Combined use of MRI, fMRIand cognitive data for Alzheimer's Disease: Preliminary results

MRI can favor clinical diagnosis providing morphological and functional information of several neurological disorders. This paper deals with the problem of exploiting both data, in a combined way, to develop a tool able to support clinicians in the study and diagnosis of Alzheimer's Disease (AD). In this work, 69 subjects from the ADNI open database, 33 AD patients and 36 healthy controls, were analyzed. The possible existence of a relationship between brain structure modifications and altered functions between patients and healthy controls was investigated performing a correlation analysis on brain volume, calculated from the MRI image, the clustering coefficient, derived from fRMI acquisitions, and the Mini Mental Score Examination (MMSE). A statistically-significant correlation was found only in four ROIs after Bonferroni's correction. The correlation analysis alone was still not sufficient to provide a reliable and powerful clinical tool in AD diagnosis however. Therefore, a machine learning strategy was studied by training a set of support vector machine classifiers comparing different features. The use of a unimodal approach led to unsatisfactory results, whereas the multimodal approach, i.e., the synergistic combination of MRI, fMRI, and MMSE features, resulted in an accuracy of 95.65%, a specificity of 97.22%, and a sensibility of 93.93%

La connectivité structurelle de l'insula chez l'humain

L'insula est une structure complexe impliquée dans une variété de fonctions. Les études de connectivité par traçage chez les primates non humains ont révélé une multitude de connexions corticales entre l'insula et les lobes frontal (cortex orbitofrontal, cortex préfrontal, régions cingulaires, aire motrice supplémentaire), pariétal (cortex somatosensoriel primaire et secondaire) et temporal (pôle temporal, cortex auditif, cortex prorhinal et entorhinal). Les études de tractographie chez l'humain ont révélé des connexions structurelles similaires, mais n'ont pas rapporté de connexion avec le cortex cingulaire, malgré que cette structure soit reconnue comme étant fonctionnellement connectée à l’insula. Ce projet vise à approfondir la recherche sur la connectivité structurelle entre ces deux structures ainsi que d'autres régions connues comme étant fonctionnellement connectées à l'insula, à l'aide d'un échantillon plus grand et des plus récentes méthodes en tractographie par l’imagerie à haute résolution de diffusion angulaire basée sur des a priori anatomiques. En analysant les données de 46 participants adultes en bonne santé, notre étude rapporte un large éventail de connexions entre l’insula et les lobes frontal, temporal, pariétal et occipital ainsi que les régions limbiques, suivant un patron d’organisation rostrocaudal. Notamment, nous démontrons pour la première fois une connexion structurelle claire entre l’insula et les gyri cingulaire, parahippocampique, supramarginal et angulaire ainsi que le précunéus et les régions occipitales.The insula is a complex structure involved in a wide range of functions. Tracing studies on non-human primates reveal a wide array of cortical connections in the frontal (orbitofrontal and prefrontal cortices, cingulate areas, and supplementary motor area), parietal (primary and secondary somatosensory cortices) and temporal (temporal pole, auditory, prorhinal and entorhinal cortices) lobes. However, recent human tractography studies have not observed connections between the insula and the cingulate cortices, although these structures are thought to be functionally intimately connected. In this work, we try to unravel the structural connectivity between these regions and other known functionally connected structures, benefiting from a higher number of subjects and the latest state-of-the-art high angular resolution diffusion imaging (HARDI) tractography algorithms with anatomical priors. By performing a HARDI tractography analysis on 46 young normal adults, our study reveals a wide array of connections between the insula and the frontal, temporal, parietal and occipital lobes as well as limbic regions, with a rostro-caudal organization in line with tracing studies in macaques. Notably, we reveal for the first time in humans a clear structural connectivity between the insula and the cingulate, parahippocampal, supramarginal and angular gyri as well as the precuneus and occipital regions

