Antonio Ferretti

Dynamics of male sexual arousal: distinct components of brain activation revealed by fMRI

The peripheral mechanisms of male sexual arousal are well known. Recently, neuroimaging techniques, such as PET or fMRI, allowed the investigation of the subjacent cerebral mechanisms. In ten healthy subjects, we have simultaneously recorded fMRI images of brain activation elicited by viewing erotic scenes, and the time course of penile tumescence by means of a custom-built MRI-compatible pneumatic cuff. We have compared activation elicited by video clips with a long duration, that led to sexual arousal and penile erection, and activation elicited by briefly presented still images, that did induce sexual arousal without erection. This comparison and the use of the time course of penile tumescence in video clips allowed to perform a time resolved data analysis and to correlate different patterns of brain activation with different phases of sexual response. The activation maps highlighted a complex neural circuit involved in sexual arousal. Of this circuit, only a few areas (anterior cingulate, insula, amygdala, hypothalamus, and secondary somatosensory cortices) were specifically correlated with penile erection. Finally, these areas showed distinct dynamic relationships with the time course of sexual response. These differences might correspond to different roles in the development and appraisal of the sexual response. These findings shed light on the psychophysiology of male sexuality and open new perspectives for the diagnosis, therapy, and possible rehabilitation of sexual dysfunction.

The sense of touch: Embodied simulation in a visuotactile mirroring mechanism for observed animate or inanimate touch

Previous studies have shown a shared neural circuitry in the somatosensory cortices for the experience of ones own body being touched and the sight of intentional touch. Using functional magnetic resonance imaging (fMRI), the present study aimed to elucidate whether the activation of a visuotactile mirroring mechanism during touch observation applies to the sight of any touch, that is, whether it is independent of the intentionality of observed touching agent. During fMRI scanning, healthy participants viewed video clips depicting a touch that was intentional or accidental, and occurring between animate or inanimate objects. Analyses showed equal overlapping activation for all the touch observation conditions and the experience of ones own body being touched in the bilateral secondary somatosensory cortex (SII), left inferior parietal lobule (IPL)/supramarginal gyrus, bilateral temporal-occipital junction, and left precentral gyrus. A significant difference between the sight of an intentional touch, compared to an accidental touch, was found in the left primary somatosensory cortex (SI/Brodmanns area [BA] 2). Interestingly, activation in SI/BA 2 significantly correlated with the degree of intentionality of the observed touch stimuli as rated by participants. Our findings show that activation of a visuotactile mirroring mechanism for touch observation might underpin an abstract notion of touch, whereas activation in SI might reflect a human tendency to resonate more with a present or assumed intentional touching agent.

Neural correlates of focused attention and cognitive monitoring in meditation.

Meditation refers to a family of complex emotional and attentional regulatory practices, which can be classified into two main styles - focused attention (FA) and open monitoring (OM) - involving different attentional, cognitive monitoring and awareness processes. In a functional magnetic resonance study we originally characterized and contrasted FA and OM meditation forms within the same experiment, by an integrated FA-OM design. Theravada Buddhist monks, expert in both FA and OM meditation forms, and lay novices with 10 days of meditation practice, participated in the experiment. Our evidence suggests that expert meditators control cognitive engagement in conscious processing of sensory-related, thought and emotion contents, by massive self-regulation of fronto-parietal and insular areas in the left hemisphere, in a meditation state-dependent fashion. We also found that anterior cingulate and dorsolateral prefrontal cortices play antagonist roles in the executive control of the attention setting in meditation tasks. Our findings resolve the controversy between the hypothesis that meditative states are associated to transient hypofrontality or deactivation of executive brain areas, and evidence about the activation of executive brain areas in meditation. Finally, our study suggests that a functional reorganization of brain activity patterns for focused attention and cognitive monitoring takes place with mental practice, and that meditation-related neuroplasticity is crucially associated to a functional reorganization of activity patterns in prefrontal cortex and in the insula.

