Slow Resting State Fluctuations Enhance Neuronal and Behavioral Responses to Looming Sounds.

We investigate both experimentally and using a computational model how the power of the electroencephalogram (EEG) recorded in human subjects tracks the presentation of sounds with acoustic intensities that increase exponentially (looming) or remain constant (flat). We focus on the link between this EEG tracking response, behavioral reaction times and the time scale of fluctuations in the resting state, which show considerable inter-subject variability. Looming sounds are shown to generally elicit a sustained power increase in the alpha and beta frequency bands. In contrast, flat sounds only elicit a transient upsurge at frequencies ranging from 7 to 45 Hz. Likewise, reaction times (RTs) in an audio-tactile task at different latencies from sound onset also present significant differences between sound types. RTs decrease with increasing looming intensities, i.e. as the sense of urgency increases, but remain constant with stationary flat intensities. We define the reaction time variation or "gain" during looming sound presentation, and show that higher RT gains are associated with stronger correlations between EEG power responses and sound intensity. Higher RT gain further entails higher relative power differences between loom and flat in the alpha and beta bands. The full-width-at-half-maximum of the autocorrelation function of the eyes-closed resting state EEG also increases with RT gain. The effects are topographically located over the central and frontal electrodes. A computational model reveals that the increase in stimulus-response correlation in subjects with slower resting state fluctuations is expected when EEG power fluctuations at each electrode and in a given band are viewed as simple coupled low-pass filtered noise processes jointly driven by the sound intensity. The model assumes that the strength of stimulus-power coupling is proportional to RT gain in different coupling scenarios, suggesting a mechanism by which slower resting state fluctuations enhance EEG response and shorten reaction times.

Directional K+ channel insertion in a single phospholipid bilayer: Neutron reflectometry and electrophysiology in the joint exploration of a model membrane functional platform.

We investigated the insertion of small potassium (K+) channel proteins (KcvMA-1D and KcvNTS) into model membranes and the lipid-protein structural interference, combining neutron reflectometry and electrophysiology. Neutron reflectometry experiments showed how the transverse structure and mechanical properties of the bilayer were modified, upon insertion of the proteins in single model-membranes, either supported on solid substrate or floating. Parallel electrophysiology experiments were performed on the same channels reconstituted in free-standing planar lipid bilayers, of both typical composition and matched to the neutron reflectometry experiment, assessing their electrical features. Functional and structural results converge in detecting that the proteins, conical in shape, insert with a directionality, cytosolic side first. Our work addresses the powerful combination of the two experimental approaches. We show here that membrane structure spectroscopy and ion channel electrophysiology can become synergistic tools in the analysis of structural-functional properties of biomimetic complex environment.

A Dynamic Core Network and Global Efficiency in the Resting Human Brain.

Spontaneous brain activity is spatially and temporally organized in the absence of any stimulation or task in networks of cortical and subcortical regions that appear largely segregated when imaged at slow temporal resolution with functional magnetic resonance imaging (fMRI). When imaged at high temporal resolution with magneto-encephalography (MEG), these resting-state networks (RSNs) show correlated fluctuations of band-limited power in the beta frequency band (14-25 Hz) that alternate between epochs of strong and weak internal coupling. This study presents 2 novel findings on the fundamental issue of how different brain regions or networks interact in the resting state. First, we demonstrate the existence of multiple dynamic hubs that allow for across-network coupling. Second, dynamic network coupling and related variations in hub centrality correspond to increased global efficiency. These findings suggest that the dynamic organization of across-network interactions represents a property of the brain aimed at optimizing the efficiency of communication between distinct functional domains (memory, sensory-attention, motor). They also support the hypothesis of a dynamic core network model in which a set of network hubs alternating over time ensure efficient global communication in the whole brain.

Decision and action planning signals in human posterior parietal cortex during delayed perceptual choices.

