Uncover the Offensive Side of Disparagement Humor: An fMRI Study.

Disparagement humor is a kind of humor that denigrates, belittles an individual or a social group. In the aim to unveil the offensive side of these kinds of jokes, we have run an event-related fMRI study asking 30 healthy volunteers to judge the level of fun of a series of verbal stimuli that ended with a sentence that was socially inappropriate but funny (disparagement joke -DJ), socially inappropriate but not funny (SI) or neutral (N). Behavioral results showed disparagement jokes are perceived as funny and at the same time offensive. However, the level of offense in DJ is lower than that registered in SI stimuli. Functional data showed that DJ activated the insula, the SMA, the precuneus, the ACC, the dorsal striatum (the caudate nucleus), and the thalamus. These activations suggest that in DJ a feeling of mirth (and/or a desire to laugh) derived from the joke (e.g., SMA and precuneus) and the perception of the jokes' social inappropriateness (e.g., ACC and insula) coexist. Furthermore, DJ and SI share a common network related to mentalizing and to the processing of negative feelings, namely the medial prefrontal cortex, the putamen and the right thalamus.

Recovery from emotion recognition impairment after temporal lobectomy.

Mesial temporal lobe epilepsy (MTLE) can be associated with emotion recognition impairment that can be particularly severe in patients with early onset seizures (1-3). Whereas, there is growing evidence that memory and language can improve in seizure-free patients after anterior temporal lobectomy (ATL) (4), the effects of surgery on emotional processing are still unknown. We used functional magnetic resonance imaging (fMRI) to investigate short-term reorganization of networks engaged in facial emotion recognition in MTLE patients. Behavioral and fMRI data were collected from six patients before and after ATL. During the fMRI scan, patients were asked to make a gender decision on fearful and neutral faces. Behavioral data demonstrated that two patients with early onset right MTLE were impaired in fear recognition while fMRI results showed they lacked specific activations for fearful faces. Post-ATL behavioral data showed improved emotion recognition ability, while fMRI demonstrated the recruitment of a functional network for fearful face processing. Our results suggest that ATL elicited brain plasticity mechanisms allowing behavioral and fMRI improvement in emotion recognition.

Ranking brain areas encoding the perceived level of pain from fMRI data.

Pain perception is thought to emerge from the integrated activity of a distributed brain system, but the relative contribution of the different network nodes is still incompletely understood. In the present functional magnetic resonance imaging (fMRI) study, we aimed to identify the more relevant brain regions to explain the time profile of the perceived pain intensity in healthy volunteers, during noxious chemical stimulation (ascorbic acid injection) of the left hand. To this end, we performed multi-way partial least squares regression of fMRI data from twenty-two a-priori defined brain regions of interest (ROI) in each hemisphere, to build a model that could efficiently reproduce the psychophysical pain profiles in the same individuals; moreover, we applied a novel three-way extension of the variable importance in projection (VIP) method to summarize each ROI contribution to the model. Brain regions showing the highest VIP scores included the bilateral mid-cingulate, anterior and posterior insular, and parietal operculum cortices, the contralateral paracentral lobule, bilateral putamen and ipsilateral medial thalamus. Most of these regions, with the exception of medial thalamus, were also identified by a statistical analysis on mean ROI beta values estimated using the time course of the psychophysical rating as a regressor at the voxel level. Our results provide the first rank-ordering of brain regions involved in coding the perceived level of pain. These findings in a model of acute prolonged pain confirm and extend previous data, suggesting that a bilateral array of cortical areas and subcortical structures is involved in pain perception.

Human parietofrontal networks related to action observation detected at rest.

Recent data show a broad correspondence between human resting-state and task-related brain networks. We performed a functional magnetic resonance imaging (fMRI) study to compare, in the same subjects, the spatial independent component analysis (ICA) maps obtained at rest and during the observation of either reaching/grasping hand actions or matching static pictures. Two parietofrontal networks were identified by ICA from action observation task data. One network, specific to reaching/grasping observation, included portions of the anterior intraparietal cortex and of the dorsal and ventral lateral premotor cortices. A second network included more posterior portions of the parietal lobe, the dorsomedial frontal cortex, and more anterior and ventral parts, respectively, of the dorsal and ventral premotor cortices, extending toward Broca's area; this network was more generally related to the observation of hand action and static pictures. A good spatial correspondence was found between the 2 observation-related ICA maps and 2 ICA maps identified from resting-state data. The anatomical connectivity among the identified clusters was tested in the same volunteers, using persistent angular structure-MRI and deterministic tractography. These findings extend available knowledge of human parietofrontal circuits and further support the hypothesis of a persistent coherence within functionally relevant networks during rest.

