean +/- S.E.M.) was increased in patients: microprolactinoma 18.6 +/- 0.6/24 h versus female controls 12.4 +/- 0.6 (P = 6.7 x 10-s), and macroprolactinoma 18.0 +/- 0.9 versus male controls 13.5 +/- 0.8/24 h (P = 0.003). In patients, PRL pulse height, amplitude, pulse area and interpeak nadir concentrations were each greatly elevated compared with gender-matched controls. By 2-component deconvolution analysis, the mean nadir PRL secretion rate in microprolactinoma patients was augmented 20-fold at 0.408 +/- 0.089 microgram/l per min versus in female controls 0.019 +/- 0.009 microgram/l per min (P < 0.001); and in macroprolactinoma by 130-fold at 2.067 +/- 0.693 micrograms/l per min versus male controls 0.016 +/- 0.001 microgram/l per min (P = 0.001). Corresponding 24 h mean PRL secretion rates were in women, 0.658 +/- 0.147 and 0.044 +/- 0.018 (P < 0.001), and in men, 3.309 +/- 1.156 and 0.035 +/- 0.010 micrograms/l per min (P = 0.001), being respectively 15- and 94-fold increased in tumors. The estimated PRL production per day was 160 +/- 15 and 187 +/- 20 micrograms in male and female controls respectively. PRL production was 2860 +/- 640 micrograms in female patients with microadenomas (P < 0.001), and 37,800 +/- 5900 micrograms in male macroadenoma patients (P = 0.001). Cosinor analysis of the plasma concentrations revealed a significant rhythm in nine of ten, patients with a microadenoma, and in five of six with a macroadenoma. The same method applied to pulse height and amplitude disclosed a significant rhythm for PRL pulse height, but not for pulse amplitude, suggesting preserved rhythmicity of baseline interpulse nadir PRL concentrations. Approximate entropy (ApEn), a scale- and model-independent regularity statistic, averaged 1.6559 +/- 0.028 in microprolactinoma patients versus 0.8128 +/- 0.079 in female controls (P = 1.7 x 10(-8)); ApEn in macroadenomas was 1.5674 +/- 0.054 versus male controls 0.8773 +/- 0.076 (P = 1.7 x 10(-5), signifying greater secretory irregularity in the patients. Compared with microadenomas, macroadenomas exhibited a higher mean plasma concentration, overall mean PRL secretion rate, nadir secretion rate and pulse area, but similar peak frequency. We conclude that PRL secretion by prolactinomas is characterized by increased plasma PRL episodicity of release, increased total (15- to 100-fold) and basal (20- to 130-fold) secretion rates, and increased disorderlines of minute-to-minute secretion. These abnormalities of secretory control are very similar to those for GH and ACTH identified earlier in acromegaly and Cushing's disease respectively, thus suggesting mechanistic generality of pituitary tumor secretory derangements, independent of the particular hormone.

Adult↗

PubMed2001

Short-term estradiol replacement in postmenopausal women selectively mutes somatostatin's dose-dependent inhibition of fasting growth hormone secretion.