Brain mechanisms of audiotactile and audiomotor interactions

This thesis focuses on audiotactile integration, brain areas activated by vibrotactile stimulation, transfer of vibrotactile information to motor output, and reactivity of the human primary motor and somatosensory cortices in action observation. Human experience of the outside world results from integration of information obtained simultaneously via multiple senses. Accumulating evidence, from studies in both primates and humans, suggests that integration between different sensory modalities also occurs at early stages of cortical processing, in areas classically considered as purely unisensory. In Study I we studied integration between auditory and somatosensory systems. We showed, in a loudness-matching task, that subjects chose lower intensities for the probe than for the reference tone, when auditory and vibrotactile stimuli were presented simultaneously. In Studies II and III we explored brain areas involved in processing vibrotactile and tactile information, respectively. We showed that, besides primary and secondary somatosensory areas, auditory areas are also activated. In Study II we characterized the time course of brain activations and showed convergence of vibrotactile information to auditory areas. On the other hand, in Study III we identified, with good spatial accuracy, common neural substrates that process auditory and tactile information in auditory belt areas. In Study IV we assessed whether frequency information transfers from touch to vocal utterance in normal-hearing female adults. We demonstrated that such information transfer occurs clearly between 150–400 Hz. Based on findings in Studies II and III, we hypothesized that this transfer may involve at least primary and secondary somatosensory and auditory areas. Our social skills rely on the capability to understand others. In the human brain, the mirror-neuron system matches observation and execution of actions. This system comprises at least the inferior frontal gyrus, premotor areas, primary motor cortex, and the inferior parietal lobule. In Study V we investigated similarities in sensorimotor oscillatory activity between own, observed, and heard actions. We demonstrated that the primary motor cortex is activated before own and observed actions and stabilizes similarly. We also showed that rhythmic activity in the primary somatosensory cortex recovers later during own actions, which may be related to proprioceptive input and contribute to maintaining the sense of agency.reviewe

Magnetoenkefalografian ja toiminnallisen magneettikuvauksen vertailu ja yhdistäminen tunto- ja liikejärjestelmän tutkimuksessa

