HUMAN BRAIN WHITE MATTER ANALYSIS USING TRACTOGRAPHY —AN ATLAS-BASED APPROACH

The human brain is connected via a vastly complex network of white matter fiber pathways. However, this structural connectivity information cannot be obtained from conventional MRI, in which much of white matter appears homogeneous. Diffusion tensor imaging can estimate fiber orientation by measuring the anisotropy of water diffusion. Using tractography, the brain connectivity can be studied non-invasively. Past tractography studies have shown that the cores of prominent white matter tracts can be faithfully reconstructed. Superimposing the tract coordinates on various MR images, MR metrics can be quantified in a tract-specific manner. However, tractography results are often contaminated by partial volume effect and imaging noise. Particularly, tractography often fails under white matter pathological conditions, which render tract-specific analysis impractical. In order to address these issues, we introduced an atlas-based approach. Four novel atlas-based approaches were included in this data analysis framework. First, statistical templates of major white matter tracts were created using a DTI database of normal subjects. The statistical white matter tract templates can serve two purposes. First, the statistical template can be used as a reference to detect abnormal white matter anatomy in neurodegenerative diseases. Second, the statistical template can be applied to individual patient data for automated white matter parcellation and tract-specific quantification. In the second approach, the trajectory of white matter fiber bundles was used to estimate the cortical regions associated with specific tracts of interest. Using this approach, cortical regions were reproducibly identified on the population-averaged cortical maps of brain connectivity. Third, we improved the accuracy of the population-based tract analysis by incorporating a highly elastic image transformation technique, called Large Deformation Diffeomorphic Metric Mapping (LDDMM). As a testament to the power of this algorithm, we successfully applied tract-specific analysis on Alzheimer’s patients. The last approach was to analyze the brain cortical connection networks using automatic fiber tracking. A tracking pipeline was built by combining White Matter Parcellation Map (WMPM), brute-force tractography and topology-preserving image transformation LDDMM. This novel tracking pipeline was applied on patient group with Alzheimer’s disease. The connectivity networks of Alzheimer’s patients were compared with age-matched controls using multivariate pattern classification

Methods for improved mapping of brain lesion connectivity

Recent advances over the past two decades in neuroimaging methods have enabled us to map the connectivity of the brain. In parallel, pathophysiological models of brain disease have shifted from an emphasis on understanding pathology in specific brain regions to characterizing disruptions to interconnected neural networks. Nevertheless, these recent methods for mapping brain connectivity are still under development. Every step of the mapping process becomes a potential source for additional error due to noise or artifacts that could impact final analyses. Segmentation, parcellation, registration, and tractography are some of the steps where this occurs. Moreover, mapping the connectivity in a brain lesion is even more susceptible to errors in these steps. In this body of work, I describe multiple new methods for improving the accuracy of mapping lesion connectivity by reducing errors at the tractography stage which is the most error prone stage. First, we develop an approach for directly normalizing streamlines into a template space that avoids performing tractography in the normalized template space, reducing the error of connectomes constructed in the template space with respect to the ground truth native space connectome. Second, we develop a rapid approach for performing shortest path tractography and constructing shortest path probability weighted connectomes which increases the connection specificity relative to local streamline tracking approaches. We then demonstrate how our shortest path tractography approach can be used construct a disconnectome, a connectivity map of the proportion of connections lost due to intersecting a lesion. We then develop a fast, greedy graph-theoretic algorithm that extracts the maximally disconnected subgraph containing brain regions with the greatest shared loss of connectivity. Finally, we demonstrate how combining methods from diffusion based image inpainting and optimal estimation can be used to restore or inpaint corrupted fiber diffusion models in lesioned white matter tissue, enabling tractography and the study of lesion connectivity and modeling of microstructural measures in the patient’s native space

Development and application of a human cortical brain atlas on MRI considering phylogeny = Développement et emploi d'un atlas du cortex cérébral humain réalisé sur IRM et tenant compte de la phylogénie

