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Background: The aim of the present study was to investigate the stress-related changes of a TeamGym competition considering both physiological (i.e. salivary cortisol [sC] and alpha-amylase [sAA]) and psychological (i.e. state anxiety) responses in relation to exercise intensity and competition outcomes., Methods: Eleven (5 males and 6 females) elite TeamGym athletes (age: 21-28 yrs) were administered the State-Trait Anxiety Inventory before an official international TeamGym competition. sAA and sC samples were collected 15 minutes prior to competition, after each apparatus, 10-min and 30-min after competition. Exercise intensity was estimated by heart rate (HR) recording and performance was evaluated by three international judges. All these parameters were correlated with competition outcomes., Results: TeamGym competition posed a low exercise load (most of exercise was performed below 85% of the individual HRmax). Significant increases (P<0.004) in sAA (3.53 fold induction) and state anxiety (P=0.045) were observed, with respect to baseline values. Conversely, sC remained stable throughout the competition. Significant (P=0.029) correlation between sAA, state anxiety and competition outcomes emerged., Conclusions: Present findings provide the first evidence that the psycho-physiological stress response prior to and during competition can affect performance outcome, especially in a technical sport such as TeamGym.

We tested the hypothesis of a relationship between heart rate variability (HRV) and Rolandic mu rhythms in relaxed condition of resting state. Resting state eyes-closed electroencephalographic (EEG) and electrocardiographic (ECG) data were recorded (10-20 System) in 42 healthy adults. EEG rhythms of interest were high-frequency alpha (10.5-13Hz) and low-frequency beta (13-20Hz), which are supposed to form Rolandic mu rhythms. Rolandic and occipital (control) EEG sources were estimated by LORETA software. Results showed a statistically significant (p<0.05, corrected) negative correlation across all subjects between Rolandic cortical sources of low-frequency beta rhythms and the low-frequency band power (LF, 0.04-0.15Hz) of tachogram spectrum as an index of HRV. The lower the amplitude of Rolandic sources of low-frequency beta rhythms (as a putative sign of activity of somatomotor cortex), the higher the LF band power of tachogram spectrum (as a putative sign of sympathetic activity). This effect was specific as there was neither a similar correlation between these EEG rhythms and high-frequency band power of tachogram spectrum (as a putative sign of parasympathetic vagal activity) neither between occipital sources of low-frequency beta rhythms (as a putative sign of activity of visual cortex) and LF band power of tachogram spectrum. These results suggest that Rolandic low-frequency beta rhythms are related to sympathetic activity regulating heart rate, as a dynamic neurophysiologic oscillatory mechanism sub-serving the interaction between brain neural populations involved in somatomotor control and brain neural populations regulating ANS signals to heart for on-going homeostatic adaptations., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the effect of a solo ultraendurance open-water swim on autonomic and nonautonomic control of heart rate (HR)., Methods: A male athlete (age 48 y, height 172 cm, body mass 68 kg, BMI 23 kg/m2) underwent HR-variability (HRV) and circulating catecholamine evaluations at different times before and after an ultraendurance swim crossing the Adriatic Sea from Italy to Albania. HRV was measured in 5-min segments and quantified by time and frequency domain. Circulating catecholamines were estimated by salivary alpha-amylase (sAA) assay., Results: The athlete completed 78.1 km in 23:44 h:min. After arrival, sAA levels had increased by 102.6%. Time- and frequency-domain HRV indexes decreased, as well (mean RR interval, -29,7%; standard deviation of normal mean RR interval, -63,1%; square root of mean squared successive differences between normal-to-normal RR intervals, -49.3%; total power, -74.3%; low frequency, -78.0%; high frequency, -76.4%), while HR increased by 41.8%. At 16-h recovery, sAA had returned to preevent values, while a stable tachycardia was accompanied by reduced HRV measures., Conclusion: To the authors' knowledge, this is the first study reporting cardiac autonomic adjustments to an extreme and challenging ultraendurance open-water swim. The findings confirmed that the autonomic drives depend on exercise efforts. Since HRV changes did not mirror the catecholamine response 16 h postevent, the authors assume that the ultraendurance swim differently influenced cardiac function by both adaptive autonomic and nonautonomic patterns.

Background: The word "stress" describes the status of the body affected by external or internal forces, or "stressors", threatening to alter its dynamic balance or homeostasis. The adaptive changes which occur in reply to stressors are either behavioral or physical. Once a given threshold is surpassed, a systemic reaction takes place involving the "stress system" in the brain together with its peripheral components, the hypothalamic-pituitary-adrenal axis and autonomic sympathetic., Objectives: Stress induces an activation of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. The purpose of this study was to investigate whether the SNS and the HPA axis would show parallel or divergent stress response patterns in a session of first parachute jump., Patients and Methods: Activation of the SNS was evaluated by dosage of salivary alpha-amylase, galvanic skin responses, and heart rate in seven male novice parachutists. Activation of HPA axis was tested by dosage of cortisol. These variables were measured before and 1 minute and 90 minute after the jump., Results: All variables reached a peak at 1 minute post-jump. Salivary alpha-amylase, galvanic skin responses and heart rate did not return to basal value at 90 minutes post-jump, while cortisol returned to basal value at 90 minutes post-jump., Conclusions: This evidence indicates that parachute jumping is accompanied by a dissociation of SNS and HPA response patterns in novice parachutists, showing a slower recovery in sympathetic activity than in cortisol secretion.

Purpose: To evaluate the pacing strategy, rating of perceived exertion (RPE), and mood during a 78.1-km solo ultraendurance open-water swim., Methods: Before and after the event, anthropometric parameters, cortisol, and the profile of mood state (POMS) of 1 male athlete (age 48 y, height 172 cm, body mass 68 kg, body fat 7.2%, athletic achievement: Italian record holder of the Channel Swim) were ascertained. Every 3 h during the event, average swimming speed (SS), stroke rate, stroke length (SL), and RPE were recorded., Results: The athlete completed the event in 23:44 h:min. Compared with the first 3 h of swimming, decreases in SS (-33%) and SL (-25%) were observed between 18 h and 21 h. Thereafter, the athlete increased SS (+41%) and SL (+17%) between 21 h and the end. RPE steadily increased from the beginning to the last 6 h of swimming. Cortisol showed a 23-fold increase. After the event, POMS showed a 500% increase in fatigue, 44% decrease in tension, and 77% decrease in vigor., Conclusion: For the first time ever an athlete crossed the Adriatic Sea. This case study shows that the athlete adopted a variable pacing strategy to complete 78 km. Despite the athlete perceiving his effort at maximum during the last 6 h, the observed increases in SS at the end of the event might substantiate his high potential motivation to accomplish this challenging and unique event.