During simple perceptual decisions, sensorimotor neurons in monkey fronto-parietal cortex represent a decision variable that guides the transformation of sensory evidence into a motor response, supporting the view that mechanisms for decision-making are closely embedded within sensorimotor structures. Within these structures, however, decision signals can be dissociated from motor signals, thus indicating that sensorimotor neurons can play multiple and independent roles in decision-making and action selection/planning. Here we used functional magnetic resonance imaging to examine whether response-selective human brain areas encode signals for decision-making or action planning during a task requiring an arbitrary association between face pictures (male vs. female) and specific actions (saccadic eye vs. hand pointing movements). The stimuli were gradually unmasked to stretch the time necessary for decision, thus maximising the temporal separation between decision and action planning. Decision-related signals were measured in parietal and motor/premotor regions showing a preference for the planning/execution of saccadic or pointing movements. In a parietal reach region, decision-related signals were specific for the stimulus category associated with its preferred pointing response. By contrast, a saccade-selective posterior intraparietal sulcus region carried decision-related signals even when the task required a pointing response. Consistent signals were observed in the motor/premotor cortex. Whole-brain analyses indicated that, in our task, the most reliable decision signals were found in the same neural regions involved in response selection. However, decision- and action-related signals within these regions can be dissociated. Differences between the parietal reach region and posterior intraparietal sulcus plausibly depend on their functional specificity rather than on the task structure.

Framing deductive reasoning with emotional content: an fMRI study.

In the literature concerning the study of emotional effect on cognition, several researches highlight the mechanisms of reasoning ability and the influence of emotions on this ability. However, up to now, no neuroimaging study was specifically devised to directly compare the influence on reasoning performance of visual task-unrelated with semantic task-related emotional information. In the present functional fMRI study, we devised a novel paradigm in which emotionally negative vs. neutral visual stimuli (context) were used as primes, followed by syllogisms composed of propositions with emotionally negative vs. neutral contents respectively. Participants, in the MR scanner, were asked to assess the logical validity of the syllogisms. We have therefore manipulated the emotional state and arousal induced by the visual prime as well as the emotional interference exerted by the syllogism content. fMRI data indicated a medial prefrontal cortex deactivation and lateral/dorsolateral prefrontal cortex activation in conditions with negative context. Furthermore, a lateral/dorsolateral prefrontal cortex modulation caused by syllogism content was observed. Finally, behavioral data confirmed the influence of emotional task-related stimuli on reasoning ability, since the performance was worse in conditions with syllogisms involving negative emotions. Therefore, on the basis of these data, we conclude that emotional states can impair the performance in reasoning tasks by means of the delayed general reactivity, whereas the emotional content of the target may require a larger amount of top-down resources to be processed.

Frequency specific interactions of MEG resting state activity within and across brain networks as revealed by the multivariate interaction measure.

Resting state networks (RSNs) are sets of brain regions exhibiting temporally coherent activity fluctuations in the absence of imposed task structure. RSNs have been extensively studied with fMRI in the infra-slow frequency range (nominally <10(-1)Hz). The topography of fMRI RSNs reflects stationary temporal correlation over minutes. However, neuronal communication occurs on a much faster time scale, at frequencies nominally in the range of 10(0)-10(2)Hz. We examined phase-shifted interactions in the delta (2-3.5 Hz), theta (4-7 Hz), alpha (8-12 Hz) and beta (13-30 Hz) frequency bands of resting-state source space MEG signals. These analyses were conducted between nodes of the dorsal attention network (DAN), one of the most robust RSNs, and between the DAN and other networks. Phase shifted interactions were mapped by the multivariate interaction measure (MIM), a measure of true interaction constructed from the maximization of imaginary coherency in the virtual channels comprised of voxel signals in source space. Non-zero-phase interactions occurred between homologous left and right hemisphere regions of the DAN in the delta and alpha frequency bands. Even stronger non-zero-phase interactions were detected between networks. Visual regions bilaterally showed phase-shifted interactions in the alpha band with regions of the DAN. Bilateral somatomotor regions interacted with DAN nodes in the beta band. These results demonstrate the existence of consistent, frequency specific phase-shifted interactions on a millisecond time scale between cortical regions within RSN as well as across RSNs.

Adding dynamics to the Human Connectome Project with MEG.