Le cortex cérébral est une structure en couches complexe qui remplit différents types de fonctions. Au cours de l’histoire des neurosciences, plusieurs atlas corticaux ont été développés pour classifier différentes régions du cortex en tant que zones aux caractéristiques structurelles ou fonctionnelles communes, afin d'étudier et de quantifier les changements aux états sain et pathologique. Cependant, il n'existe pas d'atlas suivant une approche phylogénétique, c'est-à-dire, basée sur les critères d'évolution communs. Ce mémoire présente les étapes de création d'un nouvel atlas dans un modèle d’imagerie par résonance magnétique (IRM) en espace standard (pseudo-Talairach) : le PAN-Atlas, basé sur l'origine phylogénétique commune de chaque zone corticale, et son application sur des scans d’IRM de dix individus pour évaluer sa performance. D’abord, nous avons regroupé les différentes régions corticales en cinq régions d'intérêt (RdI) d'origine phylogénétique connue (archicortex, paléocortex, périarchicortex, proïsocortex, isocortex ou néocortex) sur la base de protocoles de segmentation validés histologiquement par d'autres groupes de chercheurs. Puis, nous avons segmenté ces régions manuellement sur le modèle d’IRM cérébrale moyen MNI-ICBM 2009c, en formant des masques. Par la suite, on a utilisé un pipeline multi-étapes de traitement des images pour réaliser le recalage des masques de notre atlas aux scans pondérés T1 de dix participants sains, en obtenant ainsi des masques automatiques pour chaque RdI. Les masques automatiques ont été évalués après une correction manuelle par le biais de l’indice Dice-kappa, qui quantifie la colocalisation des voxels de chaque masque automatique vs. le masque corrigé manuellement. L’indice a montré une très bonne à excellente performance de notre atlas. Cela a permis l’évaluation et comparaison des volumes corticales de chaque région et la quantification des valeurs de transfert de magnétisation (ITM), qui sont sensibles à la quantité de myéline présente dans le tissu. Ce travail montre que la division régionale du cortex en IRM avec une approche phylogénétique est réalisable à l'aide de notre PAN-Atlas en espace standard et que les masques peuvent être utilisés pour différents types de quantifications, comme les volumes corticaux, ou l’estimation des valeurs de ITM. Notre atlas pourrait éventuellement servir à évaluer les différences entre personnes saines et celles atteintes par des maladies neurodégénératives ou d’autres maladies neurologiques.The cerebral cortex is a complex layered structure that performs different types of functions. Throughout the history of neuroscience, several cortical atlases have been developed to classify/divide different regions of the cortex into areas with common structural or functional characteristics, to then study and quantify changes in healthy and pathological states. However, to date, there is no atlas following a phylogenetic approach, i.e. based on the common evolution criteria. This thesis presents the steps of creation of a new atlas corresponding to a standard MRI template: the PAN-Atlas, based on the common phylogenetic origin of each cortical zone, and its application on MRI scans of ten healthy participants to assess its performance. First, we grouped the different cortical regions into five regions of interest (ROI) of known phylogenetic origin (archicortex, paleocortex, periarchicortex, proisocortex, isocortex or neocortex) based on MRI protocols previously validated through histology by other groups of researchers. Then, we manually segmented these ROIs on the MNI-ICBM 2009c average brain MRI template, creating corresponding masks. We then used a multi-step image processing pipeline to register the atlas’ masks to T1 weighted images of ten healthy participants, generating automatic masks for each scan. The accuracy of these automatic atlas’ masks was assessed after manual correction using Dice-kappa similarity index, to quantify the colocalization of the automatic vs. the manually corrected masks. The Dice-kappa values showed a very good to excellent performance of the automatic atlas’ masks. This allowed the evaluation and comparison of cortical volumes of each ROI, as well as the quantification of magnetization transfer ratio (MTR) values, which are sensitive to myelin content. This work shows that the division of the cortex on MRI following a phylogenetic approach is feasible using our PAN Atlas, and that the masks of the atlas can be used to perform different types of quantifications, such as the ones presented here (cortical volume and MTR per ROI). Our atlas could similarly be used to assess differences between the cortex of healthy individuals and people affected by neurodegenerative diseases and other neurological disorders

Functional and anatomical brain networks : Brain networks during naturalistic auditory stimuli, tactile stimuli and rest : Functional network plasticity in early-blind subjects.