Aim: The aim of the present study was to investigate heart rate (HR), salivary cortisol (sC) alpha-amylase (sAA) and rating of perceived exertion (RPE) in relation to competition outcome during a half marathon., Methods: HR was monitored and salivary samples were collected during an official half marathon in five Master endurance runners (age 47 ± 7 years). RPE was collected using a 100-mm Visual Analogue Scale (VAS) 30 minutes after the end of competition., Results: Performance corresponded to 94% of their personal best (PB). Athletes spent 53.7% of total race time at intensities above 95% HRmax. RPE showed values of 68 ± 8 mm. With respect to pre-competition values (25.54 ± 6.39 nmol/L), sC concentrations significantly increased (P=0.043) by 59% immediately after the race (40.54 ± 3.95 nmol/L) and remained elevated until 1 h post exercise. Pre-competition sAA concentrations (90.59 ± 42.86 U/mL) were 118% higher (P=0.043) with respect to time-matched baseline values (197.92 ± 132 U/mL). sAA increased (192%; P=0.043) immediately after the race and was higher than time-matched resting samples. The better each athlete performed the greater cortisol increase during exercise (P<0.001). Performance was not correlated to the anticipatory sAA (the percent difference between pre-competition values and time-matched baseline ones) or to the sAA increase during exercise., Conclusion: This is the first attempt to study the stress-related responses during official endurance competitions in master runners. Although the strict criteria of inclusion might have limited the statistical significance, the present findings indicate that endurance competition is a remarkable stressor for psycho-physiological aspects of master athletes.

Aim: The aim of the present study was to investigate the stress--related changes of a TeamGym competition considering both physiological [i.e. salivary cortisol (sC) and alpha--amylase (sAA)] and psychological (i.e. state anxiety) responses in relation to exercise intensity and competition outcomes., Methods: Eleven (5 males and 6 females) elite TeamGym athletes (age: 21--28 yrs) were administered the State--Trait Anxiety Inventory before an official international TeamGym competition. sAA and sC samples were collected 15 minutes prior to competition, after each apparatus, 10--min and 30--min after competition. Exercise intensity was estimated by heart rate (HR) recording and performance was evaluated by three international judges. All these parameters were correlated with competition outcomes., Results: TeamGym competition posed a low exercise load (most of exercise was performed below 85% of the individual HR max ). Significant increases (P<0.004) in sAA (3.53 fold induction) and state anxiety (P=0.045) were observed, with respect to baseline values. Conversely, sC remained stable throughout the competition. Significant (P=0.029) correlation between sAA, state anxiety and competition outcomes emerged., Conclusions: Present findings provide the first evidence that the psycho--physiological stress response prior to and during competition can affect performance outcome, especially in a technical sport such as TeamGym.

Objective: We evaluated the working hypothesis that the EEG activity associated to non-painful and painful stimuli in condition of waking state (no hypnotic procedure) was related to the hypnotizability level., Methods: Hypnotizability level was measured in 16 healthy subjects through the Italian version of the Stanford Hypnotic Susceptibility Scale (SHSS, score: 0-12). EEG data (56 electrodes) were recorded during non-painful and painful electrical stimuli applied to the left index finger. Cortical activity (vertex N1-P2 complex) was compared in subjects with low hypnotizability level (N=8, SHSS:0-6) vs. subjects with high hypnotizability level (N=8, SHSS:7-12)., Results: The amplitude of the N1-P2 complex was lower in the High-hypnotizability compared to the Low-hypnotizability group over primary sensorimotor cortex (C3 and C4 electrodes) and centro-parietal midline areas (Cz and Pz electrodes) for non-painful and painful stimuli. The SHSS showed a statistically significant negative correlation with the vertex N1-P2 complex at C3 and Cz (r=-0.5, p<0.05) electrodes for non-painful stimuli., Conclusion: Compared to the Low-hypnotizability subjects, High-hypnotizability subjects showed a reduced cortical activity related to non-painful and painful stimuli., Significance: The results suggest a relationship between hypnotizability and cortical activity related to non-painful and painful stimuli in the condition of waking state (no hypnotic effect)., (Copyright © 2013. Published by Elsevier Ireland Ltd.)

Objective: Obese subjects without eating disorders were characterised by poor electroencephalographic (EEG) alpha rhythms during resting-state eye-closed condition (Babiloni et al., 2011b). Is this true also for the desynchronisation of alpha rhythms during resting-state eyes opening?, Methods: EEG data were recorded in 15 underweight, 20 normal-weight, and 18 overweight/obese subjects during resting-state eyes-closed and -open conditions. EEG sources were estimated by LORETA for alpha 1 (8-10.5 Hz) and alpha 2 (10.5-13 Hz). The alpha desynchronisation was calculated as the difference eyes-open minus -closed condition., Results: The occipital alpha 1 desynchronisation was lower in overweight/obese and underweight subjects compared with normal-weight subjects (p < 0.000005). The same was true for parietal, occipital and temporal alpha 2 (10.5-13 Hz) desynchronisation (p < 0.000002). The parietal and temporal alpha 1 desynchronisation was lower in overweight/obese than in normal-weight subjects (p < 0.00001). These effects spatially matched those observed in the resting-state eyes-closed condition., Conclusion: Subjects with abnormal weight and normal eating behaviour are characterised by poor alpha desynchronisation during resting-state eyes opening., Significance: Obese subjects without eating disorders show abnormal mechanisms of cortical neural synchronisation and desynchronisation of alpha rhythms in the resting state condition., (Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Here we tested the hypothesis that compared with normal weight non dieting (control) subjects, normal weight successful dieters submitted to a rigorous and continuous monitoring of body weight (i.e. karate athletes) are characterized by an increase of cortical responses to oddball visual stimuli depicting the enlargement of faces or foods, as neural underpinning of attention processes related to the control of weight and eating. Electroencephalographic (EEG) data were recorded in 18 successful dieters (5 females) and 24 non dieting subjects (9 females). The subjects were given frequent (70%) and rare (30%) stimuli depicting faces (FACE), food (FOOD), and landscapes (CONTROL). The task was to click the mouse after the rare stimuli. The rare stimuli depicted the frequent stimuli graphically dilated by 25% along the horizontal axis. Cortical responses accompanying attention processes were probed by the difference between positive event-related potentials peaking around 400-500ms post-stimulus for the rare minus frequent stimuli (P300). The popular freeware LORETA estimated P300 cortical sources. The results showed that in the FACE condition, the amplitude of left frontal (BA 6) and medial parietal (BA 5) P300 sources was higher in the successful dieters (karate athletes) than non dieting subjects. These results disclose that frontal-parietal responses to "oddball" stimuli depicting enlarged faces (i.e. representing face fattening) are enhanced in successful dieters (karate athletes). Future studies should evaluate this effect in other populations of successful dieters (i.e. boxers, top models etc.)., (Copyright © 2010 Elsevier B.V. All rights reserved.)