The Human Connectome Project (HCP) seeks to map the structural and functional connections between network elements in the human brain. Magnetoencephalography (MEG) provides a temporally rich source of information on brain network dynamics and represents one source of functional connectivity data to be provided by the HCP. High quality MEG data will be collected from 50 twin pairs both in the resting state and during performance of motor, working memory and language tasks. These data will be available to the general community. Additionally, using the cortical parcellation scheme common to all imaging modalities, the HCP will provide processing pipelines for calculating connection matrices as a function of time and frequency. Together with structural and functional data generated using magnetic resonance imaging methods, these data represent a unique opportunity to investigate brain network connectivity in a large cohort of normal adult human subjects. The analysis pipeline software and the dynamic connectivity matrices that it generates will all be made freely available to the research community.

Multidisciplinary lifestyle intervention in the obese: its impact on patients' perception of the disease, food and physical exercise.

BACKGROUND AND AIMS: To be successful, lifestyle intervention in obesity must take into account patients' views. The aim of the present study, conducted using a narrative-autobiographical approach, was to report on the perception of disease, food and physical exercise in a group of 80 obese patients during a structured multidisciplinary lifestyle intervention. METHODS AND RESULTS: Patients underwent lifestyle intervention, of three months' duration, structured in the following steps: 1) an initial medical examination; 2) an interview by a psychologist; 3) an assessment by a dietician, 4) a physical examination by a specialist in sports medicine; 5) an individualized program consisting of 24 sessions (two per week) of structured indoor exercise 6) eight sessions of group therapeutic education; 7) Nordic walking activity combined with walking excursions during weekends. All the narrative autobiographic texts obtained during the lifestyle intervention were submitted for content analysis; data were analysed according to the ''grounded theory'' method. According to patients' descriptions at the end of the intervention, lifestyle intervention resulted in enhanced self-efficacy and a reduction in their dependency on food and people; their fear of change was also diminished because, by undergoing intervention, they had experienced change. CONCLUSION: The findings made in the present qualitative analysis suggest that whenever multidisciplinary lifestyle intervention is planned for patients with obesity, it is of the utmost importance to tailor the approach while taking the following key aspects into account: motivation, barriers and/or facilitators in lifestyle change, patients' perceptions of obesity and relationship with food, diet and exercise.

Comparison of cutaneous termic response to a standardised warm up in trained and untrained individuals.

AIM: Warm up prior to exercise induces an increased production of metabolic heat, which triggers the thermoregulatory system to initiate heat loss mechanisms. Variations in cutaneous tissue temperature have been already reported in trained subjects, by means of high resolution thermal imaging. Purpose of this paper was to quantitatively evaluate, by means of infrared thermography, the differences in the cutaneous temperature among trained and untrained subjects. METHODS: Forty male volunteers performed a standard warm up exercise on a stationary cycle, divided in three steps: 1) 0-5 minutes at 100 Watt; 2) 5-10 minutes at 130 Watt; and 3) 10-15 minutes at 160 Watt. Thermal images from thorax and upper limbs were collected during the exercise. Heart rate was also measured. RESULTS: In comparison to baseline, trained subjects exhibited a significant temperature reduction in the third step (trunk, P<0.01; upper limbs, P<0.009), while no difference was observed in untrained subjects. In the comparison between groups, a statistically significant difference was observed in both regions of interest, in the second (trunk, P<0.01; upper limbs, P<0.02), and in the third step (trunk, P<0.0002; upper limbs, P<0.0008). During the whole exercise, heart rate increased progressively in all participants, but more markedly in untrained subjects. CONCLUSION: Cutaneous thermoregulatory response differs among trained and untrained participants. Infrared thermal imaging is useful in detecting these differences, providing additional data to the physiological evaluation of subjects performing sport activities.

Iloprost treatment summer-suspension: effects on skin thermal properties and cytokine profile in systemic sclerosis patients.