Hearing is a versatile sense allowing us, among other things, to avoid danger and engage in pleasurable discussions. The ease with which we follow a conversation in a noisy environment is astonishing. Study I in this thesis used functional magnetic resonance imaging to explore the large-scale organization of speech and non-speech sound processing during a naturalistic stimulus comprised of an audio drama. Two large-scale functional networks processed the audio drama; one processed only speech, the other processed both speech and non-speech sounds. Hearing is essential for blind subjects. Anatomical and functional changes in the brains of blind people allow them to experience a detailed auditory world, compensating for the lack of vision. Therefore, comparing early-blind subjects brains to those of sighted people during naturalistic stimuli reveals fundamental differences in brain organization. In Study II, naturalistic stimuli were employed to explore whether one of the most distinguishing traits of the auditory system the left-lateralized responses to speech changes following blindness. As expected, in sighted subjects, speech processing was left-hemisphere dominant. Curiously, the left-hemisphere dominance for speech was absent or even reversed in blind subjects. In early-blind people, the senses beyond vision are strained as they try to compensate for the loss of sight; on the other hand, the occipital cortices are devoid of normal visual information flow. Interestingly, in blind people, senses other than vision recruit the occipital cortex. Additional to changes in the occipital cortex, the sensory cortices devoted to touch and hearing change. Data presented here suggested more inter-subject variability in auditory and parietal areas in blind subjects compared with sighted subjects. The study suggested that the greater the inter-subject variability of the network, the greater the experience-dependent plasticity of that network. As the prefrontal areas display large inter-subject spatial variability, the activation of the prefrontal cortex varies greatly. The variable activation might partly explain why the top-down influences of the prefrontal cortex on tactile discrimination are not well understood. In the fourth study, anatomical variability was assessed on an individual level, and transcranial magnetic stimulation was targeted at individually-chosen prefrontal locations indicated in tactile processing. Stimulation of one out of two prefrontal cortex locations impaired the subjects ability to distinguish a single tactile pulse from paired pulses. Thus, the study suggested that tactile information is regulated by functionally specialized prefrontal subareas.Anatomiska och funktionella hjärnnätverk hos seende och synskadade Hörseln är möjligen vårt viktigaste sinne. Med hjälp av hörseln kan vi bl.a. undvika faror och enkelt skilja mellan tal och oljud. I den första delen av avhandlingen fick försökspersonerna lyssna till en radiopjäs medan de undergick funktionell magnetresonanstomografi. Vi fann två olika hjärnnätverk som behandlade pjäsen. Det ena reagerade på både tal och andra ljud, medan det andra registrerade enbart tal. Synskadade klarar sig väl i vardagslivet, detta anses påvisa hjärnans förmåga att anpassa sig till begränsningar i dess normala funktion. I andra delen av avhandlingen jämfördes sedan ungdomen synskadade med seende. Det framgick att seende reagerade starkare på tal med den vänstra hjärnhalvan. Tidigt synskadade visade inga skillnader mellan hjärnhalvorna i reaktivitet till tal. Hos blinda rör det sig naturligtvis inte synintryck i syncortex. Detta medför att tidigt i livet synskadade brukar syncortex för att bearbeta hörsel- och känselintryck. Funktionell magnetresonanstomografi har möjliggjort att undersöka hur synskadade personers hjärnor förändrat sig. I tredje delen av avhandlingen påvisades att synskadade hade en större individuella skillnader i tal- och hörselcortex. Syncortex däremot hade större individuella skillnader hos seende. Det kan tyda på att ökningen av de individuella skillnaderna speglar hjärnans adaptionsmekanismer. En orsak till vår bristfälliga kunskap on frontallobens sammansättning kan ligga i de stora individuella variationerna. Vätskediffusions-MR kan påvisa anatomiska nervbanor på en individuell nivå. I avhandlingens fjärde del utvärderades anatomiska kontakter på individnivå. Sedan användes transkraniell magnetstimulering för att aktivera utvalda nervbanor mellan frontalloben och känslocortex medan vi observerade försökspersonernas förmåga att särskilja antalet känslostötar. Försökspersoner kunde inte urskilja mängden känslostötar ifall ett visst område av frontalloben stimulerades.Sokeiden ja näkevien aivoverkot Tämän väitöskirjatyön tavoitteena oli selvittää aivoverkkojen ominaisuuksia levossa, sekä tunto- ja ääniärsykkeiden aikana. Tarkemmat tavoitteet olivat seuraavat: 1) Tutkia, miten luonnonmukainen ääniärsyke käsitellään näkevien ja sokeiden koehenkilöiden aivoverkoissa. 