It is well known that resting state regional cerebral blood flow is abnormal in obese when compared to normal-weight subjects but the underlying neurophysiological mechanisms are poorly known. To address this issue, we tested the hypothesis that amplitude of resting state cortical electroencephalographic (EEG) rhythms differ among underweight, normal-weight, and overweight/obese subjects as a reflection of the relationship between cortical neural synchronization and regulation of body weight. Eyes-closed resting state EEG data were recorded in 16 underweight subjects, 25 normal-weight subjects, and 18 overweight/obese subjects. All subjects were psychophysically healthy (no eating disorders or major psychopathologies). EEG rhythms of interest were delta (2-4Hz), theta (4-8Hz), alpha 1 (8-10.5Hz), alpha 2 (10.5-13Hz), beta 1 (13-20Hz), beta 2 (20-30Hz), and gamma (30-40Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Statistical results showed that parietal and temporal alpha 1 sources fitted the pattern underweight>normal-weight>overweight/obese (p<0.004), whereas occipital alpha 1 sources fitted the pattern normal-weight>underweight>overweight/obese (p<0.00003). Furthermore, amplitude of the parietal, occipital, and temporal alpha 2 sources was stronger in the normal-weight subjects than in the underweight and overweight/obese subjects (p<0.0007). These results suggest that abnormal weight in healthy overweight/obese subjects is related to abnormal cortical neural synchronization at the basis of resting state alpha rhythms and fluctuation of global brain arousal., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: A previous electroencephalographic (EEG) study has shown that obese subjects are characterized by reduced attention frontal responses to food images, thus raising the hypothesis of attention deficits associated with abnormal body weight (Babiloni et al., 2009a,b). In this line, here we tested the hypothesis of reduced attention cortical responses in underweight subjects., Methods: EEG data were recorded in 16 normal-weight and 16 underweight subjects during an "oddball" paradigm. The subjects were given frequent (70%) and rare (30%) stimuli depicting faces (FACE), food (FOOD), and landscapes (CONTROL), and clicked the mouse after the rare stimuli. These stimuli depicted the same frequent stimuli graphically dilated by 25% along the horizontal axis. Cortical attention responses were probed by the difference between positive event-related potentials peaking around 400-500 ms post-stimulus for the rare minus frequent stimuli (P300). Low resolution electromagnetic source tomography (LORETA) estimated P300 sources., Results: In the FACE condition, the amplitude of prefrontal (Brodmann area: BA10 and BA11) and tempo-parietal (BA19, BA20, BA21, BA22, BA36, BA37, BA39, BA40) sources was lower in the underweight than normal-weight subjects., Conclusions: These results suggest that anterior-posterior cortical attention processes to face images declined in underweight subjects., Significance: The present study motivates future research evaluating if this mechanism is related to a poor judgment about body shape., (Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Is conscious perception of emotional face expression related to enhanced cortical responses? Electroencephalographic data (112 channels) were recorded in 15 normal adults during the presentation of cue stimuli with neutral, happy or sad schematic faces (duration: "threshold time" inducing about 50% of correct recognitions), masking stimuli (2 s), and go stimuli with happy or sad schematic faces (0.5 s). The subjects clicked left (right) mouse button in response to go stimuli with happy (sad) faces. After the response, they said "seen" or "not seen" with reference to previous cue stimulus. Electroencephalographic data formed visual event-related potentials (ERPs). Cortical sources of ERPs were estimated by LORETA software. Reaction time to go stimuli was generally shorter during "seen" than "not seen" trials, possibly due to covert attention and awareness. The cue stimuli evoked four ERP components (posterior N100, N170, P200, and P300), which had similar peak latency in the "not seen" and "seen" ERPs. Only N170 amplitude showed differences in amplitude in the "seen" versus "not seen" ERPs. Compared to the "not seen" ERPs, the "seen" ones showed prefrontal, premotor, and posterior parietal sources of N170 higher in amplitude with the sad cue stimuli and lower in amplitude with the neutral and happy cue stimuli. These results suggest that nonconscious and conscious processing of schematic emotional facial expressions shares a similar temporal evolution of cortical activity, and conscious processing induces an early enhancement of bilateral cortical activity for the schematic sad facial expressions (N170)., (© 2010 Wiley-Liss, Inc.)

It has been shown that concomitant painful stimulation and simple movement at the same hand is related to decreased anticipatory alpha event-related desynchronization (ERD) and reduced pain intensity, possibly due to the interference between somatosensory and motor information processing (Babiloni et al. [6]). Here, we tested the hypothesis that such interference also affects motor performance during sequential movements. Visual warning stimuli were followed by imperative stimuli associated to electrical painful stimulation at left or right middle finger; imperative stimuli triggered motor sequences with right index finger. Electroencephalographic data (N=10, 128 electrodes) were spatially enhanced by surface Laplacian transformation. Cortical activity as revealed by the alpha event-related desynchronization (ERD) was compared in "Pain+ipsilateral movement" condition (movements and painful stimuli performed at the right hand) vs. "Pain+contralateral movement" condition (painful stimuli at left hand and movements performed at the right hand). Results showed that compared with the "Pain+contralateral movement" condition, the "Pain+ipsilateral movement" condition induced lower anticipatory alpha ERD (about 10-12 Hz) in left sensorimotor area, lower subjective pain rate, and delayed movement initiation at the group level. These findings suggest that anticipatory alpha rhythms may underlie cortical preparatory sensorimotor processes preceding somatosensory painful and the initiation of sequential motor events occurring at unilateral or bilateral hand., (Copyright 2009 Elsevier Inc. All rights reserved.)