Somato-motor inhibitory processing in humans: An event-related functional MRI study

Inhibiting inappropriate behavior and thoughts is an essential ability for humans, but the regions responsible for inhibitory processing are a matter of continuous debate. This is the first study of somatosensory go/nogo tasks using event-related functional magnetic resonance imaging (fMRI). Fifteen subjects preformed two different types of go/nogo task, i.e. (1) Movement and (2) Count, to compare with previous studies using visual go/nogo tasks, and confirm whether the inhibitory processing is dependent on sensory modalities. Go and nogo stimuli were presented with an even probability. Our data indicated that the response inhibition network involved the dorsolateral (DLPFC) and ventrolateral (VLPFC) prefrontal cortices, pre-supplementary motor area (pre-SMA), anterior cingulate cortex (ACC), inferior parietal lobule (IPL), insula, and temporoparietal junction (TPJ), which were consistent with previous results obtained using visual go/nogo tasks. These activities existed in both Movement and Count Nogo trials. Therefore, our results suggest that the network for inhibitory processing is not dependent on sensory modalities but reflects common neural activities. In addition, there were differences of activation intensity between Movement and Count Nogo trials in the prefrontal cortex, temporal lobe, and ACC. Thus, inhibitory processing would involve two neural networks, common and uncommon regions, depending on the required response mode.

Functional topography of the secondary somatosensory cortex for nonpainful and painful stimuli: an fMRI study

The regional activity of the contralateral primary (SI) and the bilateral secondary (SII) somatosensory areas during median nerve stimulations at five intensity levels (ranging from nonpainful motor threshold to moderate pain) was studied by means of functional magnetic resonance imaging (fMRI). The aim was to characterize the functional topography of SII compared to SI as a function of the stimulus intensity. Results showed that the galvanic stimulation of the median nerve activated the contralateral SI at all stimulus intensities. When considered as a single region, SII was more strongly activated in the contralateral than in the ipsilateral hemisphere. When a finer spatial analysis of the SII responses was performed, the activity for the painful stimulation was localized more posteriorly compared to that for the nonpainful stimulation. This is the first report on such a SII segregation for transient galvanic stimulations. The activity (relative signal intensity) of this posterior area increased with the increase of the stimulus intensity. These results suggest a spatial segregation of the neural populations that process signals conveyed by dorsal column-medial lemniscus (nonpainful signals) and neospinothalamic (painful signals) pathways. Further fMRI experiments should evaluate the functional properties of these two SII subregions during tasks involving sensorimotor integration, learning, and memory demands.

Topographic organization of the human primary and secondary somatosensory cortices: comparison of fMRI and MEG findings

We studied MEG and fMRI responses to electric median and tibial nerve stimulation in five healthy volunteers. The aim was to compare the results with those of a previous study using only fMRI on the primary and secondary somatosensory cortices in which the somatotopic organization of SII was observed with fMRI. In the present work we focus on the comparison between fMRI activation and MEG equivalent current dipole (ECD) localizations in the SII area. The somatotopic organization of SII was confirmed by MEG, with the upper limb areas located more anteriorly and more inferiorly than the lower limb areas. In addition a substantial consistency of the ECD locations with the areas of fMRI activation was observed, with an average mismatch of about 1 cm. MEG ECDs and fMRI activation areas showed comparable differences in SI.

Chapter 5 Fundamentals of Electroencefalography, Magnetoencefalography, and Functional Magnetic Resonance Imaging

This review introduces readers to fundamentals of electroencephalography (EEG), magnetoencephalography (MEG), and functional magnetic resonance imaging (fMRI). EEG and MEG signals are mainly produced by postsynaptic ionic currents of synchronically active pyramidal cortical neurons. These signals reflect the integrative information processing of neurons representing the output of cortical neural modules. EEG and MEG signals have a high temporal resolution (<1ms) ideal to investigate an emerging propriety of brain physiology, namely the brain rhythms. A background spontaneous oscillatory activity of brain neurons at about 10Hz generates dominant alpha rhythms of resting-state EEG and MEG activity. This background activity is blocked during sensory and cognitive-motor events. Standard EEG shows a low spatial resolution (5-9cm), which partially improves by high-resolution EEG including 64-128 channels and source estimation techniques (1-3cm); source estimation of MEG data shows a better spatial resolution (0.5-2cm). fMRI is an indirect measurement of regional brain activity based on the ratio between deoxyhemoglobin and oxyhemoglobin blood (BOLD) during events referenced to baseline conditions. Event-related BOLD response has low temporal resolution (>1s) and quite high spatial resolution (<1cm), and is especially suitable to investigate spatial details of both cortical and subcortical activation.