AIM: Aim of the study was to assess whether Iloprost treatment summer suspension modifies systemic cytokines levels, cutaneous thermal properties and functional response to a cold-induced stress in patients affected by systemic sclerosis (SSc). METHODS: Twenty-eight patients fulfilling the American College of Rheumatology (ACR) criteria for SSc were included in the study. Patients recorded number, duration and pain-severity of Raynaud phenomenon (RP). Pain-severity was determined by a visual analog scale. Cytokines expression and production in peripheral blood mononuclear cells and serum were evaluated by RT-PCR and ELISA assay. Basal finger temperature (Tb), distal-dorsal difference temperature (DTdd) and thermal recovery time (tr) from cold stress were measured by means of functional infrared imaging (fIR). Measurements were performed in late spring, during routine Iloprost therapy (1-3 days infusion of 0.5-2 ng/kg every month), and in late summer after a therapy-withdrawal period. RESULTS: Deterioration of SSc patients' skin thermal properties was observed in the period of therapy withdrawal (Tb reduction and tr enhancement; no DTdd differences) despite the improvement in symptoms of RP. A reduction in IL-12/23p40 gene expression was recorded after therapy withdrawal and a direct correlation between IL-12/23p40 and IL-23p19 gene expression was observed, stronger after therapy suspension. CONCLUSION: Our data suggest that Iloprost treatment summer suspension may induce the loss of the therapy beneficial effect on microcirculation despite the objective reduction of RP, thus favouring a continuous use of Iloprost in absence of severe side effects. Iloprost showed to modulate only IL-23 expression corroborating the idea that this cytokine is crucial for SSc development and progression.

Pharmacological functional MRI assessment of the effect of ibuprofen-arginine in painful conditions.

Pharmacological functional magnetic resonance imaging (phMRI) is a valuable tool for the investigation of pharmacological effects of a drug on pain processing. We hypothesized that the ibuprofen-arginine combination, in line with its characteristic analgesic properties, may influence the phMRI response at the central level, as compared to placebo. Ten healthy subjects underwent a double-blind, placebo-controlled, randomized, cross-over phFMRI study with somatosensory painful stimulation of the right median nerve. We measured the blood oxygen level dependent (BOLD) signal variations induced in conditions of pain after oral administration of either ibuprofen-arginine or placebo formulations. Independent component analysis (ICA) was used for the analysis of the fMRI data, without assuming a specific hemodynamic response function (HRF), which may be altered by drug administration. Median nerve electrical painful stimulation mainly activated the primary contralateral and the secondary somatosensory cortices, the insula, the supplementary motor area, and the middle frontal gyrus. Placebo and ibuprofen-arginine administration induced activation bilaterally in the premotor cortex, and an overall reduction in the other pain-related areas, which was more prominent in the left hemisphere. A task-related increase of BOLD signal between drug and placebo was observed bilaterally in the primary somatosensory area and the middle frontal gyrus without any changes in subjective pain scores. Overall, our findings show that ibuprofen-arginine, in line with the characteristic analgesic properties of ibuprofen, influences the BOLD response in specific pain-related brain areas with respect to placebo, with a vasoactive effect possibly due to arginine.

Functional infrared imaging of paroxysmal ischemic events in patients with Raynaud's phenomenon.

The use of thermal infrared (IR) imaging together with the study of the thermal recovery from a controlled cold challenge has been proposed in the diagnosis and follow-up of therapeutic response of Raynaud's Phenomenon (RP) and Systemic Sclerosis (SSc). The controlled cold challenge test usually performed during IR investigations may induce a RP in patients with the latter condition. In our Institution we routinely perform capillaroscopy and thermal IR to follow-up SSc patients. In this paper, we describe the thermal recovery patterns shown by two SSc patients (a 40 year-old male with diffuse variant of SSc and a 71 year-old female with a limited variant of SSc) who presented ischemic and paroxysmal RP attack while recovering from the routine controlled cold challenge test. During RP attack, the cutaneous temperature of some fingers continued to decrease for some minutes even after the cessation of the cold stress. To the best of our knowledge, to date, no literature report has documented the thermal behaviour of SSc patients' fingers which occasionally present ischemic and paroxysmal response. Triggering of ischemic RP attack appears to not rely only on morphological and structural finger impairment, but also upon other aspects, like the emotional attitude of the subject and the possible discomfort experienced with the proceeding of the functional cold stress test.

Multimodal integration of fMRI and EEG data for high spatial and temporal resolution analysis of brain networks.