How estradiol stimulates pulsatile GH secretion in the human is not well understood. Here, we test the clinical hypothesis that estradiol stimulates GH secretion, in part, by opposing somatostatin's inhibition of GH release. To this end, 13 estrogen-withdrawn postmenopausal women received placebo or 1 mg micronized estradiol-17beta orally, twice daily for 14 days, in a prospectively randomized, patient-blinded, within-subject cross-over design. For each intervention, the dose-dependent suppressive actions of somatostatin were evaluated by infusing 0 (saline), 3, 10, 30, 100, or 300 microg/1.73 m(2).h somatostatin-14 continuously, iv, for 3 h, on separate mornings, in the fasting state, 48 h apart. Blood was sampled at 10-min intervals for 2 h before, for 3 h concurrently with, and for 1 h after each infusion. Serum GH concentrations were quantitated in an ultrasensitive chemiluminescence-based assay (detection threshold, 0.005 microg/L). In the estrogen-deficient milieu, constant iv somatostatin infusions inhibited steady-state serum GH concentrations (valley mean during the last 60 min of the infusion interval) in a dose-dependent manner (P < 10(-4) interventional effect). Maximally effective doses of somatostatin reduced the latter by 89 +/- 6.1% (mean +/- SEM) below the subject-specific preinfusion baseline. Estrogen administration increased the serum estradiol concentration from 12 +/- 1 to 245 +/- 35 pg/mL [42 +/- 4 to 920 +/- 110 pmol/L] (P < 10(-4)); decreased serum concentrations of LH (P = 0.018), FSH (P < 10(-4)), and insulin-like growth factor-I (P = 0.003); and elevated the fasting (6-h mean) serum GH concentration from 0.41 +/- 0.07 to 0.87 +/- 0.27 (P = 0.011). Estradiol supplementation did not alter somatostatin's maximal suppression of GH by 89 +/- 4.7% (P < 10(-4) below subject-specific preinfusion baseline), thus signifying unchanging somatostatin efficacy. In contrast, estradiol replacement significantly elevated the half-maximally inhibitory dose of infused somatostatin by 13.5-fold, from 0.43 (0.38-0.48, 95% group statistical confidence intervals) (placebo) to 6.0 (5.2-7.0) (estradiol) microg/1.73 m(2)/h (P < 10(-4)), denoting muting of somatostatin's inhibitory potency. The latter inference was confirmed by a concomitant 4-fold decrease in the exponential steepness of the somatostatin inhibitory dose-response function; viz., mean 1.42 (1.49 to 1.33) (placebo) vs. 0.34 (0.62 to 0.26) (estradiol) slope units (P < 10(-4)). The foregoing effects were specific, because estrogen did not alter somatostatin's dose-dependent enhancement (P < 10(-4)) of the orderliness of GH release patterns, as quantitated via the approximate entropy regularity statistic. In summary, short-term replacement of estradiol to midfollicular phase levels in postmenopausal women selectively reduces the potency, but not the efficacy, of somatostatin's dose-dependent inhibition of GH release. Estrogen supplementation does not modify somatostatin's reciprocal enhancement of the quantifiable orderliness (approximate entropy) of the GH secretory process. Accordingly, we postulate that estradiol can facilitate pulsatile GH secretion, in part, by opposing the repressive actions of somatostatin.

Cross-Over Studies↗

PubMed2000

Freeze-drying of polycaprolactone and poly(D,L-lactic-glycolic) nanoparticles induce minor particle size changes affecting the oral pharmacokinetics of loaded drugs.

The present study was geared at identifying the conditions to stabilize poly (D,L-lactic-glycolic) (PLGA) and polycaprolactone (PCL) nanoparticles (NP) by freeze-drying with several cryoprotective agents. Differential scanning calorimetry and freeze-thawing studies were used to optimize the lyophilization process. These studies showed that all samples were totally frozen at -45 degrees C and evidenced the necessity of adding sucrose, glucose, trehalose or gelatine to preserve the properties of NP regardless of the freezing procedure. However, only 20% sucrose and 20% glucose exerted an acceptable lyoprotective effect on PLGA and PCL NP, respectively. Nonetheless, the final to initial size ratios ( approximately 1.5) indicated that particle size was slightly affected in both cases. In vivo studies with CyA-loaded PCL NP whose sizes matched those obtained after NP preparation (100 nm) and after being lyophilized (160 nm) showed that the changes of particle size might have some relevance on drug pharmacokinetics. The MRT was significantly (P<0.05) modified after an oral CyA dose of 5 mg/kg and the treatment with 160-nm sized CyA-loaded NP produced a higher drug partition into the liver of Wistar rats potentially affecting the toxic and immunosuppressive profile of the drug. Therefore, although the particle size changes induced by NP lyophilization were slight, they need to be carefully evaluated and cannot be neglected.

Administration, Oral↗

PubMed2003

Heart rate variability and recurrence of atrial fibrillation after electrical cardioversion.

