891 research outputs found
Bayesian Estimation of Probabilistic Atlas for Anatomically-Informed Functional MRI Group Analyses
International audienceTraditional analyses of Functional Magnetic Resonance Imaging (fMRI) use little anatomical information. The registration of the images to a template is based on the individual anatomy and ignores functional information; subsequently detected activations are not confined to gray matter (GM). In this paper, we propose a statistical model to estimate a probabilistic atlas from functional and T1 MRIs that summarizes both anatomical and functional information and the geometric variability of the population. Registration and Segmentation are performed jointly along the atlas estimation and the functional activity is constrained to the GM, increasing the accuracy of the atlas
Tracking dynamic interactions between structural and functional connectivity : a TMS/EEG-dMRI study
Transcranial magnetic stimulation (TMS) in combination with neuroimaging techniques allows to measure the effects of a direct perturbation of the brain. When coupled with high-density electroencephalography (TMS/hd-EEG), TMS pulses revealed electrophysiological signatures of different cortical modules in health and disease. However, the neural underpinnings of these signatures remain unclear. Here, by applying multimodal analyses of cortical response to TMS recordings and diffusion magnetic resonance imaging (dMRI) tractography, we investigated the relationship between functional and structural features of different cortical modules in a cohort of awake healthy volunteers. For each subject, we computed directed functional connectivity interactions between cortical areas from the source-reconstructed TMS/hd-EEG recordings and correlated them with the correspondent structural connectivity matrix extracted from dMRI tractography, in three different frequency bands (alpha, beta, gamma) and two sites of stimulation (left precuneus and left premotor). Each stimulated area appeared to mainly respond to TMS by being functionally elicited in specific frequency bands, that is, beta for precuneus and gamma for premotor. We also observed a temporary decrease in the whole-brain correlation between directed functional connectivity and structural connectivity after TMS in all frequency bands. Notably, when focusing on the stimulated areas only, we found that the structure-function correlation significantly increases over time in the premotor area controlateral to TMS. Our study points out the importance of taking into account the major role played by different cortical oscillations when investigating the mechanisms for integration and segregation of information in the human brain
Whole-brain estimates of directed connectivity for human connectomics
Connectomics is essential for understanding large-scale brain networks but requires that individual connection estimates are neurobiologically interpretable. In particular, a principle of brain organization is that reciprocal connections between cortical areas are functionally asymmetric. This is a challenge for fMRI-based connectomics in humans where only undirected functional connectivity estimates are routinely available. By contrast, whole-brain estimates of effective (directed) connectivity are computationally challenging, and emerging methods require empirical validation.
Here, using a motor task at 7T, we demonstrate that a novel generative model can infer known connectivity features in a whole-brain network (>200 regions, >40,000 connections) highly efficiently. Furthermore, graph-theoretical analyses of directed connectivity estimates identify functional roles of motor areas more accurately than undirected functional connectivity estimates. These results, which can be achieved in an entirely unsupervised manner, demonstrate the feasibility of inferring directed connections in whole-brain networks and open new avenues for human connectomics
Adaptive microstructure-informed tractography for accurate brain connectivity analyses
Human brain has been subject of deep interest for centuries, given it's central role in controlling and directing the actions and functions of the body as response to external stimuli. The neural tissue is primarily constituted of neurons and, together with dendrites and the nerve synapses, constitute the gray matter (GM) which plays a major role in cognitive functions. The information processed in the GM travel from one region to the other of the brain along nerve cell projections, called axons. All together they constitute the white matter (WM) whose wiring organization still remains challenging to uncover. The relationship between structure organization of the brain and function has been deeply investigated on humans and animals based on the assumption that the anatomic architecture determine the network dynamics. In response to that, many different imaging techniques raised, among which diffusion-weighted magnetic resonance imaging (DW-MRI) has triggered tremendous hopes and expectations. Diffusion-weighted imaging measures both restricted and unrestricted diffusion, i.e. the degree of movement freedom of the water molecules, allowing to map the tissue fiber architecture in vivo and non-invasively. Based on DW-MRI data, tractography is able to exploit information of the local fiber orientation to recover global fiber pathways, called streamlines, that represent groups of axons. This, in turn, allows to infer the WM