Massimo Caulo

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.

Human brain activation during passive listening to sounds from different locations: An fMRI and MEG study

Recent animal and human studies indicate the existence of a neural pathway for sound localization, which is similar to the “where” pathway of the visual system and distinct from the sound identification pathway. This study sought to highlight this pathway using a passive listening protocol. We employed fMRI to study cortical areas, activated during the processing of sounds coming from different locations, and MEG to disclose the temporal dynamics of these areas. In addition, the hypothesis of different activation levels in the right and in the left hemispheres, due to hemispheric specialization of the human brain, was investigated. The fMRI results indicate that the processing of sound, coming from different locations, activates a complex neuronal circuit, similar to the sound localization system described in monkeys known as the auditory “where” pathway. This system includes Heschls gyrus, the superior temporal gyrus, the supramarginal gyrus, and the inferior and middle frontal lobe. The MEG analysis allowed assessment of the timing of this circuit: the activation of Heschls gyrus was observed 139 ms after the auditory stimulus, the peak latency of the source located in the superior temporal gyrus was at 156 ms, and the inferior parietal lobule and the supramarginal gyrus peaked at 162 ms. Both hemispheres were found to be involved in the processing of sounds coming from different locations, but a stronger activation was observed in the right hemisphere. Hum. Brain Mapping, 2005.

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.

Seizure-induced brain lesions: a wide spectrum of variably reversible MRI abnormalities.

Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p=0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p=0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention.

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.

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.

Noxious somatosensory stimulation affects the default mode of brain function: evidence from functional MR imaging.

PURPOSE To investigate whether default mode network (DMN) spatial properties can be directly affected by pain, with a comparison of painful and nonpainful conditions. MATERIALS AND METHODS The authors performed a functional magnetic resonance (MR) imaging study, approved by the local institutional ethics committee, involving 10 healthy male subjects (age range, 18-45 years) who gave written informed consent. The subjects underwent two experimental sessions of median nerve electrical stimulation at painful and nonpainful levels. Independent component analysis of the functional MR imaging data was performed to determine the DMN spatiotemporal pattern. Group-level DMN connectivity maps for painful and nonpainful conditions were obtained (P < .001, corrected with false discovery rate). The contrast between the connectivity maps in the two conditions was also computed (P < .05, corrected with false discovery rate). RESULTS The DMN maintained its typical temporal properties but was subject to modifications in connectivity pattern during painful stimulation, affecting the brain areas associated with pain processing. Increased connectivity in painful conditions was found mainly in the left prefrontal cortex and posterior cingulate cortex-precuneus, and decreased connectivity was found in the lateral parietal cortex. CONCLUSION Study findings were in line with the impairments of the DMN reported in patients with chronic pain. They support the hypothesis that alteration of the DMN connectivity pattern localized in specific brain areas during acute pain, if repeated across time, might induce permanent changes that could disrupt the DMN functional architecture.

Somatotopy of anterior cingulate cortex (ACC) and supplementary motor area (SMA) for electric stimulation of the median and tibial nerves: An fMRI study

In this study, we tested whether there is a somatotopic sensory organization in human anterior cingulate cortex (ACC) and supplementary motor area (SMA), as a reflection of central feed-back sensory processing for motor control. To this aim, fMRI recordings were performed in 15 normal young adults during nonpainful and painful electric stimulation of median nerve at the wrist and tibial nerve at the medial malleolus. Results showed that the representation of median nerve area was more anterior in the ACC and more inferior in the SMA than the one of tibial nerve area. This was true for both nonpainful and painful stimulation intensities. These results point to a somatotopic sensory organization of human ACC and SMA.

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.

Audio-visual crossmodal interactions in environmental perception: an fMRI investigation

In everyday life, the perception of surrounding events rarely takes place through a single sensory modality. Rather, perception is the result of the processing of information converging from the different senses. Behavioural research often proposes that the binding of different kinds of sensory input creates advantages in the detection, localization, and recognition of external events (King and Calvert 2001). However, the modalities with which multiple sensory cues deriving from the same object merge to form a coherent precept still represent a controversial topic in literature. Research in this field, from the animal studies of Stein and Meredith (1993) to the latest human neuroimaging investigations (for a review see Calvert 2001), has shown the importance of the temporal and spatial congruence of incoming stimuli in establishing crossmodal associations. Nevertheless, other characteristics, like semantic congruence, play a significant role in binding crossmodal associations, especially during the integration of information about complex objects. Thus the analysis of the semantic relationships established in crossmodal stimulation may be a promising instrument for exploring the neural substrates of multi-sensory integration. At least two main theoretical views on the neural pathways involved in crossmodal processing have been proposed: the first one stresses the importance of multisensory cortical areas that receive projections from the different senses (Calvert 2001); the second view emphasizes the importance of the combined activity of the modality-specific cortices by means of synchronized firing (Ettlinger and Wilson 1990). At the same time, an effort has been made to identify regions of the human brain, called heteromodal cortices, that receive afferents from different senses and are analogous to those described in animals. At the cortical level, these regions have been found in the superior temporal sulcus, in the intraparietal sulcus, and in the prefrontal and limbic cortices (Mesulam 1998; Calvert 2001). Heteromodal areas have also been found in subcortical structures, such as the superior colliculus (Stein and Meredith 1993). Recent neuroimaging investigations attempted to establish a relationship between different crossmodal tasks and the activation of specific heteromodal areas (Calvert 2001). Experimental evidence reported the activation of the lateral temporal cortex in response to the integration of audio-visual information during recognition or identification tasks, as described by Calvert et al. (2000). These authors investigated the regions that exhibited supraadditive response enhancement to congruent audiovisual speech using functional magnetic resonance imaging (fMRI). They observed strong interaction effects in the left superior temporal sulcus. Recently, Beauchamp et al. (2004) investigated the contribution of the superior temporal areas in the integration of visual and auditory information about Cogn Process (2004) 5: 167–174 DOI 10.1007/s10339-004-0024-0