BACKGROUND: Heart rate (HR) variability has been shown to predict spontaneous onset of atrial fibrillation (AF). This study was designed to test the hypothesis that HR variability after electrical cardioversion (CV) of persistent AF predicts the recurrence of AF. METHODS: Various time and frequency domain measures of HR variability, along with the non-linear measures of HR dynamics, were analyzed from the 24-hour ECG recordings in 78 patients with persistent AF after restoration of sinus rhythm with electrical CV. RESULTS: During the follow-up of one month, 27 patients (35%) had recurrence of AF. The patients with AF recurrence had significantly higher standard deviation of all R-R intervals (SDNN 117 +/- 34 versus 100 +/- 29 P < 0.05), increased high-frequency (InHF 5.7 +/- 0.6 versus 5.3 +/- 0.7 P < 0.05 ), low-frequency (InLF 6.2 +/- 0.8 versus 5.6 +/- 0.9 P < 0.01) and very-low-frequency (InVLF 7.1 +/- 0.8 versus 6.5 +/- 0.8 P < 0.01) power spectral components of HR variability than those who remained in sinus rhythm. Approximate entropy, a measure of complexity of HR dynamics, and the short-term fractal scaling exponent did not differ between the groups, but the long-term power-law slope beta was steeper among the patients who remained in sinus rhythm (P < 0.05). During the first week after the CV, increased HF power (highest tertile) was the most powerful predictor of AF recurrence with odds ratio of 2.8 (95% confidence interval 1.0 to 8.0, P < 0.05). Increased VLF power spectral component at baseline predicted best the late recurrence of AF with odds ratio of 3.3 (95% confidence interval 1.6 to 7.2, P < 0.01). No clinical or echocardiographic variable predicted the recurrence of AF. CONCLUSIONS: Increased HR variability in all major power spectral bands is associated with late recurrence of AF after electrical CV. Enhanced cardiac vagal outflow, reflected as an increased HF power spectral component, seems to predict specifically the early recurrence of AF after the CV.

Aged↗

PubMed2003

Acipimox enhances spontaneous growth hormone secretion in obese women.

We hypothesized that a high circulating free fatty acid (FFA) concentration is involved in the pathogenesis of hyposomatotropism associated with obesity. To evaluate this hypothesis, 10 healthy premenopausal women (body mass index 33.8 +/- 1.0 kg/m(2)) were studied in the follicular phase of their menstrual cycle at two occasions with a time interval of at least 8 wk, where body weight remained stable. Subjects were randomly assigned to treatment with either acipimox (an inhibitor of lipolysis, 250 mg orally 4 times daily) or placebo in a double-blind crossover design, starting 1 day before admission until the end of the blood sampling period. Blood samples were taken during 24 h with a sampling interval of 10 min for assessment of growth hormone (GH) concentrations, and GH secretion was estimated by deconvolution analysis. Identical methodology was used to study GH secretion in a historical control group of age-matched normal weight women. GH secretion was clearly blunted in obese women (total daily release 66 +/- 10 vs. lean controls: 201 +/- 23 mU x l(Vd)(-1) x 24 h(-1), P = 0.005, where l(Vd) is lite of distribution volume). Acipimox considerably enhanced total (113 +/- 50 vs. 66 +/- 10 mU x l(Vd)(-1) x 24 h(-1), P = 0.02) and pulsatile GH secretion (109 +/- 49 vs. 62 +/- 30 mU x l(Vd)(-1) x 24 h(-1), P = 0.02), but GH output remained lower compared with lean controls. Further analysis did not show any relationship between the effects of acipimox on GH secretion and regional body fat distribution. In conclusion, acipimox unleashes spontaneous GH secretion in obese women. It specifically enhances GH secretory burst mass. This might mean that lowering of systemic FFA concentrations by acipimox modulates neuroendocrine mechanisms that orchestrate the activity of the somatotropic ensemble.

Adipose Tissue↗

PubMed2006

Stratus not altocumulus: a new view of the yeast protein interaction network.

Systems biology approaches can reveal intermediary levels of organization between genotype and phenotype that often underlie biological phenomena such as polygenic effects and protein dispensability. An important conceptualization is the module, which is loosely defined as a cohort of proteins that perform a dedicated cellular task. Based on a computational analysis of limited interaction datasets in the budding yeast Saccharomyces cerevisiae, it has been suggested that the global protein interaction network is segregated such that highly connected proteins, called hubs, tend not to link to each other. Moreover, it has been suggested that hubs fall into two distinct classes: "party" hubs are co-expressed and co-localized with their partners, whereas "date" hubs interact with incoherently expressed and diversely localized partners, and thereby cohere disparate parts of the global network. This structure may be compared with altocumulus clouds, i.e., cotton ball-like structures sparsely connected by thin wisps. However, this organization might reflect a small and/or biased sample set of interactions. In a multi-validated high-confidence (HC) interaction network, assembled from all extant S. cerevisiae interaction data, including recently available proteome-wide interaction data and a large set of reliable literature-derived interactions, we find that hub-hub interactions are not suppressed. In fact, the number of interactions a hub has with other hubs is a good predictor of whether a hub protein is essential or not. We find that date hubs are neither required for network tolerance to node deletion, nor do date hubs have distinct biological attributes compared to other hubs. Date and party hubs do not, for example, evolve at different rates. Our analysis suggests that the organization of global protein interaction network is highly interconnected and hence interdependent, more like the continuous dense aggregations of stratus clouds than the segregated configuration of altocumulus clouds. If the network is configured in a stratus format, cross-talk between proteins is potentially a major source of noise. In turn, control of the activity of the most highly connected proteins may be vital. Indeed, we find that a fluctuation in steady-state levels of the most connected proteins is minimized.