2) Tutkia toiminnallisten aivoverkkojen yksilöllisiä eroja sokeilla ja näkevillä. 3) Selvittää miten etuaivolohkon ja tuntoaivokuoren välisen hermorata-yhteyden ärsyttäminen vaikuttaa tuntoärsykkeen käsittelyyn. Kuulo on mahdollisesti tärkein aistimme. Kuuloaistin avulla mm. vältämme vaaroja ja erotamme vaivattomasti puheen ympäröivästä melusta. Tämän väitöksen ensimmäisessä osatyössä tutkittavat kuuntelivat ääninäytelmää aivojen toiminnallisen magneettikuvauksen aikana. Tutkimuksessa havaittiin kaksi erillistä ääninäytelmää käsittelevää toiminnallista aivoverkkoa. Toinen käsitteli puheääniä ja ympäristöääniä, toinen pelkästään puheääniä. Sokeat pärjäävät hyvin arkielämässä. Tätä pidetään osoituksena aivojen kyvystä paikata puuttuvaa näköaistia muovautumalla. Toisessa osatyössä tutkittiin, miten varhain sokeutuneiden aivot käsittelevät ääninäytelmää. Kun varhain sokeutuneiden koehenkilöiden aivojen toimintaa verrattiin näkevien aivojen toimintaan, paljastui, että näkevillä vasen aivopuolisko reagoi puheeseen oikeata aivopuoliskoa vahvemmin, kun taas sokeilla tämä aivopuoliskojen välinen ero ei tullut esille. Sokeilla kuuloaivokuori korvaa näköaistin puutetta, toisaalta näköaivokuorelle ei tule näköaistin tuottamia viestejä. Tästä seuraa, että varhain sokeutuneilla muut aistit valtaavat näköaivokuoren. Aivojen toiminnallinen magneettikuvaus sekä uudet analyysimenetelmät ovat mahdollistaneet sokeiden aivojen muovautumisen tutkimisen. Tässä väitöskirjatyössä käytettiin uusia analyysimenetelmiä sokeiden ja näkevien aivokuoren toiminnan muovautumisen tutkimiseen. Osoitimme, että sokeilla oli näkeviä enemmän yksilöllistä vaihtelua puhe- ja kuuloaivokuoren toiminnassa. Näköaivokuoren toiminnassa sokeilla oli vähemmän yksilöllistä vaihtelua kuin näkevillä. Päättelimme, että yksilöllisen vaihtelevuuden lisääntyminen oli osoitus sokeuden seurauksena tapahtuneesta aivojen muovautumisesta. Yhtenä syynä etuaivolohkon järjestäytymisen puutteelliseen tuntemiseen voi olla etuaivolohkon toiminnan suuri yksilöllinen vaihtelevuus. Diffuusiopainotteinen aivokuvantaminen yhdistettynä traktografiaan paljastaa anatomisia hermoratayhteyksiä yksilötasolla. Neljännessä osatyössä arvioimme näitä menetelmiä käyttäen tuntoaivokuoren ja etuaivolohkon anatomisia yhteyksiä yksilötasolla, ja ärsytimme näitä kohteita käyttäen nk. transkraniaalista magneettistimulaatiota (TMS). Kun otsalohkon toimintaa näin häirittiin yksilöllisesti tarkasti suunnatulla TMS pulssilla, tutkittavien kyky eritellä tuntopulssien määrää häiriintyi. Työ osoitti, että otsalohkon etuosa säätelee tuntoaivokuoren toimintaa

Brain structural predispositions for music and language processing

[eng] It has been shown that music and language training can elicit plastic changes on brain structure and function bringing along behavioural benefits. For instance, musicians have been reported to have better auditory discrimination including pitch and speech-in-noise perception, motor-synchronization, verbal memory and general IQ than individuals without formal musical background. Also, bilinguals have shown higher executive function and attention-related abilities than monolinguals. Furthermore, altered functional and structural connectivity can be tracked to brain areas related to the activities most frequently performed by both musicians (instrumentalists and singers) and linguistic experts (such as bilinguals or professional phoneticians). While research in the last decade has devoted important effort to the study of brain plasticity, only a few investigations have addressed the connection between the initial functional or structural properties of brain networks related to auditory-motor function and subsequent language or musical