Here we tested two working hypotheses on spatially selective cortical activation ("neural efficiency") in experts: (i) compared to non-athletes, elite karate athletes are characterized by a reduced cortical activation during the judgment of karate actions; (ii) compared to non-athletes and elite karate athletes, amateur karate athletes are characterized by an intermediate cortical activation during the judgment of karate actions. Electroencephalographic (EEG) data were recorded in 16 elite karate athletes, 15 amateur athletes and 17 non-athletes. They observed a series of 120 karate videos. At the end of each video, the subjects had to judge the technical/athletic level of the exercise by a scale from 0 to 10. The mismatch between their judgment and that of the coach indexed the degree of action judgment. The EEG cortical sources were estimated by sLORETA. With reference to a pre-stimulus period, the power decrease of alpha (8-12 Hz) rhythms during the video indexed the cortical activation (event-related desynchronization, ERD). Regarding the hypothesis of reduced activity in elite karate athletes, low- and high-frequency alpha ERD was less pronounced in dorsal and "mirror" pathways in the elite karate athletes than in the non-athletes. Regarding the hypothesis of intermediate cortical activity in amateur karate athletes, low- and high-frequency alpha ERD was less pronounced in dorsal pathways across the non-athletes, the amateur karate athletes, and the elite karate athletes. In conclusion, athletes' judgment of observed sporting actions is related to less pronounced alpha ERD, as a possible index of "neural efficiency" in experts engaged in social cognition., (Copyright 2009 Elsevier B.V. All rights reserved.)

Objective: It has been reported that GSM electromagnetic fields (GSM-EMFs) of mobile phones modulate--after a prolonged exposure--inter-hemispheric synchronization of temporal and frontal resting electroencephalographic (EEG) rhythms in normal young subjects [Vecchio et al., 2007]. Here we tested the hypothesis that this effect can vary on physiological aging as a sign of changes in the functional organization of cortical neural synchronization., Methods: Eyes-closed resting EEG data were recorded in 16 healthy elderly subjects and 5 young subjects in the two conditions of the previous reference study. The GSM device was turned on (45 min) in one condition and was turned off (45 min) in the other condition. Spectral coherence evaluated the inter-hemispheric synchronization of EEG rhythms at the following bands: delta (about 2-4 Hz), theta (about 4-6 Hz), alpha 1 (about 6-8 Hz), alpha 2 (about 8-10 Hz), and alpha 3 (about 10-12 Hz). The aging effects were investigated comparing the inter-hemispheric EEG coherence in the elderly subjects vs. a young group formed by 15 young subjects (10 young subjects of the reference study; Vecchio et al., 2007)., Results: Compared with the young subjects, the elderly subjects showed a statistically significant (p<0.001) increment of the inter-hemispheric coherence of frontal and temporal alpha rhythms (about 8-12 Hz) during the GSM condition., Conclusions: These results suggest that GSM-EMFs of a mobile phone affect inter-hemispheric synchronization of the dominant (alpha) EEG rhythms as a function of the physiological aging., Significance: This study provides further evidence that physiological aging is related to changes in the functional organization of cortical neural synchronization., (Copyright (c) 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

The present electroencephalographic (EEG) study tested the working hypothesis that the amplitude of resting state cortical EEG rhythms (especially alpha, 8-12 Hz) was higher in elite athletes compared with amateur athletes and non-athletes, as a reflection of the efficiency of underlying back-ground neural synchronization mechanisms. Eyes closed resting state EEG data were recorded in 16 elite karate athletes, 20 amateur karate athletes, and 25 non-athletes. The EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Statistical results showed that the amplitude of parietal and occipital alpha 1 sources was significantly higher in the elite karate athletes than in the non-athletes and karate amateur athletes. Similar results were observed in parietal and occipital delta sources as well as in occipital theta sources. Finally, a control confirmatory experiment showed that the amplitude of parietal and occipital delta and alpha 1 sources was stronger in 8 elite rhythmic gymnasts compared with 14 non-athletes. These results supported the hypothesis that cortical neural synchronization at the basis of eyes-closed resting state EEG rhythms is enhanced in elite athletes than in control subjects.

This study tested the two following hypotheses: (i) compared with non-athletes, elite athletes are characterized by a reduced cortical activation during the preparation of precise visuo-motor performance; (ii) in elite athletes, an optimal visuo-motor performance is related to a low cortical activation. To this aim, electroencephalographic (EEG; 56 channels; Be Plus EB-Neuro) data were recorded in 18 right-handed elite air pistol shooters and 10 right-handed non-athletes. All subjects performed 120 shots. The EEG data were spatially enhanced by surface Laplacian estimation. With reference to a baseline period, power decrease/increase of alpha rhythms during the preshot period indexed the cortical activation/deactivation (event-related desynchronization/synchronization, ERD/ERS). Regarding the hypothesis (i), low- (about 8-10 Hz) and high-frequency (about 10-12 Hz) alpha ERD was lower in amplitude in the elite athletes than in the non-athletes over the whole scalp. Regarding the hypothesis (ii), the elite athletes showed high-frequency alpha ERS (about 10-12 Hz) larger in amplitude for high score shots (50%) than for low score shots; this was true in right parietal and left central areas. A control analysis confirmed these results with another indicator of cortical activation (beta ERD, about 20 Hz). The control analysis also showed that the amplitude reduction of alpha ERD for the high compared with low score shots was not observed in the non-athletes. The present findings globally suggest that in elite athletes (experts), visuo-motor performance is related to a global decrease of cortical activity, as a possible index of spatially selective cortical processes ("neural efficiency").

Objective: Are obese subjects characterized by a reduction of attentional cortical responses to the enlargement of food or body images?, Methods: Electroencephalographic data were recorded in 19 obese and 15 normal-weight adults during an "oddball" paradigm. The subjects were given frequent (70%) and rare (30%) stimuli depicting faces (FACE), food (FOOD), and landscapes (CONTROL), and clicked the mouse after the rare stimuli. These stimuli depicted the same frequent stimuli graphically dilated by 25% along the horizontal axis. Bioelectrical impedance indexed subjects' body fat percentage. Cortical attentional responses were probed by the difference between positive event-related potentials peaking around 400-500ms post-stimulus for the rare minus frequent stimuli (P300). Low resolution electromagnetic source tomography (LORETA) estimated P300 sources., Results: In the FOOD condition, the amplitude of medial prefrontal P300 sources (Brodmann area 9) was lower in the obese than normal-weight subjects, and there was a negative correlation between the body fat percentage and the amplitude of these sources in all subjects as a single group., Conclusions: These results disclose that prefrontal attentional processes to food size are abnormal in obese subjects., Significance: The present study motivates future research evaluating the effects of cognitive rehabilitation in obese subjects.

