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.

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.

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.

Differential diagnosis of Raynaud's phenomenon based on modeling of finger thermoregulation.

Raynaud's phenomenon (RP) is a vasospastic disorder of small arteries, pre-capillary arteries, and cutaneous arteriovenous shunts of the extremities, typically induced by cold exposure and emotional stress. RP is either primary (PRP) or secondary to connective tissue diseases such as systemic sclerosis (SSc). Early differential diagnosis is crucial in order to set the proper therapeutic strategy. To this goal, thermal infrared imaging data from 18 healthy controls (HCs) and 48 RP patients (20 PRP, 28 SSc) were processed through a model for a second-order time-invariant system with exponential critically damped dynamic response. Subject classification on the basis of the model parameters provides 100% true-positive discrimination for RP patients (PRP and SSc) and healthy, and 90% of correct classification within the group of patients. The proposed method may provide useful hints for early differential diagnosis in the assessment of RP disease.

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.

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.

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.

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.

Reorganization of functional connectivity of the language network in patients with brain gliomas.

BACKGROUND AND PURPOSE: fcMRI measures spontaneous and synchronous fluctuations of BOLD signal between spatially remote brain regions. The present study investigated potential LN fcMRI modifications induced by left hemisphere brain gliomas. MATERIALS AND METHODS: We retrospectively evaluated fcMRI in 39 right-handed patients with a left hemisphere brain glioma and 13 healthy controls. Patients and controls performed a verb-generation task to identify individual BOLD activity in the left IFG (Broca area); the active region was used as seed to create whole-brain background connectivity maps and to identify the LN (including bilateral regions of the IFG, STS, and TPJ) following regression of task-evoked activity. We assessed differences between patients and controls in the pattern of functional connectivity of the LN, as well as potential effects of tumor position, histopathology, and volume. RESULTS: Global fcMRI of the LN was significantly reduced in patients with tumor compared with controls. Specifically, fcMRI was significantly reduced within seed regions of the affected hemisphere (left intrahemispheric fcMRI) and between the TPJ of the 2 hemispheres. In patients, the left TPJ node showed the greatest decrease of functional connectivity within the LN. CONCLUSIONS: The presence of a brain tumor in the left hemisphere significantly reduced the degree of fcMRI between language-related brain regions. The pattern of fcMRI was influenced by tumor position but was not restricted to the area immediately surrounding the tumor because the connectivity between remote and contralateral areas was also affected.

Diffusion tensor imaging of subependymal heterotopia.

A magnetic resonance (MR) diffusion tensor imaging (DTI) study was performed in a newborn with bilateral subependymal heterotopia (SE). White matter fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) were compared to values obtained in four newborns with moderate perinatal asphyxia and normal MRI findings. The reduction of FA and increase of AD and RD in the newborn with SE were the in vivo late expression of alterations in the intermediate zone, with an underlying arrest of neuronal migration.

Comparison of hypothesis- and a novel hybrid data/hypothesis-driven method of functional MR imaging analysis in patients with brain gliomas.

BACKGROUND AND PURPOSE: An alternative technique, which is less influenced by tumor- and patient-related factors, is required to overcome the limits of GLM analysis of fMRI data in patients. The aim of this study was to statistically assess differences in the identification of language regions and hemispheric lateralization of language function between controls and patients as estimated by both the GLM and a novel combined ICA-GLM procedure. MATERIALS AND METHODS: We retrospectively evaluated 42 patients with pathologically confirmed brain gliomas of the left frontal and/or temporoparietal lobes and a control group of 14 age-matched healthy volunteers who underwent BOLD fMRI to lateralize language functions in the cerebral hemispheres. Data were processed by using a classic GLM and ICA-GLM. RESULTS: ICA-GLM demonstrated a higher sensitivity in detecting language activation, specifically in the left TPJ of patients. There were no significant differences between the GLM and ICA-GLM in controls; however, statistically significant differences were observed by using ICA-GLM for the LI in patients. For the computation of the LI, ICA-GLM was less influenced by the chosen statistical threshold compared with the GLM. CONCLUSIONS: We suggest the use of the ICA-GLM as a valid alternative to the classic GLM method for presurgical mapping in patients with brain tumors and to replicate the present results in a broader sample of patients.

Functional connectivity MR imaging of the language network in patients with drug-resistant epilepsy.