Two major non-invasive brain mapping techniques, electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), have complementary advantages with regard to their spatial and temporal resolution. We propose an approach based on the integration of EEG and fMRI, enabling the EEG temporal dynamics of information processing to be characterized within spatially well-defined fMRI large-scale networks. First, the fMRI data are decomposed into networks by means of spatial independent component analysis (sICA), and those associated with intrinsic activity and/or responding to task performance are selected using information from the related time-courses. Next, the EEG data over all sensors are averaged with respect to event timing, thus calculating event-related potentials (ERPs). The ERPs are subjected to temporal ICA (tICA), and the resulting components are localized with the weighted minimum norm (WMNLS) algorithm using the task-related fMRI networks as priors. Finally, the temporal contribution of each ERP component in the areas belonging to the fMRI large-scale networks is estimated. The proposed approach has been evaluated on visual target detection data. Our results confirm that two different components, commonly observed in EEG when presenting novel and salient stimuli, respectively, are related to the neuronal activation in large-scale networks, operating at different latencies and associated with different functional processes.

Tonotopic organization of the human auditory cortex.

Neuromagnetic measurements of responses to auditory stimuli consisting of pure tones amplitude-modulated at a low frequency have been used to deduce the location of cortical activity. The evoked field source systematically increased in depth beneath the scalp with increasing frequency of the tone. The tonotopic progression can be described as a logarithmic mapping.

A frontoparietal network for spatial attention reorienting in the auditory domain: a human fMRI/MEG study of functional and temporal dynamics.

Several studies have identified a supramodal network critical to the reorienting of attention toward stimuli at novel locations and which involves the right temporoparietal junction and the inferior frontal areas. The present functional magnetic resonance imaging (fMRI)\magnetoencephalography (MEG) study investigates: 1) the cerebral circuit underlying attentional reorienting to spatially varying sound locations; 2) the circuit related to the regular change of sound location in the same hemifield, the change of sound location across hemifields, or sounds presented randomly at different locations on the azimuth plane; 3) functional temporal dynamics of the observed cortical areas exploiting the complementary characteristics of the fMRI and MEG paradigms. fMRI results suggest 3 distinct roles: the supratemporal plane appears modulated by variations of sound location; the inferior parietal lobule is modulated by the cross-meridian effect; and the inferior frontal cortex is engaged by the inhibition of a motor response. MEG data help to elucidate the temporal dynamics of this network by providing high-resolution time series with which to measure latency of neural activation manipulated by the reorienting of attention.

Empirical Markov Chain Monte Carlo Bayesian analysis of fMRI data.

In this work an Empirical Markov Chain Monte Carlo Bayesian approach to analyse fMRI data is proposed. The Bayesian framework is appealing since complex models can be adopted in the analysis both for the image and noise model. Here, the noise autocorrelation is taken into account by adopting an AutoRegressive model of order one and a versatile non-linear model is assumed for the task-related activation. Model parameters include the noise variance and autocorrelation, activation amplitudes and the hemodynamic response function parameters. These are estimated at each voxel from samples of the Posterior Distribution. Prior information is included by means of a 4D spatio-temporal model for the interaction between neighbouring voxels in space and time. The results show that this model can provide smooth estimates from low SNR data while important spatial structures in the data can be preserved. A simulation study is presented in which the accuracy and bias of the estimates are addressed. Furthermore, some results on convergence diagnostic of the adopted algorithm are presented. To validate the proposed approach a comparison of the results with those from a standard GLM analysis, spatial filtering techniques and a Variational Bayes approach is provided. This comparison shows that our approach outperforms the classical analysis and is consistent with other Bayesian techniques. This is investigated further by means of the Bayes Factors and the analysis of the residuals. The proposed approach applied to Blocked Design and Event Related datasets produced reliable maps of activation.

Hypothalamus, sexual arousal and psychosexual identity in human males: a functional magnetic resonance imaging study.