structural connectivity, becoming widely used in many different clinical applications as for diagnoses, virtual dissections and surgical planning. However, despite this unique and compelling ability, data acquisition still suffers from technical limitations and recent studies have highlighted the poor anatomical accuracy of the reconstructions obtained with this technique and challenged its effectiveness for studying brain connectivity. The focus of this Ph.D. project is to specifically address these limitations and to improve the anatomical accuracy of the structural connectivity estimates. To this aim, we developed a global optimization algorithm that exploits micro and macro-structure information, introducing an iterative procedure that uses the underlying tissue properties to drive the reconstruction using a semi-global approach. Then, we investigated the possibility to dynamically adapt the position of a set of candidate streamlines while embedding the anatomical prior of trajectories smoothness and adapting the configuration based on the observed data. Finally, we introduced the concept of bundle-o-graphy by implementing a method to model groups of streamlines based on the concept that axons are organized into fascicles, adapting their shape and extent based on the underlying microstructure
Human cerebellum and corticocerebellar connections involved in emotional memory enhancement
Emotional information is better remembered than neutral information. Extensive evidence indicates that the amygdala and its interactions with other cerebral regions play an important role in the memory-enhancing effect of emotional arousal. While the cerebellum has been found to be involved in fear conditioning, its role in emotional enhancement of episodic memory is less clear. To address this issue, we used a whole-brain functional MRI approach in 1,418 healthy participants. First, we identified clusters significantly activated during enhanced memory encoding of negative and positive emotional pictures. In addition to the well-known emotional memory-related cerebral regions, we identified a cluster in the cerebellum. We then used dynamic causal modeling and identified several cerebellar connections with increased connection strength corresponding to enhanced emotional memory, including one to a cluster covering the amygdala and hippocampus, and bidirectional connections with a cluster covering the anterior cingulate cortex. The present findings indicate that the cerebellum is an integral part of a network involved in emotional enhancement of episodic memory
Relationship between large-scale structural and functional brain connectivity in the human lifespan
The relationship between the anatomical structure of the brain and its functional organization
is not straightforward and has not been elucidated yet, despite the growing interest this topic
has received in the last decade. In particular, a new area of research has been defined in these
years, called \u2019connectomics\u2019: this is the study of the different kinds of \u2019connections\u2019 existing
among micro- and macro-areas of the brain, from structural connectivity \u2014 described by
white matter fibre tracts physically linking cortical areas \u2014 to functional connectivity \u2014
defined as temporal correlation between electrical activity of different brain regions \u2014 to
effective connectivity\u2014defining causal relationships between functional activity of different
brain areas. Cortical areas of the brain physically linked by tracts of white matter fibres
are known to exhibit a more coherent functional synchronization than areas which are not
anatomically linked, but the absence of physical links between two areas does not imply a
similar absence of functional correspondence. Development and ageing, but also structural
modifications brought on by malformations or pathology, can modify the relation between
structure and function.
The aim of my PhD work has been to further investigate the existing relationship between
structural and functional connectivity in the human brain at different ages of the human
lifespan, in particular in healthy adults and both healthy and pathological neonates and
children. These two \u2019categories\u2019 of subjects are very different in terms of the analysis
techniques which can be applied for their study, due to the different characteristics of the data
obtainable from them: in particular, while healthy adult data can be studied with the most
advanced state-of-the-art methods, paediatric and neonatal subjects pose hard constraints to
the acquisition methods applicable, and thus to the quality of the data which can be analysed.
During this PhD I have studied this relation in healthy adult subjects by comparing structural
connectivity from DWI data with functional connectivity from stereo-EEG recordings
of epileptic patients implanted with intra-cerebral electrodes. I have then focused on the
paediatric age, and in particular on the challenges posed by the paediatric clinical environment
to the analysis of structural connectivity. In collaboration with the Neuroradiology
Unit of the Giannina Gaslini Hospital in Genova, I have adapted and tested advanced DWI analysis methods for neonatal and paediatric data, which is commonly studied with less
effective methods. We applied the same methods to the study of the effects of a specific brain
malformation on the structural connectivity in 5 paediatric patients.