MEG directly measures the neuronal events and has greater temporal resolution than fMRI, which has limited temporal resolution mainly due to the larger timescale of the hemodynamic response. On the other hand fMRI has advantages in spatial resolution, while the localization results with MEG can be ambiguous due to the non-uniqueness of the electromagnetic inverse problem. Thus, these methods could provide complementary information and could be used to create both spatially and temporally accurate models of brain function. We investigated the degree of overlap, revealed by the two imaging methods, in areas involved in sensory or motor processing in healthy subjects and neurosurgical patients. Furthermore, we used the spatial information from fMRI to construct a spatiotemporal model of the MEG data in order to investigate the sensorimotor system and to create a spatiotemporal model of its function. We compared the localization results from the MEG and fMRI with invasive electrophysiological cortical mapping. We used a recently introduced method, contextual clustering, for hypothesis testing of fMRI data and assessed the the effect of neighbourhood information use on the reproducibility of fMRI results. Using MEG, we identified the ipsilateral primary sensorimotor cortex (SMI) as a novel source area contributing to the somatosensory evoked fields (SEF) to median nerve stimulation. Using combined MEG and fMRI measurements we found that two separate areas in the lateral fissure may be the generators for the SEF responses from the secondary somatosensory cortex region. The two imaging methods indicated activation in corresponding locations. By using complementary information from MEG and fMRI we established a spatiotemporal model of somatosensory cortical processing. This spatiotemporal model of cerebral activity was in good agreement with results from several studies using invasive electrophysiological measurements and with anatomical studies in monkey and man concerning the connections between somatosensory areas. In neurosurgical patients, the MEG dipole model turned out to be more reliable than fMRI in the identification of the central sulcus. This was due to prominent activation in non-primary areas in fMRI, which in some cases led to erroneous or ambiguous localization of the central sulcus.Magnetoenkefalografia (MEG) mittaa suoraan aivojen hermosolujen sähköistä toimintaa ja sillä on parempi ajallinen erotuskyky kuin aivojen aktivaation aiheuttamia paikallisen verenkierron muutoksia kuvaava toiminnallinen magneettikuvaus (TMK). TMK:lla on toisaalta etuja paikannuksessa MEG:hen nähden ja MEG:llä saadut paikannustulokset ovat monikäsitteisiä. Nämä menetelmät voivat täydentää toisiaan ja yhdessä niillä voidaan saada tarkempi ajallinen ja paikallinen kuva aivojen toiminnasta. Käytimme näitä kahta menetelmää aivojen tunto- ja liikejärjestelmän toiminnan kuvantamisessa terveillä koehenkilöillä ja neurokirurgisilla potilailla. Tutkimme menetelmillä saatavan paikannustuloksen yhteneväisyyttä ja käytimme TMK:sta saatavaa paikannustietoa MEG:llä mitattujen aivojen magneetisten vasteiden mallinuksessa luoden mallin aivojen tuntojärjestelmän toiminnasta. Neurokirurgisilla potilailla vertasimme kuvantamismenetelmien tuloksia leikkauksenaikaiseen sähköiseen liikeaivokuoren paikannukseen. Tutkimuksessa testattiin ja sovellettin kehittämiämme uusia kuva-analyysimenetelmiä. MEG:llä ja TMK:lla havaitsimme viitteitä aktivaatiosta tuntoärsykkeen kanssa samanpuoleisella primäärillä tuntoaivokuorella. Tuloksemme viittaavat lisäksi siihen että aivojen lateraalisessa fissuurassa on ainakin kaksi erillistä lähdealuetta jotka tuottavat magneettisia tuntoherätevasteita. Mallimme aivojen toiminnasta tuntoarsykkeen käsittelyn aikana vastasi hyvin kirjallisuudessa raportoituja suoraan aivoista mitattuja eri alueiden aktivaatioaikoja. TMK-analyysimenetelmiä vertailtaessa todettiin kuva-alkion naapurustoinformaatiota käyttävien menetelmien tuottavan paremmin toistettavia tuloksia. Kehittämämme menetelmä rajasi tarkemmin aivojen aktivaatioalueen ja oli muita menetelmiä herkempi havaitsemaan heikkoja aktivaatioita. Paikannettaessa aivojen keskusuurretta leikkauksen suunnittelua ja riskien arviointia varten MEG tuotti luotettavamman tuloksen kuin TMK jossa osalla potilaista aktivaatiot muilla kuin primäärillä liikeaivokuorella olivat voimakkaimpia vaikeuttaen tulosten tulkintaa

The neural correlates of reading impairment in adults with developmental dyslexia:evidence from fMRI between group analyses and an fMRI multiple-case study

The goal of this project was to investigate the neural correlates of reading impairment in dyslexia as hypothesised by the main theories – the phonological deficit, visual magnocellular deficit and cerebellar deficit theories, with emphasis on individual differences. This research took a novel approach by: 1) contrasting the predictions in one sample of participants with dyslexia (DPs); 2) using a multiple-case study (and between-group comparisons) to investigate differences in BOLD between each DP and the controls (CPs); 3) demonstrating a possible relationship between reading impairment and its hypothesised neural correlates by using fMRI and a reading task. The multiple-case study revealed that the neural correlates of reading in dyslexia in all cases are not in agreement with the predictions of a single theory. The results show striking individual differences - even, where the neural correlates of reading in two DPs are consistent with the same theory, the areas can differ. A DP can exhibit under-engagement in an area in word, but not in pseudoword reading and vice versa, demonstrating that underactivation in that area cannot be interpreted as a ‘developmental lesion’. Additional analyses revealed complex results. Within-group analyses between behavioural measures and BOLD showed correlations in the predicted regions, areas outside ROI, and lack of correlations in some predicted areas. Comparisons of subgroups which differed on Orthography Composite supported the MDT, but only for Words. The results suggest that phonological scores are not a sufficient predictor of the under-engagement of phonological areas during reading. DPs and CPs exhibited correlations between Purdue Pegboard Composite and BOLD in cerebellar areas only for Pseudowords. Future research into reading in dyslexia should use a more holistic approach, involving genetic and environmental factors, gene by environment interaction, and comorbidity with other disorders. It is argued that multidisciplinary research, within the multiple-deficit model holds significant promise here