Objective: Here we tested the hypothesis that in normal weight subjects, attentional cortical responses to the enlargement of faces are related to features of body weight, as a basis for future studies on the role of neurocognitive mechanisms in eating and weight disorders., Methods: Electroencephalographic data were recorded in 15 normal weight adults during a visual "oddball" paradigm. The subjects were given frequent (70%) and rare (30%) stimuli depicting faces (FACE), food (FOOD), and landscapes (CONTROL). The task was to click the mouse after the rare stimuli. These stimuli depicted the same frequent stimuli graphically dilated by 25% along the horizontal axis. Analysis of bioelectrical impedance indexed subjects' body fat percentage. Cortical attentional responses were probed by the difference between positive event-related potentials peaking around 200-600 ms post-stimulus for the frequent minus rare stimuli (P300). LORETA estimated P300 cortical sources., Results: Main results showed that in the FACE condition, there was a negative correlation between the body fat percentage and the reaction time to the rare stimuli, and a positive correlation between the body fat percentage and the amplitude of prefrontal P300 sources (p<0.05)., Conclusions: These results disclose a relationship between body fat and prefrontal attentional processes to body image in normal weight adults., Significance: The present study motivates future research testing the hypothesis that this relationship might be altered in patients with eating and weight disorders.

Objective: Non-steroidal anti-inflammatory drugs such as ibuprofen have a protective role on risk of Alzheimer's disease (AD). Here we evaluated the hypothesis that long-term ibuprofen treatment affects cortical sources of resting electroencephalographic (EEG) rhythms in mild AD patients., Methods: Twenty-three AD patients (13 treated AD IBUPROFEN; 10 untreated AD PLACEBO) were enrolled. Resting EEG data were recorded before and 1 year after the ibuprofen/placebo treatment. EEG rhythms were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). LORETA was used for EEG source analysis., Results: In the AD PLACEBO group, amplitude of delta sources was globally greater at follow-up than baseline. Instead, amplitude of delta sources remained stable or decreased in the majority of the AD IBUPROFEN patients. Clinical (CDR) but not global cognitive status (MMSE) reflected EEG results., Conclusions: These results suggest that in mild AD patients, a long-term ibuprofen treatment slightly slows down the progressive increment of delta rhythms as a sign of contrast against the neurodegenerative processes., Significance: They motivate future investigations with larger population and extended neuropsychological testing, to study the relationships among ibuprofen treatment, delta cortical sources, and higher order functions.

The present study tested the two following hypotheses: (i) compared to non-athletes, elite athletes are characterized by a reduced cortical activation during the judgment of sporting observed actions; (ii) in elite athletes, a good judgment of observed sporting actions is related to a low cortical activation. To address these issues, electroencephalographic (EEG) data were recorded in 15 elite rhythmic gymnasts and 13 non-gymnasts. They observed a series of 120 rhythmic gymnastic videos. At the end of each video, the subjects had to judge the artistic/athletic level of the exercise by a scale from 0 to 10. The mismatch between their judgment and that of the coach indexed the degree of action judgment. The EEG cortical sources were estimated by sLORETA. With reference to a pre-stimulus period, the power decrease of alpha (8-12 Hz) rhythms during the videos indexed the cortical activation (event related desynchronization, ERD). Regarding the hypothesis (i), low- and high-frequency alpha ERD was lower in amplitude in the elite rhythmic gymnasts compared to the non-gymnasts in occipital and temporal areas (ventral pathway) and in dorsal pathway. Regarding the hypothesis (ii), in the elite rhythmic gymnasts high-frequency alpha ERD was higher in amplitude with the videos characterized by a high judgment error than those characterized by a low judgment error; this was true in inferior posterior parietal and ventral premotor areas ("mirror" pathway). These results globally suggest that the judgment of observed sporting actions is related to low amplitude of alpha ERD, as a possible index of spatially selective cortical activation ("neural efficiency").

Objective: High power of pre-stimulus cortical alpha rhythms (about 8-12 Hz) underlies conscious perception in normal subjects. Here we tested the hypothesis that these rhythms are abnormal in persistent vegetative state (PVS) patients, who are awake but not aware of self and environment., Methods: Clinical and resting-state, eyes-closed electroencephalographic (EEG) data were taken from a clinical archive. These data were recorded in 50 PVS subjects (level of cognitive functioning--LCF score: I-II) and in 30 cognitively normal subjects. Rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). Cortical sources were estimated by low-resolution electromagnetic tomography (LORETA). Based on LCF score at 3-months follow-up, PVS patients were retrospectively divided into three groups: 30 subjects who did not recover (NON-REC patients; follow-up LCF: I-II), 8 subjects classified as minimally conscious state patients (MCS patients; follow-up LCF: III-IV), and 12 subjects who recovered (REC patients; follow-up LCF: V-VIII)., Results: Occipital source power of alpha 1 and alpha 2 was high in normal subjects, low in REC patients, and practically null in NON-REC patients. A Cox regression analysis showed that the power of alpha source predicted the rate of the follow up recovery, namely the higher its power, the higher the chance to recover consciousness. Furthermore, the MCS patients showed intermediate values of occipital alpha source power between REC and NON-REC patients., Conclusions: These results suggest that cortical sources of alpha rhythms are related to the chance of recovery at a 3-months follow-up in patients in persistent vegetative state., Significance: Cortical sources of resting alpha rhythms might predict recovery in PVS patients.