While diffusion weighted imaging (DWI) is recognised as the best method to compute
structural connectivity in the human brain, the most common methods for estimating functional
connectivity data \u2014 functional MRI (fMRI) and electroencephalography (EEG) \u2014
suffer from different limitations: fMRI has good spatial resolution but low temporal resolution,
while EEG has a better temporal resolution but the localisation of each signal\u2019s
originating area is difficult and not always precise. Stereo-EEG (SEEG) combines strong
spatial and temporal resolution with a high signal-to-noise ratio and allows to identify the
source of each signal with precision, but is not used for studies on healthy subjects because
of its invasiveness.
Functional connectivity in children can be computed with either fMRI, EEG or SEEG,
as in adult subjects. On the other hand, the study of structural connectivity in the paediatric
age is met with obstacles posed by the specificity of this data, especially for the application
of the advanced DWI analysis techniques commonly used in the adult age. Moreover, the
clinical environment introduces even more constraints on the quality of the available data,
both in children and adults, further limiting the possibility of applying advanced analysis
methods for the investigation of connectivity in the paediatric age.
Our results on adult subjects showed a positive correlation between structural and functional
connectivity at different granularity levels, from global networks to community structures
to single nodes, suggesting a correspondence between structural and functional organization
which is maintained at different aggregation levels of brain units. In neonatal and
paediatric subjects, we successfully adapted and applied the same advanced DWI analysis
method used for the investigation in adults, obtaining white matter reconstructions more
precise and anatomically plausible than with methods commonly used in paediatric clinical
environments, and we were able to study the effects of a specific type of brain malformation
on structural connectivity, explaining the different physical and functional manifestation
of this malformation with respect to similar pathologies. This work further elucidates the
relationship between structural and functional connectivity in the adult subject, and poses
the basis for a corresponding work in the neonatal and paediatric subject in the clinical
environment, allowing to study structural connectivity in the healthy and pathological child
with clinical data
Tractographie adaptative basée sur la microstructure pour des analyses précises de la connectivité cérébrale
Le cerveau est un sujet de recherche depuis plusieurs décennies, puisque son rôle
est central dans la compréhension du genre humain. Le cerveau est composé de
neurones, où leurs dendrites et synapses se retrouvent dans la matière grise alors que
les axones en constituent la matière blanche. L’information traitée dans les différentes
régions de la matière grise est ensuite transmise par l’intermédiaire des axones afin
d’accomplir différentes fonctions cognitives.
La matière blanche forme une structure d’interconnections complexe encore dif-
ficile à comprendre et à étudier. La relation entre l’architecture et la fonction du
cerveau a été étudiée chez les humains ainsi que pour d’autres espèces, croyant que
l’architecture des axones déterminait la dynamique du réseau fonctionnel.
Dans ce même objectif, l’Imagerie par résonance (IRM) est un outil formidable
qui nous permet de visualiser les tissus cérébraux de façon non-invasive. Plus partic-
ulièrement, l’IRM de diffusion permet d’estimer et de séparer la diffusion libre de celle
restreinte par la structure des tissus. Cette mesure de restriction peut être utilisée
afin d’inférer l’orientation locale des faisceaux de matière blanche. L’algorithme de
tractographie exploite cette carte d’orientation pour reconstruire plusieurs connexions
de la matière blanche (nommées “streamlines”).
Cette modélisation de la matière blanche permet d’estimer la connectivité cérébrale
dite structurelle entre les différentes régions du cerveau. Ces résultats peuvent être
employés directement pour la planification chirurgicale ou indirectement pour l’analyse
ou une Ă©valuation clinique.
Malgré plusieurs de ses limitations, telles que sa variabilité et son imprécision, la
tractographie reste l’unique moyen d’étudier l’architecture de la matière blanche ainsi
que la connectivité cérébrale de façon non invasive.
L’objectif de ce projet de doctorat est de répondre spécifiquement à ces limitations
et d’améliorer la précision anatomique des estimations de connectivité structurelle.