An algorithm to estimate anatomical connectivity between brain regions using diffusion MRI.

The study of anatomical connectivity is essential for interpreting functional MRI data and for establishing how brain areas are linked together into networks to support higher-order functions. Diffusion-weighted MR images (DWI) and tractography provide a unique noninvasive tool to explore the connectional architecture of the brain. The identification of anatomical circuits associated with a specific function can be better accomplished by the joint application of diffusion and functional MRI. In this article, we propose a simple algorithm to identify the set of pathways between two regions of interest. The method is based upon running deterministic tractography from all possible starting positions in the brain and selecting trajectories that intersect both regions. We compare results from single-fiber tractography using diffusion tensor imaging and from multi-fiber tractography using reduced-encoding persistent angular structure (PAS) MRI on standard DWI datasets from healthy human volunteers. Our results show that, in comparison with single-fiber tractography, the multi-fiber technique reveals additional putative routes of connection. We demonstrate highly consistent results of the proposed technique over a cohort of 16 healthy subjects.

A regularization algorithm for decoding perceptual temporal profiles from fMRI data.

In several biomedical fields, researchers are faced with regression problems that can be stated as Statistical Learning problems. One example is given by decoding brain states from functional magnetic resonance imaging (fMRI) data. Recently, it has been shown that the general Statistical Learning problem can be restated as a linear inverse problem. Hence, new algorithms were proposed to solve this inverse problem in the context of Reproducing Kernel Hilbert Spaces. In this paper, we detail one iterative learning algorithm belonging to this class, called ν-method, and test its effectiveness in a between-subjects regression framework. Specifically, our goal was to predict the perceived pain intensity based on fMRI signals, during an experimental model of acute prolonged noxious stimulation. We found that, using a linear kernel, the psychophysical time profile was well reconstructed, while pain intensity was in some cases significantly over/underestimated. No substantial differences in terms of accuracy were found between the proposed approach and one of the state-of-the-art learning methods, the Support Vector Machines. Nonetheless, adopting the ν-method yielded a significant reduction in computational time, an advantage that became more evident when a relevant feature selection procedure was implemented. The ν-method can be easily extended and included in typical approaches for binary or multiple classification problems, and therefore it seems well-suited to build effective brain activity estimators.

Neural substrates for observing and imagining non-object-directed actions.

The present fMRI study was aimed at assessing the cortical areas active when individuals observe non-object-directed actions (mimed, symbolic, and meaningless), and when they imagine performing those same actions. fMRI signal increases in common between action observation and motor imagery were found in the premotor cortex and in a large region of the inferior parietal lobule. While the premotor cortex activation overlapped that previously found during the observation and imagination of object-directed actions, in the parietal lobe the signal increase was not restricted to the intraparietal sulcus region, known to be active during the observation and imagination of object-directed actions, but extended into the supramarginal and angular gyri. When contrasting motor imagery with the observation of non-object-directed actions, signal increases were found in the mesial frontal and cingulate cortices, the supramarginal gyrus, and the inferior frontal gyrus. The opposite contrast showed activation virtually limited to visual areas. In conclusion, the present data define the common circuit for observing and imagining non-object-directed actions. In addition, they show that the representation of non-object-directed actions include parietal regions not found to be involved in coding object-directed actions.

Processing the socially relevant parts of faces.

Faces are processed by a distributed neural system in the visual as well as in the non-visual cortex [the "core" and the "extended" systems, J.V. Haxby, E.A. Hoffman, M.I. Gobbini, The distributed human neural system for face perception, Trends Cogn. Sci. 4 (2000) 223-233]. Yet, the functions of the different brain regions included in the face processing system are far from clear. On the basis of the case study of a patient unable to recognize fearful faces, Adolphs et al. [R. Adolphs, F. Gosselin, T.W. Buchanan, D. Tranel, P. Schyns, A.R. Damasio, A mechanism for impaired fear recognition after amygdala damage, Nature 433 (2005) 68-72] suggested that the amygdala might play a role in orienting attention towards the eyes, i.e. towards the region of face conveying most information about fear. In a functional magnetic resonance (fMRI) study comparing patterns of activation during observation of whole faces and parts of faces displaying neutral expressions, we evaluated the neural systems for face processing when only partial information is provided, as well as those involved in processing two socially relevant facial areas (the eyes and the mouth). Twenty-four subjects were asked to perform a gender decision task on pictures showing whole faces, upper faces (eyes and eyebrows), and lower faces (mouth). Our results showed that the amygdala was activated more in response to the whole faces than to parts of faces, indicating that the amygdala is involved in orienting attention toward eye and mouth. Processing of parts of faces in isolation was found to activate other regions within both the "core" and the "extended" systems, as well as structures outside this network, thus suggesting that these structures are involved in building up the representation of the whole face from its parts.

