Central Somatosensory Networks Respond to a De Novo Innervated Penis: A Proof of Concept in Three Spina Bifida Patients.

INTRODUCTION: Spina bifida (SB) causes low spinal lesions, and patients often have absent genital sensation and a highly impaired sex life. TOMAX (TO MAX-imize sensation, sexuality and quality of life) is a surgical procedure whereby the penis is newly innervated using a sensory nerve originally targeting the inguinal area. Most TOMAX-treated SB patients initially experience penile stimulation as inguinal sensation, but eventually, the perception shifts to penis sensation with erotic feelings. The brain mechanisms mediating this perceptual shift, which are completely unknown, could hold relevance for understanding the brain's role in sexual development. AIM: The aim of this study was to study how a newly perceived penis would be mapped onto the brain after a lifelong disconnection. METHODS: Three TOMAX-treated SB patients participated in a functional magnetic resonance imagery experiment while glans penis, inguinal area, and index finger were stimulated with a paint brush. MAIN OUTCOME MEASURE: Brush stimulation-induced activation of the primary somatosensory cortex (SI) and functional connectivity between SI and remote cerebral regions. RESULTS: Stimulation of the re-innervated side of the glans penis and the intact contralateral inguinal area activated a very similar location on SI. Yet, connectivity analysis identified distinct SI functional networks. In all three subjects, the middle cingulate cortex (MCC) and the parietal operculum-insular cortex (OIC) were functionally connected to SI activity during glans penis stimulation, but not to SI activity induced by inguinal stimulation. CONCLUSIONS: Investigating central somatosensory network activity to a de novo innervated penis in SB patients is feasible and informative. The consistent involvement of MCC and OIC above and beyond the brain network expected on the basis of inguinal stimulation suggests that these areas mediate the novel penis sensation in these patients. The potential role of MCC and OIC in this process is discussed, along with recommendations for further research.

Inter-individual differences in audio-motor learning of piano melodies and white matter fiber tract architecture.

Humans vary substantially in their ability to learn new motor skills. Here, we examined inter-individual differences in learning to play the piano, with the goal of identifying relations to structural properties of white matter fiber tracts relevant to audio-motor learning. Non-musicians (n = 18) learned to perform three short melodies on a piano keyboard in a pure audio-motor training condition (vision of their own fingers was occluded). Initial learning times ranged from 17 to 120 min (mean ± SD: 62 ± 29 min). Diffusion-weighted magnetic resonance imaging was used to derive the fractional anisotropy (FA), an index of white matter microstructural arrangement. A correlation analysis revealed that higher FA values were associated with faster learning of piano melodies. These effects were observed in the bilateral corticospinal tracts, bundles of axons relevant for the execution of voluntary movements, and the right superior longitudinal fasciculus, a tract important for audio-motor transformations. These results suggest that the speed with which novel complex audio-motor skills can be acquired may be determined by variability in structural properties of white matter fiber tracts connecting brain areas functionally relevant for audio-motor learning.

Mapping the information flow from one brain to another during gestural communication.

Both the putative mirror neuron system (pMNS) and the ventral medial prefrontal cortex (vmPFC) are deemed important for social interaction: the pMNS because it supposedly "resonates" with the actions of others, the vmPFC because it is involved in mentalizing. Strictly speaking, the resonance property of the pMNS has never been investigated. Classical functional MRI experiments have only investigated whether pMNS regions augment their activity when an action is seen or executed. Resonance, however, entails more than only "going on and off together". Activity in the pMNS of an observer should continuously follow the more subtle changes over time in activity of the pMNS of the actor. Here we directly explore whether such resonance indeed occurs during continuous streams of actions. We let participants play the game of charades while we measured brain activity of both gesturer and guesser. We then applied a method to localize directed influences between the brains of the participants: between-brain Granger-causality mapping. Results show that a guesser's brain activity in regions involved in mentalizing and mirroring echoes the temporal structure of a gesturer's brain activity. This provides evidence for resonance theories and indicates a fine-grained temporal interplay between regions involved in motor planning and regions involved in thinking about the mental states of others. Furthermore, this method enables experiments to be more ecologically valid by providing the opportunity to leave social interaction unconstrained. This, in turn, would allow us to tap into the neural substrates of social deficits such as autism spectrum disorder.

Probabilistic tractography recovers a rostrocaudal trajectory of connectivity variability in the human insular cortex.