Dans ce but, nous avons développé un algorithme d’optimisation globale qui exploite
les informations de micro et macrostructure, en introduisant une procédure itéra-
tive qui utilise les propriétés sous-jacentes des tissus pour piloter la reconstruction
en utilisant une approche semi-globale. Ensuite, nous avons étudié la possibilité
d’adapter dynamiquement la position d’un ensemble de lignes de courant candidates
tout en intégrant le préalable anatomique de la douceur des trajectoires et en adap-
tant la configuration en fonction des données observées. Enfin, nous avons introduit
le concept de bundle-o-graphy en mettant en œuvre une méthode pour modéliser des
groupes de lignes de courant basées sur le concept que les axones sont organisés en
fascicules, en adaptant leur forme et leur Ă©tendue en fonction de la microstructure
sous-jacente.Abstract : Human brain has been subject of deep interest for centuries, given it’s central role in controlling and directing the actions and functions of the body as response to external stimuli. The neural tissue is primarily constituted of neurons and, together with dendrites and the nerve synapses, constitute the gray matter (GM) which plays a major role in cognitive functions. The information processed in the GM travel from one region to the other of the brain along nerve cell projections, called axons. All together they constitute the white matter (WM) whose wiring organization still remains challenging to uncover. The relationship between structure organization of the brain and function has been deeply investigated on humans and animals based on the assumption that the anatomic architecture determine the network dynamics. In response to that, many different imaging techniques raised, among which diffusion-weighted magnetic resonance imaging (DW-MRI) has triggered tremendous hopes and expectations. Diffusion-weighted imaging measures both restricted and unrestricted diffusion, i.e. the degree of movement freedom of the water molecules, allowing to map the tissue fiber architecture in vivo and non-invasively. Based on DW-MRI data, tractography is able to exploit information of the local fiber orien- tation to recover global fiber pathways, called streamlines, that represent groups of axons. This, in turn, allows to infer the WM structural connectivity, becoming widely used in many different clinical applications as for diagnoses, virtual dissections and surgical planning. However, despite this unique and compelling ability, data acqui- sition still suffers from technical limitations and recent studies have highlighted the poor anatomical accuracy of the reconstructions obtained with this technique and challenged its effectiveness for studying brain connectivity. The focus of this Ph.D. project is to specifically address these limitations and to improve the anatomical accuracy of the structural connectivity estimates. To this aim, we developed a global optimization algorithm that exploits micro and macro- structure information, introducing an iterative procedure that uses the underlying tissue properties to drive the reconstruction using a semi-global approach. Then, we investigated the possibility to dynamically adapt the position of a set of candidate streamlines while embedding the anatomical prior of trajectories smoothness and adapting the configuration based on the observed data. Finally, we introduced the concept of bundle-o-graphy by implementing a method to model groups of streamlines based on the concept that axons are organized into fascicles, adapting their shape and extent based on the underlying microstructure.Sommario : Il cervello umano è oggetto di profondo interesse da secoli, dato il suo ruolo centrale
nel controllare e dirigere le azioni e le funzioni del corpo in risposta a stimoli
esterno. Il tessuto neurale è costituito principalmente da neuroni che, insieme ai dendriti
e alle sinapsi nervose, costituiscono la materia grigia (GM), la quale riveste un
ruolo centrale nelle funzioni cognitive. Le informazioni processate nella GM viaggiano
da una regione all’altra del cervello lungo estensioni delle cellule nervose, chiamate
assoni. Tutti insieme costituiscono la materia bianca (WM) la cui organizzazione
strutturale rimane tuttora sconosciuta. Il legame tra struttura e funzione del cervello
sono stati studiati a fondo su esseri umani e animali partendo dal presupposto che
l’architettura anatomica determini la dinamica della rete funzionale. In risposta a
ciò, sono emerse diverse tecniche di imaging, tra cui la risonanza magnetica pesata
per diffusione (DW-MRI) ha suscitato enormi speranze e aspettative. Questa tecnica
misura la diffusione sia libera che ristretta, ovvero il grado di libertĂ di movimento
delle molecole d’acqua, consentendo di mappare l’architettura delle fibre neuronali
in vivo e in maniera non invasiva. Basata su dati DW-MRI, la trattografia è in
grado di sfruttare le informazioni sull’orientamento locale delle fibre per ricostruirne
i percorsi a livello globale. Questo, a sua volta, consente di estrarre la connettivitĂ