training. Indeed, brain structural markers such as grey matter volume/density or white-matter diffusivity measurements from diffusion tensor imaging (DTI) data, as well as functional measurements from task- related activity or resting-state data from magnetic resonance imaging (MRI) or electroenceplhalography (EEG) have been demonstrated to correlate with consecutive performance and learning in the auditory-motor domain. The main goal of the present dissertation was twofold: we aimed to further the existing knowledge regarding brain plasticity elicited during putative sensitive periods and after long-term music practice, and to explore the white-matter pathways that predict linguistic or musical skills at baseline . Our secondary goals were to confirm previous findings regarding the brain structures involved in music and language processing, as well as to provide evidence of the benefits of usingstructural measurements and correlational analyses between imaging and behavioural data to study inter-individual differences. Study I focused on the comparison between professional pianists and non- musicians observing a complex pattern of increases and decreases in grey matter volume. In comparison to non-musician individuals, pianists showed greater grey matter volume in areas related to motor skill and the automatization of learned movements, as well as reinforcement learning and emotional processing. On the other hand, regions associated to sensorimotor control, score reading and auditory and musical perception presented a reduction in grey matter volume. Study II explored the relationship between white-matter structural properties of the arcuate fasciculus (AF) and the performance of native German speakers in a foreign- language (Hindi) sentence and word imitation task. We found that a greater left lateralization of the AF volume predicted performance on the imitation task. This result was confirmed by using not only a manual deterministic approach but also an automatic atlas-based fibre-reconstruction method, which in addition pointed out to a specific region in the anterior half of the left AF as the most related to imitation ability. Study III aimed to investigate whether the white-matter structural connectivity of the pathways previously described as targets for plasticity mechanisms in professional musicians predicted musical abilities in non-musicians. We observed that the white- matter microstructural organization of the right hemisphere pathways involved in motor-control (corticospinal tract) and auditory-motor transformations (AF) correlated with the performance of non-musician individuals during the initial stages of rhythmic and melodic learning. The present work confirmed the involvement of several brain structures previously described to display plastic effects associated to music and language training in the first stages of audio-motor learning. Furthermore, they challenge previous views regarding music-induced plasticity by showing that expertise is not always or uniquely correlated with increases in brain tissue. This raises the question of the role of efficiency mechanisms derived from professional-like practice. Most importantly, the results from these three studies converge in showing that a prediction-feedback-feedforward loop for auditory-motor processing may be crucially involved in both musical and language learning and skills. We thus suggest that brain auditory-motor systems previously described as participating in native language processing (cortical areas of the dorsal route for language processing and the AF that connects them) may also be recruited during exposure to new linguistic or musical material, being refined after sustained music practice.