Multimodal MRI in the characterization of glial neoplasms: the combined role of single-voxel MR spectroscopy, diffusion imaging and echo-planar perfusion imaging.

INTRODUCTION: Diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and MR spectroscopy (MRS) provide useful data for tumor evaluation. To assess the contribution of these multimodal techniques in grading glial neoplasms, we compared the value of DWI, PWI and MRS in the evaluation of histologically proven high- and low-grade gliomas in a population of 105 patients. METHODS: Independently for each modality, the following variables were used to compare the tumors: minimum apparent diffusion coefficient (ADC) and maximum relative cerebral blood volume (rCBV) normalized values between tumor and healthy tissue, maximum Cho/Cr ratio and minimum NAA/Cr ratio in tumor, and scored lactate and lipid values in tumor. The Mann-Whitney and Wilcoxon tests were employed to compare DWI, PWI and MRS between tumor types. Logistic regression analysis was used to determine which parameters best increased the diagnostic accuracy in terms of sensitivity, specificity, and positive and negative predictive values. ROC curves were determined for parameters with high sensitivity and specificity to identify threshold values to separate high- from low-grade lesions. RESULTS: Statistically significant differences were found for rCBV tumor/normal tissue ratio, and NAA/Cr ratio in tumor and Cho/Cr ratio in tumor between low- and high-grade tumors. The best performing single parameter for group classification was the normalized rCBV value; including all parameters, statistical significance was reached by rCBV tumor/normal tissue ratio, NAA/Cr tumor ratio and lactate. From the ROC curves, a high probability for a neoplasm to be a high-grade lesion was associated with a rCBV tumor/normal tissue ratio of >1.16 and NAA/Cr tumor ratio of <0.44. CONCLUSION: Combining PWI and MRS with conventional MR imaging increases the accuracy of the attribution of malignancy to glial neoplasms. The best performing parameter was found to be the perfusion level.

An ARX model-based approach to trial by trial identification of fMRI-BOLD responses.

Being able to estimate the fMRI-BOLD response following a single task or stimulus is certainly of value, since it allows to characterize its relationship to different aspects either of the stimulus, or of the subject's performance. In order to detect and characterize BOLD responses in single trials, we developed and validated a procedure based on an AutoRegressive model with eXogenous Input (ARX). The use of an individual exogenous input for each voxel makes the modeling sensitive enough to reveal differences across regions, avoiding any a priori assumption about the reference signal. The detection of variability across trials is ensured by a suitable choice, for each voxel, of the order of the moving average, which in our implementation determines the relative delay between the recorded and the reference signal. This is a quality useful in finding different time profiles of activation from high temporal resolution fMRI data. The results obtained from simulated fMRI data resulting from synthetic activations in actual noise indicate that such approach allows to evaluate important features of the response, such as the time to onset, and time to peak. Moreover, the results obtained from real high temporal resolution fMRI data acquired at l.5 T during a motor task are consistent with previous knowledge about the responses of different cortical areas in motor programming and execution. The proposed procedure should also prove useful as a pre-processing step in different approaches to the analysis of fMRI data.

Humor comprehension and appreciation: an FMRI study.

Humor is a unique ability in human beings. Suls [A two-stage model for the appreciation of jokes and cartoons. In P. E. Goldstein & J. H. McGhee (Eds.), The psychology of humour. Theoretical perspectives and empirical issues. New York: Academic Press, 1972, pp. 81-100] proposed a two-stage model of humor: detection and resolution of incongruity. Incongruity is generated when a prediction is not confirmed in the final part of a story. To comprehend humor, it is necessary to revisit the story, transforming an incongruous situation into a funny, congruous one. Patient and neuroimaging studies carried out until now lead to different outcomes. In particular, patient studies found that right brain-lesion patients have difficulties in humor comprehension, whereas neuroimaging studies suggested a major involvement of the left hemisphere in both humor detection and comprehension. To prevent activation of the left hemisphere due to language processing, we devised a nonverbal task comprising cartoon pairs. Our findings demonstrate activation of both the left and the right hemispheres when comparing funny versus nonfunny cartoons. In particular, we found activation of the right inferior frontal gyrus (BA 47), the left superior temporal gyrus (BA 38), the left middle temporal gyrus (BA 21), and the left cerebellum. These areas were also activated in a nonverbal task exploring attribution of intention [Brunet, E., Sarfati, Y., Hardy-Bayle, M. C., & Decety, J. A PET investigation of the attribution of intentions with a nonverbal task. Neuroimage, 11, 157-166, 2000]. We hypothesize that the resolution of incongruity might occur through a process of intention attribution. We also asked subjects to rate the funniness of each cartoon pair. A parametric analysis showed that the left amygdala was activated in relation to subjective amusement. We hypothesize that the amygdala plays a key role in giving humor an emotional dimension.