strutturale della WM, utilizzata in diverse applicazioni cliniche come per diagnosi,
dissezioni virtuali e pianificazione chirurgica. Tuttavia, nonostante questa capacitĂ
unica e promettente, l’acquisizione dei dati soffre ancora di limitazioni tecniche
e recenti studi hanno messo in evidenza la scarsa accuratezza anatomica delle ricostruzioni
ottenute con questa tecnica, mettendone in dubbio l’efficacia per lo studio
della connettività cerebrale. Il focus di questo progetto di dottorato è quello di affrontare in modo specifico
queste limitazioni e di migliorare l’accuratezza anatomica delle stime di connettivitĂ
strutturale. A tal fine, abbiamo sviluppato un algoritmo di ottimizzazione globale che
sfrutta le informazioni sia micro che macrostrutturali, introducendo una procedura
iterativa che utilizza le proprietĂ del tessuto neuronale per guidare la ricostruzione utilizzando
un approccio semi-globale. Successivamente, abbiamo studiato la possibilitĂ
di adattare dinamicamente la posizione di un insieme di streamline candidate incorporando
il prior anatomico per cui devono seguire traiettorie regolari e adattando
la configurazione in base ai dati osservati. Infine, abbiamo introdotto il concetto
di bundle-o-graphy implementando un metodo per modellare gruppi di streamline
basato sul concetto che gli assoni sono organizzati in fasci, adattando la loro forma
ed estensione in base alla microstruttura sottostante
Reduced structural connectivity between left auditory thalamus and the motion-sensitive planum temporale in developmental dyslexia
Developmental dyslexia is characterized by the inability to acquire typical
reading and writing skills. Dyslexia has been frequently linked to cerebral
cortex alterations; however recent evidence also points towards sensory
thalamus dysfunctions: dyslexics showed reduced responses in the left auditory
thalamus (medial geniculate body, MGB) during speech processing in contrast to
neurotypical readers. In addition, in the visual modality, dyslexics have
reduced structural connectivity between the left visual thalamus (lateral
geniculate nucleus, LGN) and V5/MT, a cerebral cortex region involved in visual
movement processing. Higher LGN-V5/MT connectivity in dyslexics was associated
with the faster rapid naming of letters and numbers (RANln), a measure that is
highly correlated with reading proficiency. We here tested two hypotheses that
were directly derived from these previous findings. First, we tested the
hypothesis that dyslexics have reduced structural connectivity between the left
MGB and the auditory motion-sensitive part of the left planum temporale (mPT).
Second, we hypothesized that the amount of left mPT-MGB connectivity correlates
with dyslexics RANln scores. Using diffusion tensor imaging based probabilistic
tracking we show that male adults with developmental dyslexia have reduced
structural connectivity between the left MGB and the left mPT, confirming the
first hypothesis. Stronger left mPT-MGB connectivity was not associated with
faster RANnl scores in dyslexics, but in neurotypical readers. Our findings
provide first evidence that reduced cortico-thalamic connectivity in the
auditory modality is a feature of developmental dyslexia, and that it may also
impact on reading related cognitive abilities in neurotypical readers
Locally Estimated Hemodynamic Response Function and Activation Detection Sensitivity in Heroin-Cue Reactivity Study
INTRODUCTION: A fixed hemodynamic response function (HRF) is commonly used for functional magnetic resonance imaging (fMRI) analysis. However, HRF may vary from region to region and subject to subject. We investigated the effect of locally estimated HRF (in functionally homogenous parcels) on activation detection sensitivity in a heroin cue reactivity study.
METHODS: We proposed a novel exploratory method for brain parcellation based on a probabilistic model to segregate the brain into spatially connected and functionally homogeneous components. Then, we estimated HRF and detected activated regions in response to an experimental task in each parcel using a joint detection estimation (JDE) method. We compared the proposed JDE method with the general linear model (GLM) that uses a fixed HRF and is implemented in FEAT (as a part of FMRIB Software Library, version 4.1).
RESULTS: 1) Regions detected by JDE are larger than those detected by fixed HRF, 2) In group analysis, JDE found areas of activation not detected by fixed HRF. It detected drug craving a priori regions-of-interest in the limbic lobe (anterior cingulate cortex [ACC], posterior cingulate cortex [PCC] and cingulate gyrus), basal ganglia, especially striatum (putamen and head of caudate), and cerebellum in addition to the areas detected by the fixed HRF method, 3) JDE obtained higher Z-values of local maxima compared to those obtained by fixed HRF.
CONCLUSION: In our study of heroin cue reactivity, our proposed method (that estimates HRF locally) outperformed the conventional GLM that uses a fixed HRF
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