[spa] Estudios previos muestran que la formación musical y lingüística provoca cambios plásticos en las estructuras y funciones cerebrales, acompañándose también de beneficios conductuales. Por ejemplo, se ha descrito que los músicos poseen mejores habilidades de discriminación auditiva (incluyendo la percepción tonal y la discriminación del habla en un ambiente ruidoso), una mayor capacidad de sincronización motora, así como mejor memoria verbal y coeficiente intelectual general en comparación con personas sin formación musical. Paralelamente, los bilingües muestran mejores funciones ejecutivas y habilidades relacionadas con la atención en comparación con individuos monolingües. Además, las alteraciones en la conectividad cerebral funcional y estructural pueden ser rastreadas estudiando las áreas cerebrales relacionadas con las actividades más utilizadas por músicos (instrumentistas y cantantes) y expertos lingüísticos (como bilingües o fonetistas profesionales). Pese a que en la última década se han dedicado esfuerzos importantes en el campo de la investigación sobre la plasticidad cerebral, sólo unos pocos estudios han tratado de investigar la conexión entre las propiedades iniciales del cerebro, en cuanto a las funciones y estructuras que se relacionan con las funciones auditivo-motoras, y el posterior aprendizaje musical o del lenguaje. Sin embargo, los marcadores estructurales cerebrales, tales como volumen/densidad de materia gris o medidas de difusividad en la sustancia blanca a partir de datos de imagen del tensor de difusión, así como medidas funcionales de la actividad relacionada con una tarea o datos de resting-state (estado de reposo) obtenidos por resonancia magnética o electroencefalografía, han demostrado que pueden correlacionar con el rendimiento y el aprendizaje en el dominio auditivo- motor. En la presente tesis pretendíamos ampliar nuestro conocimiento en cuanto a la plasticidad cerebral obtenida durante los supuestos “períodos sensibles” y después de la práctica musical mantenida en el tiempo, por un lado, y explorar las vías de sustancia blanca que pueden predecir habilidades lingüísticas o musicales al inicio del aprendizaje, por otro lado. Como objetivos secundarios, queríamos confirmar resultados previos con respecto a las estructuras cerebrales involucradas en el procesamiento de la música y el lenguaje, así como apoyar el uso de mediciones estructurales y enfoques correlacionales (entre datos de neuroimagen y conductuales) para estudiar las diferencias inter- individuales. El Estudio I se centró en la comparación entre pianistas profesionales y no músicos, observando un complejo patrón de aumentos y disminuciones en el volumen de materia gris. En comparación con los individuos no músicos, los pianistas mostraron mayor volumen de sustancia gris en áreas relacionadas con la habilidad motora y la automatización de movimientos aprendidos, así como el aprendizaje a través del refuerzo y el procesamiento emocional, mientras que las regiones asociadas al control sensoriomotor, lectura de partituras y percepción auditiva y musical presentaron una reducción del volumen de materia gris. El Estudio II exploró la relación entre las propiedades estructurales de la materia blanca del fascículo arqueado (AF por sus siglas en inglés) y el rendimiento de hablantes nativos de alemán en una tarea de imitación de frases y palabras en una lengua extranjera (hindi). Encontramos que una mayor lateralización del volumen de AF hacia la izquierda predecía el desempeño en la tarea de imitación. Este resultado se confirmó utilizando no sólo un enfoque determinístico-manual sino también una reconstrucción automática (basada en atlas anatómicos) de las fibras de sustancia blanca que, además, señalaba una región específica en la mitad anterior del AF izquierdo como la más relacionada con las capacidades de imitación. El Estudio III tenía como objetivo investigar si la conectividad estructural de vías de sustancia blanca anteriormente descritas como dianas para los mecanismos de plasticidad en músicos profesionales, podría predecir las habilidades musicales en los no músicos. Se observó que la organización micro-estructural de la materia blanca en el hemisferio derecho en vías involucradas en el control motor (tracto corticoespinal) y en transformaciones auditivo-motoras (AF) correlacionaba con el desempeño de individuos no músicos en las etapas iniciales del aprendizaje rítmico y melódico. El presente trabajo ha confirmado la implicación en las primeras etapas del aprendizaje audio-motor de varias estructuras cerebrales que previamente habían mostrado efectos plásticos asociados al aprendizaje musical y del lenguaje. Además, estos resultados desafían las opiniones anteriores sobre la plasticidad inducida por la experiencia musical al demostrar que la experiencia no se correlaciona siempre ni únicamente con un aumento del tejido cerebral, y planteando así preguntas sobre los mecanismos de eficiencia derivados de la práctica musical a nivel