Impaired fear processing in right mesial temporal sclerosis: a fMRI study.

Lesion and neuroimaging studies have demonstrated that the mesial temporal lobe is crucial for recognizing emotions from facial expressions. In humans, bilateral amygdala damage is followed by impaired recognition of facial expressions of fear. To evaluate the influence of unilateral mesial temporal lobe damage we examined recognition of facial expressions and functional magnetic resonance (fMRI) brain activation associated with incidental processing of fearful faces in thirteen mesial temporal lobe epilepsy (MTLE) patients (eight with right MTLE, five with left MTLE). We also examined the effect of early versus later damage, comparing subjects with hippocampal-amygdalar sclerosis (MTS) and seizures occurring before five years of age to epilepsy patients with late onset seizures. Fourteen healthy volunteers participated as controls. Neuropsychological testing demonstrated that the ability of right MTLE patients to recognize fearful facial expressions is impaired. Patients with early onset of seizures were the most severely impaired. This deficit was associated with defective activation of a neural network involved in the processing of fearful expressions, which in controls and left MTLE included the left inferior frontal cortex and several occipito-temporal structures of both hemispheres.

Percept-related activity in the human somatosensory system: functional magnetic resonance imaging studies.

In this paper, we review blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies addressing the neural correlates of touch, thermosensation, pain and the mechanisms of their cognitive modulation in healthy human subjects. There is evidence that fMRI signal changes can be elicited in the parietal cortex by stimulation of single mechanoceptive afferent fibers at suprathreshold intensities for conscious perception. Positive linear relationships between the amplitude or the spatial extents of BOLD fMRI signal changes, stimulus intensity and the perceived touch or pain intensity have been described in different brain areas. Some recent fMRI studies addressed the role of cortical areas in somatosensory perception by comparing the time course of cortical activity evoked by different kinds of stimuli with the temporal features of touch, heat or pain perception. Moreover, parametric single-trial functional MRI designs have been adopted in order to disentangle subprocesses within the nociceptive system. Available evidence suggest that studies that combine fMRI with psychophysical methods may provide a valuable approach for understanding complex perceptual mechanisms and top-down modulation of the somatosensory system by cognitive factors specifically related to selective attention and to anticipation. The brain networks underlying somatosensory perception are complex and highly distributed. A deeper understanding of perceptual-related brain mechanisms therefore requires new approaches suited to investigate the spatial and temporal dynamics of activation in different brain regions and their functional interaction.

Functional activity mapping of the mesial hemispheric wall during anticipation of pain.

The relative contributions of autonomic arousal and of cognitive processing to cortical activity during anticipation of pain, and the role of changes in thalamic outflow, are still largely unknown. To address these issues, we investigated with functional magnetic resonance imaging (fMRI) the activity of the contralateral mesial hemispheric wall in 56 healthy volunteers while they expected the stimulation of one foot, which could be either painful or innocuous. The waiting period was characterized by emotional arousal, a moderate rise in heart rate, and by increases in mean fMRI signals in the medial thalamus, mid- and posterior cingulate cortex, and in the putative foot area of the primary somatosensory and motor cortex. The same brain regions, excepting posterior cingulate, were also activated by somatosensory stimulation. We identified by cross-correlation analysis a cluster population whose fMRI signal time course was related to the mean heart rate (HR) profile, showing selective changes of activity during the waiting period. Positively correlated clusters were found mainly in sensorimotor areas, mid- and posterior cingulate, and dorsomedial prefrontal cortex. Negatively correlated clusters predominated in the perigenual anterior cingulate and ventromedial prefrontal cortex. HR clusters had different characteristics from, and showed limited spatial overlap with, clusters whose fMRI signals were related to the psychophysical pain intensity profile; however, both cluster populations were affected by anticipation. These findings unravel a complex pattern of brain activity during uncertain anticipation of noxious input, likely related both to changes in the level of arousal and to cognitive modulation of the pain system.

Independent time courses of supraspinal nociceptive activity and spinally mediated behavior during tonic pain.