Unlabelled: We tested whether cortical activation anticipating painful stimuli is reduced more by integrative processes on somatosensory painful and motor information relative to the same hand than when that information refers to different hands. In 3 conditions, visual warning stimuli were followed by visual target stimuli associated with an electrical painful stimulation at left index finger. In the Pain (control) condition, no task was required after the target stimuli. In the "Pain + ipsilateral movement" condition, the subjects had to perform a movement of the left index finger. In the "Pain + contralateral movement" condition, they had to perform a movement of the right index finger. Meanwhile, electroencephalographic data were recorded (n = 18) from 128 scalp electrodes. Off line, these data were spatially enhanced by surface Laplacian transformation. Sensorimotor cortical activation before the painful stimulation was probed by the percentage power reduction of alpha rhythms at approximately 8 to 12 Hz (event-related desynchronization, ERD). Results showed that the subjects perceived a lower stimulus intensity in both "Pain + ipsilateral" and "Pain + contralateral" conditions compared with the control "Pain" condition. Furthermore, wide anticipatory alpha ERD (approximately 10-12 Hz) was lower in amplitude in the "Pain + ipsilateral" than in the "Pain + contralateral" condition. These results suggest that modulation of alpha rhythms is a putative physiological mechanism underlying anticipatory processes preceding the integration of painful and motor information at cortical level. Furthermore, these processes show a marked interference ("gating") when the sensorimotor integration refer to the same hand as opposed to both hands., Perspective: We showed that cortical alpha rhythms preceding painful stimulation are influenced by the preparation of contralateral and ipsilateral finger movements. These results motivate further investigation for testing the hypothesis that chronic pain patients might exaggerate the anticipatory activation of sensorimotor cortex to negligible pain stimuli.

Background and Objectives: In carriers of the factor V (FV) Leiden mutation, different trans-acting gene variants (HR2 haplotype and FV Cambridge mutation) affect activated protein C (APC) sensitivity. Among a series of FV gene variants characterized, the Asp79His polymorphism appeared to be a good candidate for the modulation of FV activity., Design and Methods: In a group of 150 apparently healthy subjects without the FV Leiden mutation and in 55 apparently healthy subjects with mutation, genotypes of the Asp79His polymorphism and of the HR haplotype were characterized and plasma levels of FV coagulant activity and APC ratios evaluated., Results: In the group without the FV Leiden mutation, 16 subjects (10.7%) carried the His 79 allele and 15 subjects (10.0%) the HR2 haplotype. Two of them carried both gene variants. As compared to FV activity levels in non-carriers (106.4+18.5%), values were lower in subjects with the His79 allele (95.2+25.2%; p=0.025) and in those with the HR2 haplotype (93.7+16.2%; p =0.007). FV activity levels were further reduced in carriers of both FV gene variants (78.7+3.3%; p =0.009). APC values were similar among individuals carrying different FV genotypes. In the group with the FV Leiden mutation, APC ratios were lower in subjects carrying the His 79 allele (0.63; p =0.008) or the HR2 haplotype (0.63; p =0.026) than in subjects without (0.69) reflecting FV activity values., Interpretation and Conclusions: Present data suggest that carriership of the His79 allele modulate plasma levels of FV coagulant activity and, in subjects carrying the FV Leiden mutation, affects APC sensitivity.

The biosynthesis of the zinc finger transcription factor Egr-1 is stimulated by many extracellular signaling molecules including hormones, neurotransmitters, growth and differentiation factors, and cytotoxic metabolites. The 5'-flanking region of the Egr-1 gene contains genetic elements that are essential in connecting stimulation of the cells with enhanced transcription of the Egr-1 gene, and subsequently, transcription of Egr-1-responsive genes. Thus, Egr-1 links cellular signaling cascades with changes in the gene expression pattern. Many biological functions have been attributed to Egr-1. Here, we discuss evidence for Egr-1 control of cellular proliferation and programmed cell death., (Copyright 2002 Wiley-Liss, Inc.)

Nitric oxide (NO) is cytotoxic for human SH-SY5Y neuroblastoma cells. While nuclear condensation was visible in cells treated with nitric oxide donors, we observed that the plasma membrane remained intact, indicating that NO induced apoptotic cell death. We analyzed the NO-induced apoptotic signaling cascade in SH-SY5Y cells and observed a striking increase in early growth response (Egr)-1 promoter activity as a result of NO-induced cell death. Likewise, we detected an activation of the transcriptional activation potential of the ternary complex factor Elk1, a key transcriptional regulator of serum response element-driven gene transcription. Egr-1 is a zinc finger transcription factor that couples extracellular signals to long-term responses by altering expression of Egr-1 target genes. The Egr-1 5'-flanking region contains five serum response elements (SRE) that function as genetic elements for stimulus-transcription coupling. Moreover, these SREs are binding sites for Elk1, suggesting that NO activated Egr-1 gene transcription via activation of Elk1. The NO-induced biosynthesis of Egr-1 was confirmed by Western blot analysis and an NO-dependent increase in the transcriptional activation potential of Egr-1 was observed. The fact that NO-induced neuronal cell death is accompanied by the biosynthesis of Egr-1 suggests that Egr-1 may be an integral part of the NO triggered apoptotic signaling cascade., (Copyright 2002 Wiley-Liss, Inc.)

The activator protein 1 (AP-1) transcription factor is composed of heterodimers of the Fos/activating transcription factor (ATF) and Jun subfamilies of basic-region leucine-zipper (B-ZIP) proteins. In order to determine the identities of individual B-ZIP proteins in various AP-1 complexes we tested the effect of dominant-negative mutants to the B-ZIP proteins c-Fos, ATF2, ATF4 and CCAAT-enhancer-binding protein (C/EBP) on the activities of the collagenase and c-Jun promoters. These dominant-negative mutants inhibit DNA binding of wild-type B-ZIP proteins in a leucine-zipper-dependent fashion. Transcription of a collagenase promoter/reporter gene was induced in HepG2 hepatoma cells by expression of c-Fos and c-Jun, administration of PMA ("TPA") or by expression of a truncated form of MEK (mitogen-activated/extracellular-signal-regulated kinase kinase) kinase-1, MEKK1Delta. In all cases, the dominant-negative mutants A-Fos and A-ATF2 decreased collagenase promoter activity. However, A-ATF4 and A-C/EBP had no effect. A-Fos and A-ATF2 also reduced MEKK1Delta-induced stimulation of the c-Jun promoter. In contrast, constitutive c-Jun promoter activity was blocked solely by A-ATF2, strongly suggesting that ATF2 and/or an ATF2-dimerizing protein are of major importance for c-Jun transcription in unstimulated cells. These results demonstrate that AP-1 transcription factors of different compositions control c-jun gene transcription in resting or stimulated cells.