profesional. Más importante aún es que los resultados de estos tres estudios convergen mostrando que un bucle de predicción–retroalimentación (feedback)–alimentación directa (feedforward) para el procesamiento auditivo-motor puede estar implicado de manera crucial tanto en el aprendizaje musical como en el aprendizaje de idiomas. Por tanto, sugerimos que los sistemas auditivo-motrices del cerebro, que previamente se habían descrito como participantes en el procesamiento del lenguaje nativo (áreas corticales involucradas en la vía dorsal para el procesamiento del lenguaje, y el AF, que las conecta) también pueden ser reclutados durante la exposición a material lingüístico o musical nuevo, siendo refinado tras años de práctica musical activ

Parcellation of the human sensorimotor cortex: a resting-state fMRI study

The sensorimotor cortex is a brain region comprising the primary motor cortex (MI) and the primary somatosensory (SI) cortex. In humans, investigation into these regions suggests that MI and SI are involved in the modulation and control of motor and somatosensory processing, and are somatotopically organized according to a body plan (Penfield & Boldrey, 1937). Additional investigations into somatotopic mapping in relation to the limbs in the peripheral nervous system and SI in central nervous system have further born out the importance of this body-based organization (Wall & Dubner, 1972). Understanding the nature of the sensorimotor cortex‟s structure and function has broad implications not only for human development, but also motor learning (Taubert et al., 2011) and clinical applications in structural plasticity in Parkinson‟s disease (Sehm et al., 2014), among others. The aim of the present thesis is to identify functionally meaningful subregions within the sensorimotor cortex via parcellation analysis. Previously, cerebral subregions were identified in postmortem brains by invasive procedures based on histological features (Brodmann, 1909; Vogt. & Vogt., 1919; Economo, 1926; Sanides, 1970). One widely used atlas is based on Brodmann areas (BA). Brodmann divided human brains into several areas based on the visually inspected cytoarchitecture of the cortex as seen under a microscope (Brodmann, 1909). In this atlas, BA 4, BA 3, BA 1 and BA 2 together constitute the sensorimotor cortex (Vogt. & Vogt., 1919; Geyer et al., 1999; Geyer et al., 2000). However, BAs are incapable of delineating the somatotopic detail reflected in other research (Blankenburg et al., 2003). And, although invasive approaches have proven reliable in the discovery of functional parcellation in the past, such approaches are marked by their irreversibility which, according to ethical standards, makes them unsuitable for scientific inquiry. Therefore, it is necessary to develop non-invasive approaches to parcellate functional brain regions. In the present study, a non-invasive and task-free approach to parcellate the sensorimotor cortex with resting-state fMRI was developed. This approach used functional connectivity patterns of brain areas in order to delineate functional subregions as connectivity-based parcellations (Wig et al., 2014). We selected two adjacent BAs (BA 3 and BA 4) from a standard template to cover the area along the central sulcus (Eickhoff et al., 2005). Then subregions within this area were generated using resting-state fMRI data. These subregions were organized somatotopically from medial-dorsal to ventral-lateral (corresponding roughly to the face, hand and foot regions, respectively) by comparing them with the activity maps obtained by using independent motor tasks. Interestingly, resting-state parcellation map demonstrated higher correspondence to the task-based divisions after individuals had performed motor tasks. We also observed higher functional correlations between the hand area and the foot and tongue area, respectively, than between the foot and tongue regions. The functional relevance of those subregions indicates the feasibility of a wide range of potential applications to brain mapping (Nebel et al., 2014). In sum, the present thesis provides an investigation of functional network, functional structure, and properties of the sensorimotor cortex by state-of-art neuroimaging technology. The methodology and the results of the thesis hope to carry on the future research of the sensorimotor system