In a recent functional magnetic resonance imaging study, a complex neural circuit was shown to be involved in human males during sexual arousal [A. Ferretti et al. (2005) Neuroimage, 26, 1086]. At group level, there was a specific correlation between penile erection and activations in anterior cingulate, insula, amygdala, hypothalamus and secondary somatosensory regions. However, it is well known that there are remarkable inter-individual differences in the psychological view and attitude to sex of human males. Therefore, a crucial issue is the relationship among cerebral responses, sexual arousal and psychosexual identity at individual level. To address this issue, 18 healthy male subjects were recruited. Their deep sexual identity (DSI) was assessed following the construct revalidation by M. Olivetti Belardinelli [(1994) Sci. Contrib. Gen. Psychol., 11, 131] of the Franck drawing completion test, a projective test providing, according to this revalidation, quantitative scores on 'accordance/non-accordance' between self-reported and psychological sexual identity. Cerebral activity was evaluated by means of functional magnetic resonance imaging during hard-core erotic movies and sport movies. Results showed a statistically significant positive correlation between the blood oxygen level-dependent signal in bilateral hypothalamus and the Franck drawing completion test score during erotic movies. The higher the blood oxygen level-dependent activation in bilateral hypothalamus, the higher the male DSI profile. These results suggest that, in male subjects, inter-individual differences in the DSI are strongly correlated with blood flow to the bilateral hypothalamus, a dimorphic brain region deeply implicated in instinctual drives including reproduction.

Comparison of thermal infrared and laser doppler imaging in the assessment of cutaneous tissue perfusion in scleroderma patients and healthy controls.

In this study we propose a non-invasive method to calculate blood flow by means of thermal infrared imaging and bio-heat transfer modeling. The method is able to provide high time-resolution series of cutaneous blood flow images with the same spatial resolution of the thermal images. The method was tested against a standard laser Doppler imaging system, which to date is considered the gold standard for non-invasive assessment of cutaneous blood flow, on both healthy subjects and patients suffering from systemic sclerosis (SSc; a pathological condition with microvessel endothelium injury). Twenty healthy subjects and twenty SSc patients simultaneously underwent laser Doppler and thermal imaging of the dorsum of the hand. A linear correlation between perfusion values obtained with the two methods was found for the healthy control group (R = 0.85, Pearson Product Moment Correlation). A significant correlation was not observed for the SSc patient group. The results of this study suggest that combined laser Doppler, thermal imaging and bio-heat transfer modeling could effectively discriminate between healthy vs. impaired conditions of the cutaneous tissue thermal properties and cutaneous vasculature. Such method, in addition to providing a potential effective imaging-based tool for a variety of biomedical and clinical applications ranging from diagnostics to treatment follow-up, may help the understanding of the morphological and functional impairment secondary to the disease. The thermal imaging-based method provided faster and better time-resolved imaging of cutaneous perfusion than standard laser Doppler techniques as the thermal cameras can provide up to 100 complete 524 x 524 pixel images per second, thus allowing real time monitoring of tissue perfusion rates.

14-3-3 proteins regulate the potassium channel KAT1 by dual modes.

KAT1 is a cloned plant potassium channel belonging to the superfamily of Shaker-like Kv channels. Previous studies have shown that 14-3-3 proteins significantly increase KAT1 current by modifying the channel open probability. Employing a 14-3-3 scavenger construct to lower the long-term availability of endogenous 14-3-3 proteins, we found that 14-3-3 proteins not only control the voltage dependency of the channel but also the number of channels in the plasma membrane.

New morphologic variants of the hand motor cortex as seen with MR imaging in a large study population.

BACKGROUND AND PURPOSE: The hand motor cortex (HMC) has been classically described as having an omega or epsilon shape in axial-plane images obtained with CT and MR imaging. The aim of this study was to use MR imaging and Talairach normalization in a large sample population that was homogeneous for age and handedness to evaluate in a sex model a new classification with 5 morphologic variants of the HMC in the axial plane (omega, medially asymmetric epsilon, epsilon, laterally asymmetric epsilon, and null). MATERIALS AND METHODS: Structural brain MR images were obtained from 257 right-handed healthy subjects (143 men and 114 women; mean age, 23.1 +/- 1.1 years) via a Talairach space transformed 3D magnetization-prepared rapid acquisition of gradient echo sequence. The frequencies of the different HMC variants were reported for hemisphere and sex. RESULTS: The new variants of the HMC (medially asymmetric epsilon, laterally asymmetric epsilon, and null) were observed in 2.9%, 7.0%, and 1.8% of the hemispheres, respectively. Statistically significant sex differences were observed: The epsilon variant was twice as frequent in men, and an interhemispheric concordance for morphologic variants was observed only for women. CONCLUSION: The large study population permitted the description of a new morphologic classification that included 3 new variants of the HMC. This new morphologic classification should facilitate the identification of the precentral gyrus in subsequent studies and in everyday practice.