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Reported findings on reactivity to stress of the sympathetic-adreno-medullar (SAM) and hypothalamic-pituitary-adrenal (HPA) systems in panic disorder (PD) are very variable. This inconsistency may be explained by differences in treatment exposure, illness duration and emotion regulation strategies. The present study examined the reactivity to mental stress of the SAM and HPA axes in a sample of first episode, drug naïve patients with PD which avoids confounds of medications exposure and illness chronicity. Activation of the SAM axis was evaluated by dosage of salivary alpha-amylase (sAA) and heart rate. Activation of the HPA axis was tested by dosage of salivary cortisol. Psychological assessments were done by the Self-Rating Depression Scale, the Self-Rating Anxiety Scale, the State-Trait Anxiety Inventory, the Cope Orientation to Problems Experienced (COPE) Inventory and the 16 Personality Factor Questionnaire (16PF). Patients showed reduced sAA stress reactivity, higher baseline cortisol levels and a more rapid decrease in stress cortisol levels as compared with controls. A significant correlation was found between active coping strategies and cortisol levels (response to stress). The findings suggest that blunted SAM stress reactivity and a rapid decrease in stress cortisol levels reflect traits that may enhance vulnerability to psychopathology in patients with PD., (Copyright © 2018 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.) more...

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.) more...

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.) more...

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.) more...

The resting energy expenditure and the adaptation of the autonomic nervous system induced by sport activities in sedentary women and in female professional basketball players have been studied. Resting energy expenditure, body composition and the level of activity of the autonomic nervous system were measured before and after a period of six months. The physical activity induced an increase in resting energy expenditure and free fat mass without variations in body weight. Basketball players showed a significant increase in the parasympathetic activity, measured by the power spectral analysis of the heart rate variability. These findings demonstrate that resting energy expenditure is higher in the athletes than in sedentary women, despite the augmented parasympathetic activity that is usually related to lower energy expenditure., (Copyright © 2012. Published by Elsevier B.V.) more...

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.) more...

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.) more...

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.) more...

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. more...

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. more...

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. more...

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. more...

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. more...

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. more...