Research on the regulation of transcription in mammals has focused in recent years mainly on the mechanism of transcriptional activation. However, transcriptional repression mediated by repressor proteins is a common regulatory mechanism in mammals and might play an important role in many biological processes. To understand the molecular mechanism of transcriptional repression, the activity of eight mammalian repressors or repressor domains was investigated using a set of model promoters in combination with two different transcriptional detection methods. The repressors studied were: REST, the thyroid hormone receptors alpha and beta, the zinc finger protein NK10 containing a 'krüppel-associated box' (KRAB), repressor domains derived from the proteins Egr-1, Oct2A and Dr1 and the repressor/activator protein YY1. Here we show that the repressor domains of REST, Egr-1, the thyroid hormone receptors alpha< and beta and NK10 were transferable to a heterologous DNA-binding domain and repressed transcription from proximal and distal positions. Moreover, these repressor domains also blocked the activity of a strong viral enhancer in a 'remote position'. Thus, these domains are 'general' transcriptional repressor domains. The 'krüppel-associated box' was the most powerful repressor domain tested. In contrast, the repressor domains derived from Oct2A and Dr1 were inactive when fused to a heterologous DNA-binding domain. The repressor domain of YY1 exhibited transcriptional repression activity only in one of the transcriptional assay systems. The recruitment of histone deacetylases to the proximity of the basal transcriptional apparatus was recently discussed as a mechanism for some mammalian transcriptional repressor proteins. Here we show here that histone deacetylase 2, targeted to the reporter gene via DNA-protein interaction, functions as a transcriptional repressor protein regardless of the location of its binding site within the transcription unit.

Corticotropin-releasing factor (CRF), a neuropeptide of 41 amino acids, acts as the major physiological regulator of the basal and stress-induced release of corticotropin (ACTH), beta-endorphin and other proopiomelanocortin-derived peptides from the anterior pituitary gland. In addition to its endocrine activity, CRF displays extrahypophysiotropic effects, mainly as a regulator of stress responses. We show here that CRF may additionally function as a differentiating factor in immortalized noradrenergic neuronal CATH.a cells that express CRF receptor type I and resemble locus coeruleus-derived neurons. CRF triggers morphological changes in CATH.a cells including the appearance of extended long, slender neurites with prominent growth cones. CRF-treated CATH.a cells exhibit a morphology similar to locus coeruleus neurons in primary culture. CRF-induced neurite outgrowth of CATH.a cells was blocked by addition of inhibitors for cAMP-dependent protein kinase or extracellular signal-regulated protein kinase (ERK), a subtype of the mitogen-activated protein kinases. The participation of ERK within the CRF signalling cascade was further confirmed by Western blot experiments, with antibodies directed against the phosphorylated form of ERK, and also with transcription-based assays. We conclude that CRF functions as a differentiating factor of CATH.a cells via the cAMP and the MAP kinase signalling pathways.

The transcription factor cAMP response element binding protein 2 (CREB2) belongs to a family of proteins containing a basic region as DNA-binding domain and a leucine zipper as a dimerization domain in its C-terminus. Using indirect immunofluorescence labeling of cells we show that CREB2 is a nuclear protein. To identify the signal(s) required for nuclear targeting of CREB2, various domains of the protein were expressed in COS cells as fusion proteins with glutathione S-transferase and their cellular location assayed by indirect immunofluorescence using antibodies directed against the glutathione S-transferase moiety of the fusion proteins. The results show that the nuclear targeting signal is located in the C-terminal part of the molecule. Deletion mutagenesis revealed that the basic region of CREB2, encompassing amino acids 280 to 300, is sufficient for sorting CREB2 to the nucleus. Single point mutations of basic amino acids within the basic region of CREB2 identified the sequence KKLKK (amino acids 280 to 284) as important for nuclear targeting. Thus, the basic region of CREB2 is necessary not only for tethering CREB2 to DNA but also for sorting CREB2 to the nucleus. However, sequences outside the basic region are additionally required for efficient nuclear sorting of CREB2.

The distribution and biochemical features of the synapsin-like peptides recognized in Aplysia and Helix by various antibodies directed against mammalian synapsins were studied. The peptides can be extracted at low pH and are digested by collagenase; further, they can be phosphorylated by both protein kinase A and Ca2+/calmodulin-dependent protein kinase II. In the ganglia of both snails, they are associated with the soma of most neurons and with the neuropil; punctate immunostaining is present along the neurites. Using cocultures of a Helix serotoninergic neuron and of its target cell, we analysed the redistribution of the synapsin-like peptides during the formation of active synaptic contacts. When the presynaptic neuron is plated in isolation, both synapsin and serotonin immunoreactivities are restricted to the distal axonal segments and to the growth cones; in the presence of the target, the formation of a chemical connection is accompanied by redistribution of the synapsin and serotonin immunoreactivities that concentrate in highly fluorescent round spots scattered along the newly grown neurites located close to the target cell. Almost every spot that is stained for serotonin is also positive for synapsin. In the presynaptic cell plated alone, the number of these varicosity-like structures is substantially stable throughout the whole period; by contrast, when the presynaptic cell synapses the target, their number increases progressively parallel to the increase in the mean amplitude of cumulative excitatory postsynaptic potentials recorded at the same times. The data indicate that mollusc synapsin-like peptides to some extent resemble their mammalian homologues, although they are not exclusively localized in nerve terminals and their expression strongly correlates with the formation of active synaptic contacts.

The enzyme fructose-1,6-bisphosphate aldolase consists of three isozymes that are expressed in a tissue-specific manner. Using antibodies against aldolase B and C, it is shown that aldolase C is expressed in virtually all neuronal cell lines derived from the central and peripheral nervous system. Recently, experiments with transgenic mice indicated that a (G+C)-rich region of the aldolase C promoter might function as a neuron-specific control element of the rat aldolase C gene [Thomas, M., Makeh, I., Briand, P., Kahn, A. & Skala, H. (1993) Eur. J. Biochem. 218, 143-151). To functionally analyse this element, a plasmid consisting of four copies of this (G+C)-rich sequence, a TATA box, and the rabbit beta-globin gene as reporter was constructed. This plasmid was transfected into neuronal and nonneuronal cell lines and transcription was monitored by RNase protection mapping of the beta-globin mRNA. It is shown that the (G+C)-rich element of the aldolase C promoter directs transcription in neuronal as well as in nonneuronal cells. In contrast, the synapsin I promoter, used as a control for neuron-specific gene expression, directed transcription only in neuronal cells. In gel-retardation assays, two major DNA-protein complexes were detected with the (G+C)-rich element of the aldolase C promoter used as a DNA probe and nuclear extracts from brain and liver as a source for DNA-binding proteins. These DNA-proteins interactions could be impaired by a DNA probe that contained an Sp1-binding site, indicating that Sp1 or an Sp1-related factor binds to the aldolase C promoter (G+C)-rich element. This was confirmed by supershift analysis with antibodies specific for Sp1. The zinc finger transcription factor zif268/egr-1, also known to recognize a (G+C)-rich consensus site, did not, however, bind to the (G+C)-rich motif of the aldolase C promoter, nor could it stimulate transcription in transactivation assays from this control region. From these data, we conclude that the (G+C)-rich element of the aldolase C promoter functions as a constitutive transcriptional response element mediated by Sp1 and Sp1-related transcription factors.