Computational Biology↗

PubMed2006

Solar cycles and their relationship to human disease and adaptability.

In this paper, we show that 11-year solar cycle peaks predispose humans to disease, but also endow creativity and adaptability. We give several examples of diseases that are modulated by light and present evidence for an effect of intensity and variation in sunlight, primarily ultraviolet radiation (UVR), on the human genome. The birth dates of nearly 237,000 unique clients in the Maine Medicaid database collected from 1995 to 2004, inclusive, were related to solar cycle irradiance for the past seventy-one years, encompassing seven solar cycles. The sample was divided into four general categories of disease: mental/behavioral illnesses; metabolic diseases; autoimmune diseases; neoplasms. The birth months for those clients born in any given year were arranged in the form of a winter/summer ratio in order to more clearly appreciate the seasonality inherent in each disease category. Solar cycles were separated into chaotic (approximately three times as irradiant) or non-chaotic according to the Gutenberg-Richter power law and the uncertainty inherent in predicting solar storms. The results show that radiation peaks in solar cycles and particularly in chaotic solar cycles (CSCs) are associated with a higher incidence of mental disorders, suggesting the sensitivity of ectodermal embryonic tissues to UVR. Autoimmune diseases have intermediate sensitivity, while the neoplasms in the study, primarily of endoderm, appear suppressed by peak UVR intensity. The ratio of the number of clients born in CSC cycles to non-CSC cycles was highest for the more genetic mental diseases, like schizophrenia and bipolar disorder, but as that ratio decreased, the clients with diseases like multiple sclerosis and rheumatoid arthritis showed more environmental features manifested as a greater winter/summer birth month ratio that was significantly different than that of the average client in the whole data set. The paper presents evidence that latitude, e.g., variation in light, is an added stress to the immune system (especially at 53-54 degrees N. latitude) that is involved in nearly all human disease. We hypothesize that introns, the presumptive engenderers of gene control, modulate the effects of UVR, particularly for the neoplasms studied. We conclude that intermittent and largely unpredictable peak solar cycle radiation has been the fundamental engine of evolution, forcing organisms to adapt to mutagenic UVR and producing enough damage to instigate genetic variation. Probably a chance genetic mutation over 80,000 years ago produced a human brain capable of abstract thought and consciousness. The slight genetic instability that favored an adaptable, creative brain also produced other somatic variations that present phenotypically as disease, but largely expressed after natural selection (reproduction) and associated with the inexorable entropy of aging.

Adaptation, Physiological↗

PubMed2006

Conformational sampling with implicit solvent models: application to the PHF6 peptide in tau protein.

Implicit solvent models approximate the effects of solvent through a potential of mean force and therefore make solvated simulations computationally efficient. Yet despite their computational efficiency, the inherent approximations made by implicit solvent models can sometimes lead to inaccurate results. To test the accuracy of a number of popular implicit solvent models, we determined whether implicit solvent simulations can reproduce the set of potential energy minima obtained from explicit solvent simulations. For these studies, we focus on a six-residue amino-acid sequence, referred to as the paired helical filament 6 (PHF6), which may play an important role in the formation of intracellular aggregates in patients with Alzheimer's disease. Several implicit solvent models form the basis of this work--two based on the generalized Born formalism, and one based on a Gaussian solvent-exclusion model. All three implicit solvent models generate minima that are in good agreement with minima obtained from simulations with explicit solvent. Moreover, free-energy profiles generated with each implicit solvent model agree with free-energy profiles obtained with explicit solvent. For the Gaussian solvent-exclusion model, we demonstrate that a straightforward ranking of the relative stability of each minimum suggests that the most stable structure is extended, a result in excellent agreement with the free-energy profiles. Overall, our data demonstrate that for some peptides like PHF6, implicit solvent can accurately reproduce the set of local energy minimum arising from quenched dynamics simulations with explicit solvent. More importantly, all solvent models predict that PHF6 forms extended beta-structures in solution, a finding consistent with the notion that PHF6 initiates neurofibrillary tangle formation in patients with Alzheimer's disease.