The insular cortex of macaques has a wide spectrum of anatomical connections whose distribution is related to its heterogeneous cytoarchitecture. Although there is evidence of a similar cytoarchitectural arrangement in humans, the anatomical connectivity of the insula in the human brain has not yet been investigated in vivo. In the present work, we used in vivo probabilistic white-matter tractography and Laplacian eigenmaps (LE) to study the variation of connectivity patterns across insular territories in humans. In each subject and hemisphere, we recovered a rostrocaudal trajectory of connectivity variation ranging from the anterior dorsal and ventral insula to the dorsal caudal part of the long insular gyri. LE suggested that regional transitions among tractography patterns in the insula occur more gradually than in other brain regions. In particular, the change in tractography patterns was more gradual in the insula than in the medial premotor region, where a sharp transition between different tractography patterns was found. The recovered trajectory of connectivity variation in the insula suggests a relation between connectivity and cytoarchitecture in humans resembling that previously found in macaques: tractography seeds from the anterior insula were mainly found in limbic and paralimbic regions and in anterior parts of the inferior frontal gyrus, while seeds from caudal insular territories mostly reached parietal and posterior temporal cortices. Regions in the putative dysgranular insula displayed more heterogeneous connectivity patterns, with regional differences related to the proximity with either putative granular or agranular regions.

Heuristics for connectivity-based brain parcellation of SMA/pre-SMA through force-directed graph layout.

We propose the use of force-directed graph layout as an explorative tool for connectivity-based brain parcellation studies. The method can be used as a heuristic to find the number of clusters intrinsically present in the data (if any) and to investigate their organisation. It provides an intuitive representation of the structure of the data and facilitates interactive exploration of properties of single seed voxels as well as relations among (groups of) voxels. We validate the method on synthetic data sets and we investigate the changes in connectivity in the supplementary motor cortex, a brain region whose parcellation has been previously investigated via connectivity studies. This region is supposed to present two easily distinguishable connectivity patterns, putatively denoted by SMA (supplementary motor area) and pre-SMA. Our method provides insights with respect to the connectivity patterns of the premotor cortex. These present a substantial variation among subjects, and their subdivision into two well-separated clusters is not always straightforward.

Group analyses of connectivity-based cortical parcellation using repeated k-means clustering.

K-means clustering has become a popular tool for connectivity-based cortical segmentation using Diffusion Weighted Imaging (DWI) data. A sometimes ignored issue is, however, that the output of the algorithm depends on the initial placement of starting points, and that different sets of starting points therefore could lead to different solutions. In this study we explore this issue. We apply k-means clustering a thousand times to the same DWI dataset collected in 10 individuals to segment two brain regions: the SMA-preSMA on the medial wall, and the insula. At the level of single subjects, we found that in both brain regions, repeatedly applying k-means indeed often leads to a variety of rather different cortical based parcellations. By assessing the similarity and frequency of these different solutions, we show that approximately 256 k-means repetitions are needed to accurately estimate the distribution of possible solutions. Using nonparametric group statistics, we then propose a method to employ the variability of clustering solutions to assess the reliability with which certain voxels can be attributed to a particular cluster. In addition, we show that the proportion of voxels that can be attributed significantly to either cluster in the SMA and preSMA is relatively higher than in the insula and discuss how this difference may relate to differences in the anatomy of these regions.

Flavor pleasantness processing in the ventral emotion network.

The ventral emotion network-encompassing the amygdala, insula, ventral striatum, and ventral regions of the prefrontal cortex-has been associated with the identification of emotional significance of perceived external stimuli and the production of affective states. Functional magnetic resonance imaging (fMRI) studies investigating chemosensory stimuli have associated parts of this network with pleasantness coding. In the current study, we independently analyzed two datasets in which we measured brain responses to flavor stimuli in young adult men. In the first dataset, participants evaluated eight regular off the shelf drinking products while participants evaluated six less familiar oral nutritional supplements (ONS) in the second dataset. Participants provided pleasantness ratings 20 seconds after tasting. Using independent component analysis (ICA) and mixed effect models, we identified one brain network in the regular products dataset that was associated with flavor pleasantness. This network was very similar to the ventral emotion network. Although we identified an identical network in the ONS dataset using ICA, we found no linear relation between activation of any network and pleasantness scores within this dataset. Our results indicate that flavor pleasantness is processed in a network encompassing amygdala, ventral prefrontal, insular, striatal and parahippocampal regions for familiar drinking products. For more unfamiliar ONS products the association is not obvious, which could be related to the unfamiliarity of these products.

Not on speaking terms: hallucinations and structural network disconnectivity in schizophrenia.