BACKGROUND AND PURPOSE: Subtle linguistic dysfunction and reorganization of the language network were described in patients with epilepsy, suggesting the occurrence of plasticity changes. We used resting state FC-MRI to investigate the effects induced by chronic epilepsy on the connectivity of the language-related brain regions and correlated it with language performance. MATERIALS AND METHODS: FC-MRI was evaluated in 22 right-handed patients with drug-resistant epilepsy (11 with LE and 11 with RE) and in 12 healthy volunteers. Neuropsychological assessment of verbal IQ was performed. Patients and controls underwent BOLD fMRI with a verb-generation task, and language function was lateralized by an LI. Intrinsic activity fluctuations for FC analysis were extracted from data collected during the task. Six seeding cortical regions for speech in both hemispheres were selected to obtain a measure of the connectivity pattern among the language networks. RESULTS: Patients with LE presented atypical language lateralization and an overall reduced connectivity of the language network with respect to controls. In patients with both LE and RE, the mean FC was significantly reduced within the left (dominant) hemisphere and between the 2 hemispheres. In patients with LE, there was a positive correlation between verbal IQ scores and the left intrahemispheric FC. CONCLUSIONS: In patients with intractable epilepsy, FC-MRI revealed an overall reduction and reorganization of the connectivity pattern within the language network. FC was reduced in the left hemisphere regardless of the epileptogenic focus side and was positively correlated with linguistic performance only in patients with LE.

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.

Elevated response of human amygdala to neutral stimuli in mild post traumatic stress disorder: neural correlates of generalized emotional response.

Previous evidence from functional magnetic resonance imaging (fMRI) studies has shown that amygdala responses to emotionally neutral pictures are exaggerated at a group level in patients with severe post-traumatic stress disorder (PTSD) [Hendler T, Rotshtein P, Yeshurun Y, Weizmann T, Kahn I, Ben-Bashat D, Malach R, Bleich A (2003) Neuroimage 19(3):587-600]. The present fMRI study tested the hypothesis that amygdala responses are elevated not only in response to negative pictures but also to neutral pictures as a function of disease severity in patients with mild symptoms and in subjects who did not develop symptoms. To this end, fMRI scans were performed in 10 patients with mild PTSD and 10 healthy controls (both victims of a bank robbery), during the execution of a visuo-attentional task in which they were asked to observe emotionally negative or neutral pictures. Control subjects showed enhanced amygdala responses to emotionally negative stimuli compared to neutral stimuli. On the contrary, PTSD patients were characterized by high amygdala responses to both neutral and emotional pictures, with no statistically significant difference between the two classes of stimuli. In the entire group, we found correlations among the severity of the PTSD symptoms, task performance, and amygdala activation during the processing of neutral stimuli. Results of this study suggest that amygdala responses and the selectivity of the emotional response to neutral stimuli are elevated as a function of disease severity in PTSD patients with mild symptoms.

Persistent genital arousal disorder associated with functional hyperconnectivity of an epileptic focus.

Persistent Genital Arousal Disorder (PGAD) refers to the experience of persistent sensations of genital arousal that are felt to be unprovoked, intrusive and unrelieved by one or several orgasms. It is often mistaken for hypersexuality since PGAD often results in a high frequency of sexual behaviour. At present little is known with certainty about the etiology of this condition. We described a woman with typical PGAD symptoms and orgasmic seizures that we found to be related to a specific epileptic focus. We performed a EEG/MEG and fMRI spontaneous activity study during genital arousal symptoms and after the chronic administration of 300 mg/day of topiramate. From MEG data an epileptic focus was localized in the left posterior insular gyrus (LPIG). FMRI data evidenced that sexual excitation symptoms with PGAD could be correlated with an increased functional connectivity (FC) between different brain areas: LPIG (epileptic focus), left middle frontal gyrus, left inferior and superior temporal gyrus and left inferior parietal lobe. The reduction of the FC observed after antiepileptic therapy was more marked in the left than in the right hemisphere in agreement with the lateralization identified by MEG results. Treatment completely abolished PGAD symptoms and functional hyperconnectivity. The functional hyperconnectivity found in the neuronal network including the epileptic focus could suggest a possible central mechanism for PGAD.

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.

An fMRI investigation on image generation in different sensory modalities: the influence of vividness.

In the present fMRI study the issue of the specific cortices activation during imagery generation in different sensory modalities is addressed. In particular, we tested whether the vividness variability of imagery was reflected in the BOLD signal within specific sensory cortices. Subjects were asked to generate a mental image for each auditory presented sentence. Each imagery modality was contrasted with an abstract sentence condition. In addition, subjects were asked to fill the Italian version of the Questionnaire Upon Mental Imagery (QMI) prior to each neuroimaging session. In general, greater involvement of sensory specific cortices in high-vivid versus low-vivid subjects was found for visual (occipital), gustatory (anterior insula), kinaesthetic (pre-motor), and tactile and for somatic (post-central parietal) imagery modalities. These results support the hypothesis that vividness is related to image format: high-vivid subjects would create more analogical representations relying on the same specific neural substrates active during perception with respect to low-vivid subjects. Results are also discussed according to the simulation perspective.