Human secondary somatosensory cortex is involved in the processing of somatosensory rare stimuli: An fMRI study

In the human somatosensory system, the contralateral primary somatosensory cortex (SI) is presumed to process and encode type and intensity of the sensory inputs, whereas the bilateral secondary somatosensory cortex (SII) is believed to perform higher order functions including sensorimotor integration, integration of information from the two body halves, attention, learning and memory. In this fMRI study we investigated the effect of attention on the activation of SI and SII, as induced by nonpainful and painful rare deviant electric stimuli during somatosensory oddball tasks. The working hypothesis is of stronger effects of attention on SII with respect to SI. Four runs were acquired according to an oddball scheme. Frequent nonpainful electrical stimuli were delivered to the ulnar nerve at motor threshold, whereas rare/deviant stimuli were delivered to median nerve in four conditions (one condition per run): nonpainful, painful, counting nonpainful, and counting painful. Results showed a statistically significant fMRI activation in bilateral SII but not in contralateral SI when the rare/deviant median nerve stimuli were delivered at nonpainful and painful levels as well as at the two levels of attention considered (i.e., associated with counting and non-counting tasks). Furthermore, fMRI activation in SII did not differ across the different levels of stimulus intensity (nonpainful, painful) and attention (non-counting, counting). These results corroborate the notion that SII is the target of independent pathways for the processing and integration of nonpainful and painful somatosensory stimuli salient for further high-order elaborations.

Topographic organization of the human primary and secondary somatosensory areas: an fMRI study.

The topographical organization of SI and SII somatosensory areas was investigated using fMRI at 1.5 T and electrical sensory stimulation. Electrical stimuli were delivered unilaterally to the median nerve at the wrist and to the tibial nerve at the medial malleolus, during a block paradigm study. In all subjects, activation was observed, contralaterally to the stimulated side, in the post-central gyrus, in the posterior parietal cortex, in the mesial pre-frontal region and, bilaterally, in the supratemporal region at the level of the Sylvian fissure. The latter region, corresponding presumably to SII, showed a rough but clearcut topographical organization, with the median nerve areas located more posteriorly. In addition, weaker activations were observed in some subjects in the ipsilateral mesial prefrontal region and in the ipsilateral posterior parietal cortex. Information contained in the present study represent an interesting database for future investigations on the effects of sensorimotor learning in normal individuals on plastic reorganization following a lesion of the primary sensorimotor centers, i.e. in stroke patients, on the topography and balance between upper and lower limb representations in primary and secondary somatosensory cortices.

Multisite longitudinal reliability of tract-based spatial statistics in diffusion tensor imaging of healthy elderly subjects

Large-scale longitudinal neuroimaging studies with diffusion imaging techniques are necessary to test and validate models of white matter neurophysiological processes that change in time, both in healthy and diseased brains. The predictive power of such longitudinal models will always be limited by the reproducibility of repeated measures acquired during different sessions. At present, there is limited quantitative knowledge about the across-session reproducibility of standard diffusion metrics in 3T multi-centric studies on subjects in stable conditions, in particular when using tract based spatial statistics and with elderly people. In this study we implemented a multi-site brain diffusion protocol in 10 clinical 3T MRI sites distributed across 4 countries in Europe (Italy, Germany, France and Greece) using vendor provided sequences from Siemens (Allegra, Trio Tim, Verio, Skyra, Biograph mMR), Philips (Achieva) and GE (HDxt) scanners. We acquired DTI data (2 × 2 × 2 mm(3), b = 700 s/mm(2), 5 b0 and 30 diffusion weighted volumes) of a group of healthy stable elderly subjects (5 subjects per site) in two separate sessions at least a week apart. For each subject and session four scalar diffusion metrics were considered: fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial (AD) diffusivity. The diffusion metrics from multiple subjects and sessions at each site were aligned to their common white matter skeleton using tract-based spatial statistics. The reproducibility at each MRI site was examined by looking at group averages of absolute changes relative to the mean (%) on various parameters: i) reproducibility of the signal-to-noise ratio (SNR) of the b0 images in centrum semiovale, ii) full brain test-retest differences of the diffusion metric maps on the white matter skeleton, iii) reproducibility of the diffusion metrics on atlas-based white matter ROIs on the white matter skeleton. Despite the differences of MRI scanner configurations across sites (vendors, models, RF coils and acquisition sequences) we found good and consistent test-retest reproducibility. White matter b0 SNR reproducibility was on average 7 ± 1% with no significant MRI site effects. Whole brain analysis resulted in no significant test-retest differences at any of the sites with any of the DTI metrics. The atlas-based ROI analysis showed that the mean reproducibility errors largely remained in the 2-4% range for FA and AD and 2-6% for MD and RD, averaged across ROIs. Our results show reproducibility values comparable to those reported in studies using a smaller number of MRI scanners, slightly different DTI protocols and mostly younger populations. We therefore show that the acquisition and analysis protocols used are appropriate for multi-site experimental scenarios.