Auditory verbal hallucinations (AVH) in schizophrenia have previously been associated with functional deficiencies in language networks, specifically with functional disconnectivity in fronto-temporal connections in the left hemisphere and in interhemispheric connections between frontal regions. Here, we investigate whether AVH are accompanied by white matter abnormalities in tracts connecting the frontal, parietal and temporal lobes, also engaged during language tasks. We combined diffusion tensor imaging with tract-based spatial statistics and found white matter abnormalities in patients with schizophrenia as compared with healthy controls. The patients showed reduced fractional anisotropy bilaterally: in the anterior thalamic radiation (ATR), body of the corpus callosum (forceps minor), cingulum, temporal part of the superior longitudinal fasciculus (SLF) and a small area in the inferior fronto-occipital fasciculus (IFOF); and in the right hemisphere: in the visual cortex, forceps major, body of the corpus callosum (posterior parts) and inferior parietal cortex. Compared to patients without current hallucinations, patients with hallucinations revealed decreased fractional anisotropy in the left IFOF, uncinate fasciculus, arcuate fasciculus with SLF, corpus callosum (posterior parts-forceps major), cingulate, corticospinal tract and ATR. The severity of hallucinations correlated negatively with white matter integrity in tracts connecting the left frontal lobe with temporal regions (uncinate fasciculus, IFOF, cingulum, arcuate fasciculus anterior and long part and superior long fasciculus frontal part) and in interhemispheric connections (anterior corona radiata). These findings support the hypothesis that hallucinations in schizophrenia are accompanied by a complex pattern of white matter alterations that negatively affect the language, emotion and attention/perception networks.

Data modelling in corpus linguistics: how low may we go?

Corpus linguistics allows researchers to process millions of words. However, the more words we analyse, i.e., the more data we acquire, the more urgent the call for correct data interpretation becomes. In recent years, a number of studies saw the light attempting to profile some prolific authors' linguistic decline, linking this decline to pathological conditions such as Alzheimer's Disease (AD). However, in line with the nature of the (literary) work that was analysed, numbers alone do not suffice to 'tell the story'. The one and only objective of using statistical methods for the analysis of research data is to tell a story--what happened, when, and how. In the present study we describe a computerised but individualised approach to linguistic analysis--we propose a unifying approach, with firm grounds in Information Theory, that, independently from the specific parameter being investigated, guarantees to produce a robust model of the temporal dynamics of an author's linguistic richness over his or her lifetime. We applied this methodology to six renowned authors with an active writing life of four decades or more: Iris Murdoch, Gerard Reve, Hugo Claus, Agatha Christie, P.D. James, and Harry Mulisch. The first three were diagnosed with probable Alzheimer Disease, confirmed post-mortem for Iris Murdoch; this same condition was hypothesized for Agatha Christie. Our analysis reveals different evolutive patterns of lexical richness, in turn plausibly correlated with the authors' different conditions.

Dealing with consumer differences in liking during repeated exposure to food; typical dynamics in rating behavior.

Consumers show high interindividual variability in food liking during repeated exposure. To investigate consumer liking during repeated exposure, data is often interpreted on a product level by averaging results over all consumers. However, a single product may elicit inconsistent behaviors in consumers; averaging will mix and hide possible subgroups of consumer behaviors, leading to a misinterpretation of the results. To deal with the variability in consumer liking, we propose to use clustering on data from consumer-product combinations to investigate the nature of the behavioral differences within the complete dataset. The resulting behavioral clusters can then be used to describe product acceptance. To test this approach we used two independent data sets in which young adults were repeatedly exposed to drinks and snacks, respectively. We found that five typical consumer behaviors existed in both datasets. These behaviors differed both in the average level of liking as well as its temporal dynamics. By investigating the distribution of a single product across typical consumer behaviors, we provide more precise insight in how consumers divide in subgroups based on their product liking (i.e. product modality). This work shows that taking into account and using interindividual differences can unveil information about product acceptance that would otherwise be ignored.

Age-related increase in inferior frontal gyrus activity and social functioning in autism spectrum disorder.

BACKGROUND: Hypoactivation of the inferior frontal gyrus during the perception of facial expressions has been interpreted as evidence for a deficit of the mirror neuron system in children with autism. We examined whether this dysfunction persists in adulthood, and how brain activity in the mirror neuron system relates to social functioning outside the laboratory. METHODS: Twenty-one adult males with autism spectrum disorders and 21 typically developing subjects matched for age, sex, and IQ were scanned in three conditions: observing short movies showing facial expressions, performing a facial movement, and experiencing a disgusting taste. Symptom severity and level of social adjustment were measured with the Autism Diagnostic Observation Schedule and the Social Functioning Scale. RESULTS: Inferior frontal gyrus activity during the observation of facial expressions increased with age in subjects with autism, but not in control subjects. The age-related increase in activity was associated with changes in gaze behavior and improvements in social functioning. These age-related neurocognitive improvements were not found in a group of individuals with schizophrenia, who had comparable levels of social functioning. CONCLUSIONS: The results of this cross-sectional study suggest that mirror neuron system activity augments with age in autism and that this is accompanied by changes in gaze behavior and improved social functioning. It is the first demonstration of an age-related neurocognitive improvement in autism. Increased motor simulation may contribute to the amelioration in social functioning documented in adolescence and adulthood. This finding should encourage the development of new therapeutic interventions directed at emotion simulation.