Alzheimer Disease↗

PubMed2003

The effects of spontaneous activity, background noise, and the stimulus ensemble on information transfer in neurons.

Information theory is playing an increasingly important role in the analysis of neural data as it can precisely quantify the reliability of stimulus-response functions. Estimating the mutual information between a neural spike train and a time varying stimulus is, however, not trivial in practice and requires assumptions about the specific computations being performed by the neuron under study. Consequently, estimates of the mutual information depend on these assumptions and their validity must be ascertained in the particular physiological context in which experiments are carried out. Here we compare results obtained using different information measures that make different assumptions about the neural code (i.e. the way information is being encoded and decoded) and the stimulus ensemble (i.e. the set of stimuli that the animal can encounter in nature). Our comparisons are carried out in the context of spontaneously active neurons. However, some of our results are also applicable to neurons that are not spontaneously active. We first show conditions under which a single stimulus provides a good sample of the entire stimulus ensemble. Furthermore, we use a recently introduced information measure that is based on the spontaneous activity of the neuron rather than on the stimulus ensemble. This measure is compared to the Shannon information and it is shown that the two differ only by a constant. This constant is shown to represent the information that the neuron's spontaneous activity transmits about the fact that no stimulus is present in the animal's environment. As a consequence, the mutual information measure based on spontaneous activity is easily applied to stimuli that mimic those seen in nature, as it does not require a priori knowledge of the stimulus ensemble. Finally, we consider the effect of noise in the animal's environment on information transmission about sensory stimuli. Our results show that, as expected, such 'background' noise will increase the trial-to-trial variability of the neural response to repeated presentations of a stimulus. However, the same background noise can also increase the variability of the spike train and hence can lead to increased information transfer in the presence of background noise. Our study emphasizes how different assumptions can lead to different predictions for the information transmission of a neuron. Assumptions about the computations being performed by the system under study as well as the stimulus ensemble and background noise should therefore be carefully considered when applying information theory.

Action Potentials↗

PubMed2004

Realistic protein-protein association rates from a simple diffusional model neglecting long-range interactions, free energy barriers, and landscape ruggedness.

We develop a simple but rigorous model of protein-protein association kinetics based on diffusional association on free energy landscapes obtained by sampling configurations within and surrounding the native complex binding funnels. Guided by results obtained on exactly solvable model problems, we transform the problem of diffusion in a potential into free diffusion in the presence of an absorbing zone spanning the entrance to the binding funnel. The free diffusion problem is solved using a recently derived analytic expression for the rate of association of asymmetrically oriented molecules. Despite the required high steric specificity and the absence of long-range attractive interactions, the computed rates are typically on the order of 10(4)-10(6) M(-1) sec(-1), several orders of magnitude higher than rates obtained using a purely probabilistic model in which the association rate for free diffusion of uniformly reactive molecules is multiplied by the probability of a correct alignment of the two partners in a random collision. As the association rates of many protein-protein complexes are also in the 10(5)-10(6) M(-1) sec(-1) range, our results suggest that free energy barriers arising from desolvation and/or side-chain freezing during complex formation or increased ruggedness within the binding funnel, which are completely neglected in our simple diffusional model, do not contribute significantly to the dynamics of protein-protein association. The transparent physical interpretation of our approach that computes association rates directly from the size and geometry of protein-protein binding funnels makes it a useful complement to Brownian dynamics simulations.

Computer Simulation↗

PubMed1998

Hypothalamo-pituitary disconnection of the late-gestation ovine fetus results in profound changes in cortisol secretion that are not reflected in commensurate changes in adrenocorticotropin secretion.