The behavioral response to acute tissue injury is usually characterized by different phases, but the brain mechanisms underlying changes in pain-related behavior over time are still poorly understood. We aimed to analyze time-dependent changes in metabolic activity levels of 49 forebrain structures in the formalin pain model, using the autoradiographic 2-deoxyglucose method in unanesthetized, freely moving rats. We examined rats during the first phase of pain-related reactions ('early' groups), or during the third recovery phase, 60 min later, when the supraspinally mediated behavioral responses were reduced ('late' group). In the early groups, metabolic rates were bilaterally increased over control values in the periaqueductal gray, zona incerta and in several thalamic nuclei (anteroventral, centrolateral, lateral dorsal, parafascicular, posteromedial, submedius, ventromedial, and ventrobasal complex), as well as in the habenulae and in the parietal, cingulate, antero-dorsal insular, and anterior piriform cortex. A contralateral, somatotopically specific activation was found in the putative hindlimb representation area of the somatosensory cortex. In the late group, noxious-induced activation declined in most structures. However, metabolic rates were higher than controls in the periaqueductal gray and zona incerta and in two other structures not previously active: the prerubral area/field of Forel and the arcuate hypothalamic nucleus. These findings provide a time-dependent functional map of nociceptive and anti-nociceptive forebrain circuits during tonic pain. The parallel decrease in licking behavior and forebrain activity, at times when spinally mediated limb flexion responses were still present, suggests that endogenous antinociceptive systems may differently modulate spinal and supraspinal nociceptive networks following acute tissue injury.

Does anticipation of pain affect cortical nociceptive systems?

Anticipation of pain is a complex state that may influence the perception of subsequent noxious stimuli. We used functional magnetic resonance imaging (fMRI) to study changes of activity of cortical nociceptive networks in healthy volunteers while they expected the somatosensory stimulation of one foot, which might be painful (subcutaneous injection of ascorbic acid) or not. Subjects had no previous experience of the noxious stimulus. Mean fMRI signal intensity increased over baseline values during anticipation and during actual stimulation in the putative foot representation area of the contralateral primary somatosensory cortex (SI). Mean fMRI signals decreased during anticipation in other portions of the contralateral and ipsilateral SI, as well as in the anteroventral cingulate cortex. The activity of cortical clusters whose signal time courses showed positive or negative correlations with the individual psychophysical pain intensity curve was also significantly affected during the waiting period. Positively correlated clusters were found in the contralateral SI and bilaterally in the anterior cingulate, anterior insula, and medial prefrontal cortex. Negatively correlated clusters were found in the anteroventral cingulate bilaterally. In all of these areas, changes during anticipation were of the same sign as those observed during pain but less intense ( approximately 30-40% as large as peak changes during actual noxious stimulation). These results provide evidence for top-down mechanisms, triggered by anticipation, modulating cortical systems involved in sensory and affective components of pain even in the absence of actual noxious input and suggest that the activity of cortical nociceptive networks may be directly influenced by cognitive factors.

Human brain language processing areas identified by functional magnetic resonance imaging using a lexical decision task.

The purpose of this study was to validate a functional magnetic resonance imaging (fMRI) paradigm to activate both anterior and posterior language areas while collecting accuracy and reaction time data on subjects' performance. The paradigm was based on alternating graphemic and lexical decision tasks. In line with the classical model of language organisation, based on lesion data, and with the results of previous neuroimaging studies, cortical activation associated with lexical decision-making was strongly lateralised to the left hemisphere and involved a network of regions in the frontal, temporal and parietal lobes. Single subject analysis demonstrated that the activation paradigm we propose is suitable for detecting language processing areas in humans for clinical studies.

'Mirror pain' in the formalin test: behavioral and 2-deoxyglucose studies.

Subcutaneous injection of a dilute formaldehyde solution (5 or 10%) into a hind paw induced, in the majority of rats, the appearance of 'mirror pain': licking the contralateral untreated hind paw 10-60 min after injection. Contralateral licking activity was much less frequent than the ipsilaterally directed one, but the overall intensities of the two responses were positively correlated. Qualitatively, the two behaviours were similar. Functional activity levels of the lumbar spinal cord, as revealed by the 2-deoxyglucose (2-DG) technique, were increased bilaterally over the first hour after unilateral hind limb formalin injection in unanesthetized, freely moving rats. The enhancement of the [14C]2-DG uptake could be detected both in dorsal and ventral horns, as well as in the gray matter surrounding the central canal, and the anterolateral and dorsolateral funiculi. These metabolic changes may reflect an enhancement of the functional activity of both interneuronal pools and units projecting to supraspinal centers, giving rise to a referred contralateral pain.