Secretogranin II is an acidic secretory protein with a widespread distribution in secretory granules of neuronal and endocrine cells. The secretogranin II gene contains, like other members of the granin family, a cAMP response element (CRE) in its upstream region. To investigate the functional significance of this motif, intracellular cAMP levels were increased in a neuronal cell line derived from the septal region of the brain and the level of secretogranin II gene expression was analysed. It was found that increased cAMP levels did, in fact, induce secretogranin II gene expression. To analyse the cis-acting sequence responsible for this induction, a hybrid gene containing the upstream region of the mouse secretogranin II gene fused to beta-globin as a reporter was constructed. Transfection analysis revealed that cAMP-induced transcription of the secretogranin II promoter/beta-globin gene in septal and insulinoma cells. DNA-protein binding assays showed that recombinant CRE-binding protein (CREB), produced in bacteria or human cells, bound in a sequence-specific manner to the secretogranin II promoter CRE. Moreover, deletion mutagenesis revealed that the CRE motif is a bifunctional genetic regulatory element in that it mediates basal as well as cAMP-stimulated transcription. Interestingly, cAMP had no effect upon secretogranin II gene transcription in PC12 and neuroblastoma cells. An increase in the intracellular cAMP concentration activated a GAL4-CREB fusion protein upon transcription in neuroblastoma cells indicating the integrity of the cAMP signaling pathway to the nucleus. Basal as well as cAMP-stimulated transcription, directed from the secretogranin II promoter was, however, impaired in insulinoma cells by overexpression of CREB-2, a negative-acting CRE-binding protein. These results indicate that competitive effects are likely to occur between CRE-bound transcriptional activators and repressors. We conclude that cAMP-stimulated induction of secretogranin II gene transcription is mediated by the CRE motif in a cell-type-specific manner, and is likely to depend on the balance between positive and negative CRE-binding proteins in a particular cell type.

cAMP has neutrotrophic effects in the nervous system. We have investigated whether there is a correlation between cAMP-induced neurite outgrowth and induction of chromogranin B and synapsin I gene expression. These genes encode marker proteins of distinct populations of vesicles in neurons, neuroendocrine and endocrine cells, and in addition, they contain a cAMP response element (CRE) in their upstream regions, making it likely that cAMP-induced neuronal differentiation might be accompanied by increased transcription of these genes. We increased intracellular cAMP levels in neuronal and neuroendocrine cells and analyzed the levels of chromogranin B and synapsin I mRNA. Our data revealed that, while chromogranin B mRNA was in fact induced following cAMP stimulation, synapsin I mRNA was not affected. To analyze the cis-acting sequences, we constructed hybrid genes containing the upstream region of the mouse chromogranin B gene fused to a reporter gene. Similar plasmids containing the synapsin I or the glucagon promoter were constructed. Transfections of neuronal and endocrine cells, together with deletion mutagenesis, revealed that the CRE of the chromogranin B gene mediated the effect of cAMP upon transcription. This effect was mimicked by overexpression of the catalytic subunit of the cAMP-dependent protein kinase. In addition, overexpression of the negative-acting CRE-binding protein CREB-2 revealed that the chromogranin B CRE functions as a bifunctional genetic regulatory element in that it mediates basal as well as cAMP-stimulated transcription. Synapsin I gene expression, however, was not induced by either elevated intracellular cAMP concentration or by overexpression of protein kinase A, although a similar pattern of proteins, including CREB, bound to the synapsin I and chromogranin B CRE in vitro. Thus while the CRE element in the chromogranin B gene promoter is responsive to cAMP, the same element, when present in the synapsin I promoter, does not confer cAMP inducibility.

Cerebrospinal fluid (CSF)/serum concentration gradients (Q) of individual proteins (albumin, IgG, alpha 2-macroglobulin) have been studied in controls and in patients in whom the lumbar CSF flow is altered (medullary compression) or the blood-CSF barrier (BCB) function impaired (acute idiopathic polyneuropathy and acute meningoencephalitis). The analysis of relationships among protein Q has been performed by total and multiple regressions and the actual BCB permeability to individual proteins has been interpreted according to the accepted theoretical porous or vesicular BCB models. The exponential Q-IgG vs. Q-albumin total regression, and the poor Q-alpha 2-macroglobulin vs. Q-albumin regression found in controls, together with the different multiple regressions among proteins and the high Q-IgG vs. Q-albumin partial regression coefficients found in medullary compression, acute idiopathic polyneuropathy and acute meningoencephalitis, indicated that different permeability mechanisms can be postulated. Heterogeneous, fairly independent permeability BCB mechanisms maintain the normal CSF/serum protein concentration gradient. Pinocytotic vesicles or pores of radius exceeding 1000-1500 A, probably located at the capillary endothelium, account for the main serum-derived CSF protein fraction(s) with large hydrodynamic radius (R). A more selective endothelial vesicular transport with a radius of 250 A transfers a negligible amount of protein from serum into CSF. Proteins with small R also enter the CSF through a set of selective pores of radius 120 A, probably at the level of the choroidal epithelium. Pinocytotic vesicles with a radius of 250 A and increased rate of formation induce the accumulation of proteins below an obstruction of lumbar CSF flow. An increased formation rate of vesicles with a radius of 450 A can explain the increased capillary permeability in nerve roots in acute idiopathic polyneuropathy. Loss of selectivity was the main feature of BCB in acute meningoencephalitis, and it seemed to be due to pores or vesicles with a radius larger than 1000-1500 A. The heterogeneity of BCB mechanisms must be taken into account when the intrathecal synthesis of a protein, also derived from serum (for example IgG), has to be measured.