A prepartum increase in fetal glucocorticoid concentrations is essential for the perinatal transition to extrauterine life for many mammalian species. In the case of the sheep, this increase in cortisol is also the trigger for parturition, and depends upon an intact hypothalamo-pituitary unit. Fetal sheep that have undergone hypothalamo-pituitary disconnection (HPD) fail to have a prepartum cortisol surge or initiate labor, despite apparently normal fetal ACTH concentrations in late gestation. We have investigated whether a defect exists in the regulation of pulsatile neurohormone secretion in the pituitaryadrenal axis of the HPD sheep fetus, by comparing immunoreactive (ir) ACTH and cortisol secretory dynamics in intact and HPD fetuses at 126 and 145 days of gestation (normal gestation length, 147 days). The fetal surgery was conducted at 115 days of gestation. Blood samples were collected at 5-min intervals for 2 h on each experimental day, and the resulting irACTH and cortisol concentrations were analyzed by multiple-parameter deconvolution and cross-correlation analysis. Basal irACTH secretion was less (P < 0.01) in HPD fetuses than intact fetuses at 126 days, but it had recovered by 145 days. There were no differences in irACTH half-life or the number or duration of irACTH secretory bursts between the two groups of fetuses or the two gestational ages (GAs). The size of the irACTH secretory bursts was not affected by the operation, but it increased with GA to a similar extent in both groups of fetuses (P < 0.01). In keeping with the observations for irACTH secretion, there was no effect of age or the operation on cortisol half-life or on the number or duration of cortisol secretory bursts. In contrast, there were dramatic age-related increases (P < 0.01) in the basal cortisol secretion rate and the size of the cortisol secretory bursts in the intact, but not the HPD, fetuses. Cross-correlation analysis revealed a significant (P < 0.01) concordance between irACTH and cortisol secretion in only the intact fetuses at 126 days; this was not apparent in the intact fetuses at 145 days, or in the young or old HPD fetuses. These findings confirm a major defect in cortisol secretion in the late-gestation HPD fetus but suggest that this is not caused by defects in irACTH secretion. Together with other observations, these data suggest that ACTH may not be the sole, or primary, regulator of adrenal cortisol secretion in the late-gestation ovine fetus.

Adrenocorticotropic Hormone↗

PubMed2004

Origin, structure, and role of background EEG activity. Part 1. Analytic amplitude.

OBJECTIVE: To explain the neural mechanisms of spontaneous EEG by measuring the spatiotemporal patterns of synchrony among beta-gamma oscillations during perception. METHODS: EEGs were measured from 8 x 8 (5.6 x 5.6 mm2) arrays fixed on the surfaces of primary sensory areas in rabbits that were trained to discriminate visual, auditory or tactile conditioned stimuli (CSs) eliciting conditioned responses (CRs). EEG preprocessing was by (i) bandpass filtering to extract the beta-gamma range (deleting theta-alpha); (ii) low-pass spatial filtering (not high-pass Laplacians used for localization), (iii) spatial averaging (not time averaging used for evoked potentials), and (iv) close spacing of 64 electrodes for simultaneous recording in each area (not sampling single signals from several areas); (v) novel algorithms were devised to measure synchrony and spatial pattern stability by calculating variances among patterns in 64-space derived from the 8 x 8 arrays (not by fitting equivalent dipoles). These methodological differences are crucial for the proposed new perspective on EEG. RESULTS: Spatial patterns of beta-gamma EEG emerged following sudden jumps in cortical activity called 'state transitions'. Each transition began with an abrupt phase re-setting to a new value on every channel, followed sequentially by re-synchronization, spatial pattern stabilization, and a dramatic increase in pattern amplitude. State transitions recurred at varying intervals in the theta range. A novel parameter was devised to estimate the perceptual information in the beta-gamma EEG, which disclosed 2-4 patterns with high information content in the CS-CR interval on each trial; each began with a state transition and lasted approximately 0.1 s. CONCLUSIONS: The function of each primary sensory neocortex was discontinuous; discrete spatial patterns occurred in frames like those in cinema. The frames before and after the CS-CR interval had low content. SIGNIFICANCE: Derivation and interpretation of unit data in studies of perception might benefit from using multichannel EEG recordings to define distinctive epochs that are demarcated by state transitions of neocortical dynamics in the CS-CR intervals, particularly in consideration of the possibility that EEG may reveal recurring episodes of exchange and sharing of perceptual information among multiple sensory cortices. Simultaneously recorded, multichannel beta-gamma EEG might assist in the interpretation of images derived by fMRI, since high beta-gamma EEG amplitudes imply high rates of energy utilization. The spatial pattern intermittency provides a tag to distinguish gamma bursts from contaminating EMG activity in scalp recording in order to establish beta-gamma recording as a standard clinical tool. Finally, EEG cannot fail to have a major impact on brain theory.

Acoustic Stimulation↗